The etiology of IBS is multifactorial, it may be caused due to alterations in gut motility, small-bowel bacterial overgrowth, microscopic inflammation, and visceral hypersensitivity. some time acute gastro intestinal infection may also cause IBS. till today there is no treatment is available to permanently cure IBS, but several alternative therapy is proposed which includes usage of probiotics bacteria, these bacteria can alter the intestinal microbiota positively. probiotic bacteria includes Lactobacillus spp. and Bifidobacteria spp. are majorly used as a beneficial therapy.. recomended doses of beneficial bacteria is 10 billion to 100 billion per day. some other practices such as yoga, accupuncture also used to overcome IBS..

Hi,

I think, disturbances in intestinal flora might be a cause but not the only cause.

Marimuthu, I agree

It is a multifactorial disease; intestinal bacterial may be a factor for the development.

I agree with previous speakers about a complex, multifactorial etiology , e.g. the brain-gut model. To cope with IBS, there is growing support for CBT as an effective treatment, but yes, less so for treatment for physiological symptoms and course.

Mostly by, Irregular Bowel irritation and Psychological origin only.

This type of case,the patient feels,

1. the Urgency to drain the fecal matters immediately after In taking.

.2. If Upper GUt may stimulated, followed by Colon must reacted immediately.

3. Think that: its by bacteria or any cause, thy why they didnt cure IBS.

4. Absolutely Traditional system of Medicine can able to manage this..,

Best another Pscycological example:

The small child while going to School, the parents gave food hurrily, and immediatly the child said, i need to go toilet. ??????????

Conclu: While hurring, the unpper gut reacted fast, at the same thime, child also having School fear. By all combinationation it looks like IBS...

Many studies have suggested that probiotics are effective in the treatment of IBS. http://www.ncbi.nlm.nih.gov/pubmed/?term=irritable+bowel+syndrome+probiotics

bacteria over-growth may start anew episode of IBS but the predisposition factor should be exit ,IBS still unknown,probiotics has not evidence in this concern

There is reasonable evidence of a modest benefit of probiotics in IBS. Given their impressive safety profile, a trial of probiotics is certainly worth considering. However, it is unlikely that probiotics will be beneficial for all patients with IBS.

Another factor that has not been considered in this forum is the visceral sensitiviy which is increased in patients with IBS (threeshold painful rectal distention and electrostimulation). Moreover, other factors may be: increased intestinal permability and colonic mucosal micro-inflammation (increased mast cells). Patients with IBS have increased modulation of neural response to visceral stimuli demonstrated by MRI and PET. Increased mast cells-nerve contacts have been seen at electron microscopy. A trial with probiotics must take into account possible effects on these factors. My doubt are: what probiotic? what dose? what kind of patients?

If you have not done so already, read the Wikipedia article on this topic. It is comprehensive and includes ca. 125 literature citations.

https://en.wikipedia.org/wiki/Irritable_bowel_syndrome

This is an excellent discussion of the topic, but I do not understand where it counteracts what I reported as some hypotheses that are found in the most recent literature and may play a role in the origin of IBS.

I agree with the probiotics (acidophilus) approach to rebuild upper intestinal flora, but also need to bring in today's absence of the stomach acid barrier that normally keeps a lot of the really bad bacteria from getting past the stomach. Likewise, the lack of stomach acid and dietary changes have added a great deal more time to breakdown the food into the needed bolus so that the pyloric sphincter can open as it should in a timely fashion. Of course, this is a regional issue especially true of the United States and its debauched and overprocessed food supply, but I suspect is affecting every nation that is doing likewise to their food suppy. I am attaching one of my lecture monographs (in English and in Spanish) that might be helpful in this discussion.

Thank you for the remark of the stomach acid barrier role in the IBS development, Dr.Chartland, but this should mean that IBS is not more that SIBO underestimated.

Besides, your link contains a page in Spanish only. Is that all the lecture?

I should like to emphasize the remark of Andrey Borodach. The role of microbiota in intestinal and extra-intestinal disorders is a fascinating topic with promising and unexpected possibilities of development in the next future. However, it is known that the reduction of acid production in the stomach (PPI prolonged assumption and not only) increases SIBO development and SIBO symptoms, which as well as lactose malabsorption often overlap with that of IBS. So, I should clinch that the problem at the moment is very complex and, at the best of current evidences, cannot be explained by a single microbial deregulation. Moreover, "the probiotic therapy" of IBS has not pointed out and even its potential bases have to be discussed. A final provocation: what therapeutic probiotic regimen do you suggest to treat IBS, which bacterial strains, which dose, how long? All unanswered questions, it seems to me. So new suggestions from research and clinical trials are welcome! And what do you think about a trial of "microbiota transplantation"?

Andrey, I had uploaded first the English version, then the Spanish. I will provide the English again here. It is a condensed monograph that was a handout for the lecture on GERD, and really quite basic, but distilling some of the harder truths of the wrongness of today's practice of treatment for acid reflux that has brought so many unintended consequences to the public health in the US. I might add here that our observations in every case of IBS examined in our clinic also had a clear mind/body component (anxiety, OCD, anorexia, etc.) and usually traced back to earliest childhood, sometimes to premature birth. So the bacterial component of which Geir speaks is usually, in our thinking, a secondary factor arising out of mistreatment of the primary psychological/emotional aspects.

I might add that in our view every IBS patient should be placed on a good acidophilus, particularly one that is enteric in delivery (which most forms on the market are not enteric). In doing so, we do not look upon this as an end-all answer to the problem, but definitely a protective measure. The presence of thrush (candida) usually accompanies most of the cases we see, which is telling in terms of imbalance in upper intestinal flora.

Thank you, Dr.Chartrand, for the post about acid reflux, I downloaded it successfully and have read it. This is a sort of 'must know' for anyone practitioner. Thank you again.

Futher, at second, gentlemen, I am afraid being misunderstood a little. What I would like to say is that if SIBO documented to develope DUE to the chronic atrophic gatritis or gastric hypacidity of other kind (for example, due to a prolonged PPI intake), it is NOT the IBS by definition. It is just what it is, in other words, the atrophic gastritis consequences and should be considered and treated as such.

Whether or not the Irritable Bowel Syndrome itself can lead eventfully to the SIBO syndrome development, it is the most intriguing question, either from a practical point of view, and from academic one, and from didactic one as well. Whoever knows this, help us, share with us, highly estimated colleagues.

What is of highly interest also for me as a surgeon, is whether or not (and so on) does the fulminant SIBO develop during course of the ileus, mechanical small bowel obstruction, and 'gross' peritonitis (if one remember the 'cups' of gas in the distended small bowel loops). To the best of my knowledge, I could not find any data on these topics. Meanwhile, it is plausible that the answer will be worth its weight of gold for the morbidity and mortality decreasing in these groups of patients.

May I suggest reading this very recent article from Australia. This is becoming very popular in Europe too. It is related to bacterial metabolism of small non absorbed carbohydrates.

Gastroenterology. 2013 Sep 25. pii: S0016-5085(13)01407-8. doi: 10.1053/j.gastro.2013.09.046. [Epub ahead of print]

A Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome.

Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG.

I do believe that we should look into the causes of IBS to assess whether it can be prevented. For example, in about 10-20% of case of IBS there is an association with AGE. In this case, definitely the distortion of the intestinal microflora (dysbiosis) with upper small intestine harboring abnormal counts of nonbidifidogenic bacteria and the large intestine having a reduced abundance of bifidogenic bacteria due to the dynamics of the diarrhea may contribute to the development of IBS in some patients. Thus, perhaps, the treatment of AGE needs to be modified to prevent IBS.

To carry Francisco's insight a bit further, we find in our region that prescription medication is a driver in older adult IBS. Whether it is the meds for hypertension (often stacked onto each other) or statins for hyperlipidemia or long term prednisone and opioid pain killers, these ALL upset the digestive process of the patients. The majority of older adults that come to our clinic come with a long list of medications and multiple digestive issues. The answer, always, is to get to the underlying causes of their chronic conditions so that medications are not needed and to ask their physician to help them wean off the side-effect laden medications that are at root of a majority of their remaining health issues. Polypharmacy has created whole new pathologies in the US and is getting worse with every taxpayer-financed promotional campaign to get more and more Americans onto health-compromising medications. It is a serious problem and deserves honest discussion despite entrenched vested interests. We all know that digestion and other metabolic functions suffer efficiency with aging in general, and the answer is not more medications to superficially treat uncountable symptoms, but treatment modalities to get to underlying issues. Then, almost spontaneously, we see digestive issues improve dramatically.

Rome II diagnostic criteria for the IBS include:

12 weeks of abdominal discomfort for the last year on the background at least 2 of the 3 criteria:

1) relieved with defecation;

2) onset associated with a change in frequency of stool;

3) onset associated with a change in form, etc., of stool

Criteria recommended for exclusion of the IBS:

1) worsening with mensis, and other ginecology-related signs;

2) fever, rectal bleeding, and weight loss;

3) abdominal examination reveals no abnormality;

4) no 'major' abnormality in the large bowel structure.

[Thompson WG, et al / Functional bowel disorders and functional abdominal pain // Gut 1999;45(Suppl II): p.1144].

It is evidently enough that this definition of the IBS is to include a vast variety of pathological conditions produced by a myriad of causes. It should necessarily include mild and moderate forms of the SIBO (without signs of heavy enteritis and/or hepatitis/cirrhosis), a vague and not circumscribed definitely array of neurological disorders of the intestine itself and extraintestinal as well, and some dietary peculiarities, and being altered by the MALT current condition, so being depended from another large group of inner and environmental factors including wheather, water, climate.... And so on, and so on.

Secondly, the Rome criteria and discription are rather loose so that some private questions remained uncertain. For example, what does mean a passage 'abdominal examination reveals no abnormality'? What kind of examination was meant? What is a definition for 'abnormality'? If the gallbladder was removed several years ago, should it be taken as 'abnormality', or not? Or the appendix removed? Is the atrophic gastritis an 'abnormal' enough in this context? And 'subatrophic'? And further, and further, till infinity.

To conclude:

1) the IBS, by definition, is not else than a huge and extremely inhomogeneous collection of quite different conditions taking together due to chronic abdominal pain and stool habit disorders. So, nor its diagnostics, neither treatment of any kind cannot be identical.

2) treatment modalities may include probiotics and other methods for the SIBO correction, if documented.

3) The IBS conception warrants further investigations to become less amorphous entity.

4) Thank you, Dr. Edwards, for that interesting reference! It is what a physician ought to be awared of, at any rate.

As for non-absorbed low-molecular carbohydrates raising in Aurstralia and Europe practice, why not, especially in case of mild SIBO syndrome? It has been noticed long ago, that persons that shew a shewing gum with xylitol or sorbitol obtained also good teeth, excellent mood, and, seemingly, perfect bowel movements. The frequenter gum one takes, the less the intestine irritates.

It is now accepted that IBS is the peripheral manifestation of a central phenomenon i.e. brain-gut interaction, but we do believe that many factors have a role. One of these important factors is the disturbance of bacterial flora and the evidence for this came from different studies showing disturbances of the composition of bacterial flora in these patients as well as improvement of lower GI symptoms with the use of probiotics and some antibiotics.

Probiotics and Prebiotics (small non absorbed carbohydrates, I think) have been used in clinical trials for IBS treatment as well as in the clinical practice. The results are generally satisfactory. However, even placebo is able to improve IBS symptoms as well as other class of drugs (antispasmodics, antidepressants, herbal compounds, fiber-based nutritional supplements and surely I am forgetting some others). My idea is that IBS is a too complex entity, in which a role of intestinal bacterial flora may be relevant, but also not the only one. Moreover, clear details about bacterial alterations and their adjustements need to be still clarified. All reported literature is very interesting, but each paper is a small piece to build a large mosaic.

Yes, Ierardi, placebo does a remarkable job on some individual IBS sufferers, most often in cases of anxiety and trait personality in our observation. In such cases, counseling can be most effective. In modern guts today, where upper intestinal pH rarely reaches pH 12.0 and stomach pH is to dip to pH 1.2, though, the problem takes on distinct attributes that are correctible primarily by diet, namely non-pharmaceutical but nutritional approaches. I would venture to say from observation that diet is key to perhaps 90% of cases of IBS, but standard therapeutic practices today rarely regard this and so continues to look onward for the magic pill that never brings mere symptomatic relief without considering the significant unintended consequences in its wake. To us, getting to core causes should always be the long term goal.

Likewise, Mohamed makes a good point with the bacterial flora aspect, which should be, in reality, the favorable end desired in any viable treatment program. We could add the downward positioning of the Transverse Colon brought on by obesity and sedentary lifestyle. So many considerations that need looked at first before one would logically reach into the pharma tool kit.

Very good sentence. Until now, diet duggestions in IBS was based on a constant intake of fibers and water in order to maintain a constant volume of alimentary residual with the final aim to stimulate a slow and continuous bowel movement. According to your remark, it is possible that diet could be addressed to positively change intestinal flora and environmental condiions. This is a very fascinating hypothesis, may you indicate some practical indications?

Yes, for the past several years me and my colleagues have been looking at the pH sequence from the time one takes food into their mouth and the biochemical cascade that results through to salivary composition to esophageal movements to cardiac sphincter to desired pH to change chyme into bolus in the stomach (starting at whatever the acid dilution level is caused by taking in drink and food that enters the stomach) to break the chyme into an acceptable bolus and its level of composite pH (about pH 1.2) that triggers the syncronous release of bicarbonate from the pancreas and bile from the liver into the duodenum (and upper intestine) so that the pyloric sphincter can open.

Stopping at this point I must remark that we are seeing a marked lengthening of time that the food must stay in the "modern stomach" (circa 2000 onward) versus the stomach of 35 years ago (circa 1978 when the major changes in the food supply in the US really got underway). The ideal time period that food needs to be broken down in the stomach appears to be 20-25 minutes (about what it was for most people in 1978), but has increased to as much as 2 hours in 2013 in the US. Because the stomach acid is no longer there in sufficient quantities to signal the release of bicarbonate from the pancreas into the duodenum and thus open the pyloric sphincter.

Typically, at this point, several things occur: 1) there is too much food into the stomach that is not a true chyme upon entry through the cardiac sphincter to be efficiently broken down, 2) the cycle of acid secretion is interrupted, and 3) over-diluted (not just from too much food and drink at once, but also from the chemical makeup of the food--too much simple carbs, caffeine, toxins, over-processed food, etc.), thus, 4) breaking eliminating the acid barrier needed to kill the bad bacteria at that stage of digestion, and 5) not enough production of the bicarbonate in the pancreas--it takes about three hours between meals for bicarbonate to recharge. Overlaid with this metabolically is the larger continual pull into acidosis state via loss of efficiency in the Kreb's cycle throughout the body itself.

So, the cascade continues with not enough bile secreted from the liver to break down the entering fats, and not enough bicarbonate to raise the pH of the duodenum to pH 8.0 and consequently the upper intestinal environment to the ideal pH 12.0 before descending in pH as the process continues through the intestines and colon areas. Thus, this presents a marked challenge for food to nutrition synthesis in the upper intestine and interruptions in hydration and elimination thereafter.

Please, forgive the length of the above explanation--but the cascade, though clear in its sequence, is immensely complex and difficult to outline in a few words. This is just a broad outline. The larger problem we have today is the erroneous treatment sequence provided by the medical system in the US (and by extension other countries where the same approach is used), namely:

1) failure to look for, address, and counseling relative to underlying causes before prescribing medications, so that egregious eating and dietary habits can be changed by the individual,

2) immediate prescription (and by extension promotion of OTC self-prescription) of reflux medications that shut down the vital acid cycle in the body, so that there is no longer an acid barrier to kill bacteria and breakdown the food adequately (as well as an almost total loss of certain B vitamins) nor the necessary secretions from the pancreas to quickly raise the pH of the duodedum and upper intestine (and by extension the large intestine and colon),

3) creating invasions of bacteria (salmanella and e Coli, among myriad others, come to mind) and undigested proteins (lacking protease enzymes, etc.) that form the resulting bolus, and invasion of bad bacteria, undigested proteins lacking protease enzymes, and a large amount of other substances not safe for the upper intestine (food additives, toxins, food that cannot be broken down into wastes, etc.). I might note that we see a population that is starving for nutrients on one hand and rapidly becoming acidic and overweight on the other hand.

I could continue the cascade to show interruption of friendly bacterial flora needed to synthesize nutrition and determine waste, a vast reduction in intestinal pH causing rapid bone loss and a constant pull into cellular acidosis for the entire body. Hence, the food finds itself at a crossroads of sorts and utter chaos as to where to go and how to get there. What I just described is the folly of modern foods, eating habits, and medical response combined to bring us ever growing numbers of Celiac, Crohn's, IBS, IBD, stenosis of the pyloric sphincter, and oveactive vagus reflex in the stomach. The resulting milieu is regularly confused at the diagnostic level and unprectible at the prognostic level, thus rendering continued suffering and eventually turning to mismanaged crises. In future posts I will describe what we are finding is needed to correct this state at a public health level. Changes in how we view in basic eating habits, digestion, and food supply are key--not the more profitable system of endless tests that tell us little of value and drugs that make matters worse in the long run.

@Max, good point

Dr. Chartrand, the picture of digestion at work drawn by you is really profound, marvelous, and fascinating at the same time. On the other hand, the charges filed as to the modern food supply and medical system in the US (and almost everywhere else as well as far as I could imagine the modern ways of 'feeding and treating')... So, the charges are too heavy so that not to raise questions about materials and methods used in the very work of yours' that have made you to come at this dramatic a conclusion?

It is the first point to start with.

Thank you, Andrey.

I realize it may be a new concept to someone relative to effects of food supply etc. that it comes across somewhat dramatized. But researchers far more versed than I can attest to the dramatic rise in chronic disease in the US and literally all of them with whom I've associated trace it all back to dietary changes and changes in the food supply. The changes are uniquely American are that 90-95% of all fresh foods are irradiated, and are of the GMO, degerminated variety. On the non-fresh side, overprocessing, food additives, toxic synthetic nutrition, and modern cooking methods (microwaving comes to mind) are most suspect. The rate of chronic disease is tracking closely with the loss of truly organic foods in our nation.

I am traveling for the next week so will have to give you a partial answer, but on the biochemistry and neurophysiology that I outlined above, that is fairly straightforward and common knowledge among those who understand digestion. The larger issue is allopathy's response to the rapid decline in efficiency of the modern digestive system by going after the easy to cover symptoms (acid reflux, for instance). For now, I offer a couple of references here to shed some light on this point:

Hofmann, A., and Mysels, K. (1992). Bile acid solubility and precipitation in vitro and in vivo: the role of conjugation, pH, and Ca2+ ions. Journal of Lipid Research. http://www.jlr.org/content/33/5/617.full.pdf

Thirteen Foods That Fight Acid Reflux (2013). http://www.health.com/health/gallery/0,,20440834,00.html.

Tips for Overcoming GERD (2013). http://www.gibay.com/articles/houston-acid-reflux-3-tips-to-overcoming-gerd.html.

As you know, when medical treatments interrupt the natural processes of human digestion to achieve a superficial effect a price is to be paid somewhere down the road, Consequently, all of the long-term drug treatments being used today and the recent dietary changes in the US have brought us rapidly incrasing chronic conditions in the population, such as diabetes mellitus II (13X per capita increase in the US since 1970), cardiovascular disease (17x increase by our estimates), and cancers of all kinds (25x increase). These have become the largest corporate enterprises in their own right with little incentive to dramatically undo what has been done. Who would wish vast increases in unemployment, financial loss, and eventual collapse of entire enterprises when the status quo assures increased market and profits by comparison?

So the clinics over here that see 20-30+ patients per doctor per hour, routinely make their primary income from endless clinical tests and medication scripts with surgeries when crises occurs. Little or no time is spent getting to underlying issues, or counseling for better health, such as ascertaining how much water the patient is drinking (Americans are chronically semi-dehydrated), how much caffeine and high fructose they are consuming (about 5x to 6x consumption increase since 1980), how they preapre their foods (most are microwaving over-processed food for the bulk of their diets), or how much of their diet is GMOs vs organic (GMOs comprise at least 90-95% of the US diet today).

Americans are also a terribly over-medicated society, more than any on Earth to my knowledge. Consequently, their rates of chronic disease leaves all other advanced nations in the proverbial dust. Now, whether I am agreed with or not on these immutable facts often determines on which side of the debate one stands in terms of livelihood. But these macro public health challenges are here just the same and it is a matter of perspective as to why. I just happen to subscribe to the school of thought that food is medicine and medicine should be food, and that acute disease (which is obviously more amenable to the medication route) is quite a different beast from chronic disease (which is often a reflection of one's dietary habits and lifestyle). I declare that modern medicine has made chronic conditions worse by treating them with acute medicine, instead of delving into root causes where they really should be headed. For instance, we have found that just addressing the hydration and resulting ADH issue, that perhaps half of all hypetension medication prescriptions could be avoided in the US.

The orthomolecular viewpoint, in my opinion, is a powerful one, and one that I am in hopes will be embraced by mainstream medicine someday. I realize that some health systems are doing a better job on these issues (perhaps yours is one), but ours is so deeply embedded with conflicts of interest that our even peered research has become suspect when the long view is considered.

Thanks again, Andrey, for a most stimulating question and I will try to revisit any lingering issues in the future.

Small is the world, and all the same is everywhere...

Habits are similar in developed countries and I agree with Andrey's sentence. A spontaneous question raises: which are the digestive problems of developing countries? Malnutrition firstly, but how feeding habits affect intestinal flora and may IBS be masked by other more severe problems? In conclusion, it is possible that a kind of nail drives out another.

Unfortunately, save the WHO reports of the most prominent infectious diseases edimiology, there is a prominent deficiency of publications from some of Southern contries both on therapeutic and surgical gastroenterology. From personal communications with surgeons those had or still have been working for years in rural areas of Equatorial Africa, I have learned that, for example, feeding habits in Equatorial Africa include predominantly vegetables ingestion and a very few of or no meat. These data can be considered by no way as nation-wide or, moreover, as racial, without any doubt. However, the gallstone disease or colon cancer are reported to be exclusively rare entities there.

On the other hand, the intussusception, mechanical obstruction of the small bowel by phytobezoars, and volvulus are everyday operations like those for gallstones and colon cancers in some Northern countries, and patients' age is mostly under 20-25 years. So, a thesis that a bowel microbial landscape is quite different in those with phytobezoars risque and those with the gallstone disease looks probable, as that of the IBS pathogenesis, if exists at all.

So that, the Rousseauists' call for 'backing to Nature' should be recommended to use but in a careful and gentle way, when and if only really appropriate, for, making a choice between a risque of death in the age of 15 and in that of 75, most of people evidently will choose the latter. What I wrote here, is not a conclusion or a statement, but an invitation only to discuss this opinion or share with more reliable data on this matter, if available.

Let's get back to basics. IBS is enigmatic because the gut, and specifically sensory afferent nerves (that communicate information from the enteric nervous system with the big brain) overreact. In other words they react to normal stimuli as if the gut is under attack. That may be distension from a gas bubble, food. So the stimuli are things that occur normally. The better question as to CAUSE is to understand why the nerves are so sensitive and react so often and so inappropriately. There is good evidence as it relates to protease activated receptors.

ANOTHER great question that needs to be asked is why does it present itself in different forms? There are 4 quadrants - constipation only, diarrhea only, oscillating diarrhea-constipation, and just pain and discomfort. Is this different subclasses of sensory nerves, location or different stimuli. The discussion has been rooted in therapy (which was not the question). One consideration many touch upon is calming the nerves from a barrage of activation but better gut health. That may take the form of more fiber (but do it slowly, remember CHANGE per se will cause an attack), better microflora. I disagree with Lactobacillus acidophilus as it is a transient bacteria (non-human resident but rather bovine), and the problem seems to be primarily large intestine not small. But probiotics are a good step but it will take time. I am aware of an amazonian medicinal plant from the croton species that I have published on its suppressive actions on sensory afferent nerves but not tested it clinically in IBS. I am aware of a start-up pharma/biotech company that is pushing for that application.

Ierardi, Andrey, and Mark, great input into the discussion! So many considerations and the first question that comes to mind is where do clinicians start in helping those with IBS, etc., in ovecoming their plight? Possibly the region matters more than any other consideration--per issues of bacterial, feeding habits, food supply, cultural disruptions, etc.). I have always subscribed to the researcher-practitioner model of clinical application, but within a pragmatic framework. Endless tests are costly and not feasible, but as the knowledge base with each clinician gorws, improved educated guesses can guide their recommendations for more positive outcomes.

Dear all, do you have experience (as me) of spontaneous positive outcomes? Is the the most suitable explanation based on the brain-gut axis or is there the possibility that concominant unexplored factors (perhaps changing intestinal flora) may have played a role? And is there a simple method to attempt to reach an explanation?

Personal perspective (not evidence based but maybe worthy of a little research). I've been an irritable bowel sufferer most of my adult life. I recently tried the 5:2 diet cutting out carbs for 2 days a week for the past 6 months and my IBS has completed resolved. Are we overloading the gut with carbs? is the period of low carb intake over the 2 days allowing the gut to in some way repair itself ? I don't know the answers but would be interested in learning if others have had the same experience!

Important to note that one must figure in the large intestine into discussions - carbs are largely absorbed in the small intestine, and the 4 quadrants of IBS (presentation forms) involve either diarrhea or constipation, and as such then you must include actions that are colonic. Changing carb quality, digestibility or quantity affects the microbiome - this is the basis of prebiotics and the anecdotes. The connection from bacteria to the symptoms is via immune mediators. The best driver shown to date are protease activated receptors, where the sensory afferent nerves that are activated register pain, discomfort and trafficking to the central nervous system to normal levels of gut dissension (experimentally done with balloons). So connecting bacteria, to immune activation to sensory neuronal hyper-responsiveness are the pathways that are being manipulated.

You can focus treatment efforts at each stage of this process and more than one may be best. There are tons of anecdotal evidence that changing the microbiome improves IBS presentation. The only known agent that calms sensory afferent nerves, reliably, is the amazonian medicinal plant called sangre de grade (Peru) or sangre de drago (Ecuador) which is a sap from various Croton species the most common being Croton lechleri. For access to this research check my publications - while not in IBS most are on sensory afferent nerves. An extract of this tradition medicine I believe has been approved as a drug in the USA, for the treatment of IBS-C.

Mark brings in the missing piece to our discussion (unless I missed someone else's contribution relative to the large intestine)--I had forgotten to mention the falling Transverse Colon condition that we see so commonly today and which receives so little attention in medical practice. Chronic dehydration, IBS, colitis, and a host of other conditions arising therefrom, even colon cancer in some (mis)treated cases. We have begun working on dietary, hydration, and exercise regimens to help overcome this aspect. In today's age of obesity, it is quite common to see the TC out of position in ways that contribute negatively to the larger picture, even presenting problems with sepsis, high proinflammatory cytokines, microbe imbalances, and problems that affect appetite, as well. What brave souls we have on this discussion string to try and parse out the vast complexities of this topic. Wishing you all a Happy & Joyous New Year!

Reading these interesting posts is almost like participating at an online course on IBS.

Many thanks to the “organizers” 

IMHO (here O = Office) I have to see many digestive disorders, and I have observed that the majority of the persons suffering of IBS suffers primarly from time-related stresses. People who has to work on imperative but shifting timings (like long-range drivers, medical personnel on rotational duties, seconds in the command-line of industrial/economical activities, etc). are not complaining about the disruption of their circadian or ultradian rhytms – but I am convinced that disturbances of their digestion is partly caused by these dysrhythmias. This epiphany made me to read more about the chronobiology of digestion, which made me to approach the treatament options having in mind also the aim to keep the synchronicity between the different compartments of digestion: 10-100 milisec rhythms in neurons, 1 sec rhythms in blood-supply, 1 minute rhytms in peristaltism, or 24h rhythm of gastric acid production (peak around midnight) or cortisol (peak early in the mornig, sub cantu galli)

It seems that the bandmaster of this orchestra of our body-parts is the rotation of the Earth which determines the circadian rhythm. As seasons are changing, the bandmaster slows or accelerate the rhythm. But if the changes are more abrupt, like in the case of shift-workers or in the case of the countries where winter\summer horaires are applied, that may cause chronobiological disturbancies and the digestive tract is usually the first which suffers.

So, practically, beside the excellent advices enumerated in the previous posts related to therapies of IBS I would add

- frequent and regular meals. Of course, is avoidable to perceive a meal as a supplimenatry stress-factor – but if someone really wants to get rid of the symptoms of this invalidating disease, she\he has to understand some basic relations between the interconnections of the subsystems of the digestive tract. A detailed discussion is anyway necessary: many of my patients were quite surprised to leave the office without a pill-prescription, although a diagnosis of chronic illness was established.

- good-quality, >7 hours sleep/day

- stress-management, physical exercise

Interesting take, Andras. Yes, I think too often in the modern world we tend to forget the season changes and need to adjust diet and eating habits. Having moved from Colorado (8500') to Arizona (1300' above sea level) two years ago, we have had to change our intake of proteins, eat considerably less red meat, much more fruits and vegetables lest we suffer acidosis states and worsened over all well-being. We see this a great deal with the huge population of winter visitors who come here and wonder why digestive and health problems ensue if they maintain the habits from the much more northerly climes from which they came. So these factors are vital for good health. Thank you.

In the past various cultures ate up to 5 or 6 helpings of fermented foods daily as this was an accepted form of food preservation. This is now missing from our western culture and we are missing out of all the beneficial bacteria's that are collectively called probiotics. Yes it take some preparation to make ginger beers, Kieffer, sourcrout, yoghurt's and the like but a little time is worth if for good health.

May I suggest that this interesting discussion would be even more fruitful if the participant share his/her own criteria for the IBS to diagnose or such a condition(s) that cut it off, sometimes at least?

Unfortunately, I could not find in available literature any mentions that the IBS patients been ever consulted with the proctologist, urologist, and gynecologist (so called 'trinity for the lower abdominal pain') to rule out, for example, a pelvic floor disorders, rectocele, etc. Is a general practitioner or gastroenterologist always quite sure that he/she did not miss something?

Besides, I did not find any data on the colonic-ileal reflux X-ray studies so that to exclude the absence of the oblique course of the terminal ileum into the ceacum. Seemingly, there are not reports of certain important gastrointestinal hormons' level in the IBS, especially, the motilin and IPP that have significant impact on the bowel motility.

At last, in spite of lots of information published worldwide, there are not prominent reports of the IBS and body mass index relations, the former and hypothalamic disorders, and so on.

As for the SIBO and IBS possible coexistence, there have been several artciles published recently:

PMID: 17631127

PMID: 20705664

PMID: 22315951

PMID: 23580243

that allow to hope that the starting question has not been closed completely yet by the 'psychoneurologists' and 'environmentalists'.

As for the promising intentions to use a chemical component of the Dragon's blood from a plant of Croton spp. aiming to decrease excitability of the (large?) bowel sensory neurons, they raise both hope, concern, and question to ask:

1) Having in mind that Il Sangre de Drago is supposed to be a medicine of every day and long basis, should one takes care of its mutagenecity? [PMID 15507372].

2) Why should not try a topical anesthetic like lidocaine, tetracaine, etc., in hard capsules or anithing of the kind, with the same aide, to provide a lower excitability of the bowel neurons? They are cheeper and more available, and have been studied by far as better.

Happy New Year, dear colleagues!

Dear Andrey, thank you for your lucid analysis which clarifies that the "mystery" of the Sangre de Drago, unknown to most of us, putting in relief an important aspect of the treatment of IBS: a long term treatment and, therefore, very safe. And it is true that we cannot just define IBS as a condition with symptoms and negative colonoscopy, including in a "big pot" a variety of conditions, such as disorders of the pelvic floor, and obstructed defecation. Moreover, I should like point out the little-publicized complications of haemorroidipexis after mico-resection of the rectal mucosa with Stapler technique, which in my experience are frequent and affect the quality of life of the patient so heavy.

Its interesting that accepted knowledge outside of the body... for example that carbs are sugar and sugar feeds bacteria... suddenly becomes so complicated when it is applied to the human animal. Also that food allergies cause inflammation which destroys villi, which leads to leaky gut and irritable bowel, yet food intolerances are so seldom looked at by medical doctors. Lastly water quality and quantity is seldom mentioned. Chlorine and fluoride both have long been documented as having very detrimental effects on the digestive tract and on the micro flora and fauna.

You are right on the button, Heather. We hear from veterinarian researchers that if we fed our pets what we eat we see the same diseases and much earlier death. They cannot tolerate processed food, microwaved food, sugar in refined state, additive chemicals we put in our drinking water, or really any of the snack food that people eat with little regard. Most disease is foreign to the healthy human body, and chronic disease particularly is a product of long term deficiencies and egregious consumption of substances not good for the body. And we have not even scartched the surface into the very relevant psychological, psychsocial. and trait personality aspects that very much affect the IBS topic of this question.

Yes, gut microbiota dysbiosis could be involved in a number os IBS cases. An increasing number of observations supports this hypothesis. We are investigating possible mechanisms of dysbiosis-related IBS. A decreased number of SCFA producing bacteria has been demonstrated. SCFA, in particular butyrate, are able to regulate visceral sensitivity, pain perception, gut motility, gut permeability, gut inflammatory state, etc. These findings support the possible use of selected probiotics (LGG, Saccharomyces boulardii, etc) or postbiotics ( commercially availabke butyrate formulation) for the treatment of this condition.

A "brief" synthesis of microbiota activities is summarized as follows.

Lactobacilli represent a Gram–positive, facultative anaerobic or microaerophilic rod-shaped class of bacteria belonging to Firmicutes phylum. In nature there are at least 60 species that constitute the most relevant part of the group of lactic acid-producing bacteria converting the lactose and other sugars into lactic acid by fermentation. Lactobacillus constitutes the 97% -98% of normal microbial intestinal flora and counteract the proliferation of other microbes keeping the environmental pH values around 5.

A first important function in which Lactobacilli play a relevant role is adhesion to enterocyte surface, thus enhancing the production of mucus and intestinal permeability. The role of lactobacilli in maintaining the intestinal barrier function is achieved by various mechanisms such as inducing mucus production, modulation of cytoskeletal, and tight junction protein phosphorylation, and preventing apoptosis of the intestinal epithelial cells. Mucin is important in maintaining barrier function because it forms a physicochemical protective barrier for the underlying intestinal epithelial cells and operates in the prevention of mechanical, chemical, enzymatic, and microbial damage of intestinal barrier and also restricts microbial invasion which follow bacterial adherence to mucosa[11]. Enhancement of epithelial barrier integrity by lactobacilli has been observed in both in vitro and in vivo models. In vitro experiments with selected It has been shown that Lactobacillus strains antagonize the adherence of enteropathogenic E. coli to human intestinal epithelial cells by the induction of intestinal mucin gene expression. Furthermore, mucin is known to inhibit bacterial translocation, and studies with L. casei LGG showed increased expression levels of mucin genes in a Caco-2 cell model. Expression of mucin genes, induced by lactobacilli, has been shown to be dependent on direct cell contact between L. plantarum and intestinal epithelial cells.

In Lactobacillus casei, a subgroup of surface proteins containing a specific proteic motif is recognized by its SrtA protein. SrtA cleaves surface proteins and anchors resulting products to wall proteoglycan (PG), thus incorporating these SrtA-dependent proteins on the microbial surface. In this way, the maintenance of barrier function, mucus production, and immunomodulation are guaranteed. In Lactobacillus reuteri, the same function is performed by two exclusive bacterial proteic products, i. e. Mucus binding protein (Mub) and Collagen binding proteins (CnBP).

Another important function played by Lactobacilli is the competition against pathogen strains. Possible explanations for this function is that they reduce the adherence of pathogen strains to intestinal mucosa. Lactobacilli bind to receptors that are expressed on epithelial cells linking pathogenic species, thus exerting a protection from the damage caused by pathogenic bacteria and preserving barrier integrity. For instance, L. rhamnosus R0011 and L. acidophilus R0052 inhibit infection of intestinal cells caused by exposure to E. coli by reducing bacterial adhesion and cytoskeletal rearrangements.

On the other hand, another function of Lactobacilli is the production of lactase by means of which they contribute to lactose digestion. Recently, three new genes were identified, encoding the respective enzymes: lactate dehydrogenase (LDH), adhE - Ldb1707 acetaldehyde dehydrogenase, and catabolite control protein A (ccpA-pepR1). It was observed that Lactobacillus delbrueckii UFV H2b20 cultured in different media had the surprising ability to catabolyze galactose, and to produce high amounts of its metabolite succinic acid.

A final observation may be pointed out on the complex modulation of immune system in which lactobacilli are involved. Lactobacili, indeed, are able to modulate immune responses of the host by interaction with the gastrointestinal mucosa. Microbe-associated molecular patterns (MAMP), are a complex of bacterial surface proteins that exhibit characteristic features, such as cell wall components [Lypolysaccharide (LPS), wall proteoglycans (PG) and lipoteichoic acids (LTA)][21,22]. MAMPs are able to bind pattern recognition receptors (PRR) which are receptors molecules that are expressed by many cell types such as immune cells, intestinal epithelial cells, and non-immune cells thus inducing a signaling cascade that ends in the production of cytokines, chemokines, and other effector molecules. The specific cross-talk between MAMPs with PRRs and the following induction of signaling pathways depends on the microorganism and the reactivity of the host, which play a simultaneous major role in maintaining both the effectiveness and homeostasis of intestinal epithelial barrier.

Actinobacteria represent a group of Gram-positive mostly aerobic bacteria, characterized by a filamentous shape. Sometimes they form branching filaments, which may resemble the mycelia of fungi, among which they were originally classified under the older name Actinomycetes. Similarly to Firmicutes, the other main group of Gram-positive bacteria, they have DNA with a high G+C-content, and some Actinomycetes species produce external spores. Among all bacterial species belonging to this phylum, Bifidobacteria are the most known and studied, due to the reason that Bifidobacteria are ubiquitous, endosymbiotic inhabitants of the gastrointestinal tract.

Bifidobacteria have been shown to influence intestinal functions similarly to Lactobacilli. Intestinal transit is modified by the use of probiotics, in particular Bifidobacteria. Several bacterial strains have demonstrated activity against diarrhoeas of various aetiologies, and, at this regard, several studies have demonstrated that probiotics accelerate transit time. For example, a double-blind, randomized, controlled study has shown that healthy women had shorter (P < 0.05) total colonic and sigmoid transit times following the ingestion of 375 g/day of a fermented milk containing yoghurt cultures plus Bifidobacterium animalis DN-173 010 for 10 days compared with the time for the bacterium-free product. Even the total amount of probiotic ingested affects transit time, since the effect was more marked with 375 g than 250 g/day (P < 0.05), as showed by Bugaut et al.

Bifidobacteria have an important role in maintaining the immune defense inducing the protection of host from infectious diseases and toxins. A Japanese working group showed a protective function of acetate produced by Bifidobacterium longum against enterotoxin by E. coli O157: when germ-free mice were orally inoculated with O157, they died within seven days after O157 infection. However, the mice survived when they were colonized seven days before O157 infection with Bifidobacterium longum subspecies: longum JCM 1217T (BL), infantis 157F (BF), or longum NCC 2705 (BN). On the other hand, a different species such as Bifidobacterium adolescentis JCM 1275T (BA), showed no probiotic effect and failed to prevent the death of mice induced by O157 infection under the same conditions. Authors explained this effect by quantifying the amount of short-chain fatty acids (SCFAs) such as formate and acetate in mice stools. The data showed that only the concentration of acetate was significantly higher in feces in the mice colonized with the preventive strains than in those with non-preventive ones.

Bifidobacteria are fundamental in pediatric age for human milk oligosaccharides (HMOs) metabolism. HMOs are minimally digested by the infant, so that a lack of this strain may negatively reflect the quality of digestion in children. In fact, infant-type Bifidobacteria utilize these soluble carbohydrate oligomers by convergent mechanisms. Bifidobacterium longum subspecies infantis efficiently metabolizes several small HMOs masses and possesses a large gene cluster and other loci dedicated to HMO metabolism. This hydrolytic capability broadens its oligosaccharide utilization, so that human breast milk results more digestible for the newborn, thus avoiding infantile colics.

Furthermore, Bifidobacteria are fundamental in preventing pouchitis, a typical complication that occurs following proctocolectomy and pouch reconstruction associated with ileoanal anastomosis in patients affected by ulcerative colitis (UC)[36]. The most convincing evidence of the clinical effect of probiotics in human inflammatory bowel diseases was generated by a small prospective, double-blind, placebo-controlled trial showing that a combination of eight probiotic bacteria including three strains of bifidobacteria (longum, breve and infantis) prevented relapse of chronic pouchitis after induction of remission by antibiotics. However, the maintenance of remission in UC is guaranteed only by common pharmacological treatment used for this condition, in combination with a mixture of different probiotic strains including Bifidobacteria (B. longum DSM 24736, B. breve DSM 24732, B. infantis DSM 24737), Lactobacilli (L. acidophilus DSM 24735, L. plantarum DSM 24730, L. paracasei DSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734) and Streptococci.

What do I want to demonstrate with this summary of main probiotics beneficial effects? Very interesting perspectives are linked to this "organ in the organ" which may be modified by external agents such as foods and drugs and it is presumably that its changes may change intestinal function. However, how much evidence-based data are available about the possibility of modifying intestinal microbiota in order to normalize intestinal functions?

Dr.Enzo,

Thank you for the most profound report of the intestinal microbiota!

However, what one could say about evidence-based studies about the possibilities to modify the intestinal microbiota, if each gram of the colon content contains up to several billions of CFU?! This huge number is far beyond possiblilities of modern mathematics, microbiology and DNA sequencing altogether. To the best of my knowledge, authors of few, very cost and longlasting studies of that kind investigated some 20-30 persons' stool microbiota, and extrapolated those data to the whole mankind that that is approximately 500 species (or 1000 more, from others sources):

Backhed F, Ley RE, Sonnenburg JL, et al. Host–bacterial mutualism in the human intestine. Science 2005;307:1915.

Eckburg PB, Bik EM, Bernstein CN, Purdom E, et al. Diversity of the human intestinal microbial flora. Science 2005;308:1635;

Dethlefsen L, Eckburg PB, Bik EM, Relman DA. Assembly of the human intestinal microbiota. Trends Ecol Evol 2006;21:517;

Moore WEC, Holdeman LV. Human fecal flora: the normal flora of 20 Japanese-Hawaiians. Appl Microbiol 1974;27:961;

Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev

Microbiol 1977;31:107.

Those are just the utmost prelimanary data, and researchers are seemingly at the very beginning of the very long road to go still. One billion of colony forming units means that there are 1000000000(!) (factorial billion, or a number I could not calculate) of possible variants of microbiota pattern in 1 g of the colon content. To compare, a usual code or lock has 6-8 variables only that is considered enough for them to be safe. Surely that the variants of the colon microbiota are not equal to each other, but, nevertheless, how to count the unnumerable and how to find out what a minority does not matter for the whole colon function, and which does?

Dear Andrey,

my agreement with you is complete. On the other hand, a sinilar concept I attempted to report in my answer of about 30 days ago: "Moreover, clear details about bacterial alterations and their adjustements need to be still clarified. All reported literature is very interesting, but each paper is a small piece to build a large mosaic." So the questions you raised are still uncompletely answered.

Thank you, I believe that everybody have noticed your post about that.

The Lactobacilli are essential for normal function of the human intestine without any doubt; and both kieffer and yoghurt , and the like are tasteful and highly needed products for the human being as well.

As everything, the Lactobacilli may contibute both to favourable and negative processes. For example, they may play a negative role in the immunocompromised patients. If overdosed as probiotics, they may cause the real acute enterocolitis.

Moreover, they produce the lactic acid that can act not only as an antiseptic for facultative pathogens as E.coli, etc,, but may damage the intestinal mucosa also causing a chemical (acidic) burn up to tissue necrosis. It would depend on its concentration and exposure time that in their turn depend on, for example, sugars level, etc. From this point of view, the acetic acid maybe even more agressive medium than the lactic one.

The lactic acid harmful effect on the teeth enamel is commonly known as the caries (produced by the Streptococci). The lactic acid is one of unoxidised completely metabolites that seemingly cause tissue fibrosis and destruction in the heart congestion disease (lower extremities ulcers, liver cirrhoses, etc). I have already asked questions about the lactic acid in the Researchgate, but they left without attention (Does anybody have data about colony-forming units of the Streptococci, on the skin or in the derma of Erysipelas patients? and Does a method exist of staining blocks for the lactate or acetate presence?)

Meanwhile, the simplest way to induce a ‘peptic’ ulcer is to inject the acetic acid into the gastric wall by a syringe that will cause a local tissue necrosis (as it was done by S.Okabe) so that to become ‘classic’ and most used in pharmacy an experimental model since the 60ths. According to that model, a ‘peptic’ ulcer occurs in a few days and will exist for several months and even years. Interestingly, it was reported that the relapses may occurr as well [Okabe S. & Amagase K. / An overview of acetic acid ulcer models. The history and state of the art of peptic ulcer research // Biol. Pharm. Bull., 2005; 28(8): 1321-1341]. Besides, S.Okabe wrote in the article that he tried first other medium as HCl, alcohole, ammonium, etc, but they DID NOT cause the stomach ulcer development in the rat! On the other hand, the lactic acid did.

These facts might shed some light on the IBS development as well, and - who knows! - even on those enigmatic matters as the inflammative bowel diseases' possible innate mechanisms. However, the chemical factors seem not fasionable enough these days...

A recent paper found that extreme animal diets that increase bile resistant bacteria in the colon do increase the risk for IBD. It was in one the nature group of journals. Will try to find it

Another thought on the IBD in case we have not brought that into the discussion: As the population's weight increases (and even in those who are not overweight but their abdominal muscles have deteriorated) we have a lot of adults with fallen transverse colons that prevent the back and forth movement of wastes from rectum back into the TC--this process can repeat itself a few times while sleeping, but if blocked because of sharp curvature from the TC lying too low in the abdomen, will cause IBD-like problems for the patient.

Precisely, but for this very case, the method of choice for treatment has to be quite different! Neither probiotics, neither local anaesthetics can make it better. Either physical execises for the abdominal muscles restoration+weight loss, or, for intractable patients, surgery is needed so that to cut the spleno-colonic ligament off and set the splenic flexure down, or a sort of. The former way is much preferrable and safe, but many patients would rather choose the latter, unfortunately.

Yes, Andrey, exercise for the abdominal muscles is precisely what we recommend, and the results are nothing less than stellar. For in the process of doing so, excessive weight it lost, and other systems in the body are improved, including diet and hydration.

Agreed completely.

There are extensive reviews discussing the role of bacteria in IBS. May I suggest you take a look at Simrem M (Gut 2013;62:159-76) and Salonen A (Microbiology 2010;156:3205-15) work? Hope it helps!

Excellent reference, Ferran. We have long suspected that these bacteria particularly affect the individual on a chronic basis because of the loss of acid barrier in the stomach combined with the loss of bacterial flora of the upper intestine and compromised immune response. This state reflects those whose bodies are in acidosis state and are taking acid reflux medications, eating mainly an irradiated, synthetically fortified, high carbohydrate processed diet. The cascade is quite clear yet ignored in the models for treatment that we currently see in practice.

A thorough review of the scientific literature led me to suspect that the cause of IBD and IBS is related to bacterial dysbiosis (infection via microorganism, injury, and or

imbalance), the cause of which may be multifactorial. If not, then why

are antibiotics sometimes used to treat IBD? Bacteria can cause ulcers

in the stomach, so why would they (& possibly viruses) not be capable of

doing so further down the gastrointestinal tract? Dr. Barry James Marshall,

was the Australian physician who won the Nobel Prize for showing that

the bacterium Helicobacter pylori is the cause of most peptic ulcers,

reversing decades of medical doctrine. The same may be true for IBD and IBS. It's not all in your head.

Borody's 2003 article reporting on a bacterial treatment that worked in 6 cases of ulcerative colitis. They simply used enemas and replanted the colon with bacteria from the gut of healthy fecal donor. The researchers wrote a decade ago, "Complete reversal of symptoms was achieved in all patients by 4 months post-HPI, by which

time all other UC medications had been ceased." Follow-up articles

by Borody (2011, 2013) on this treatment shows that the procedure is not a cure and

might have to be repeated. However, it does not involve the serious

side-effects of drugs or removal of the colon. I have attached a few articles on the

various ways people are implementing fecal transplants. What needs to be researched

is finding the best fecal transplant method possible for IBD and IBS. The latest unpublished news from Chicago is that fecal transplant has been used successfully in a Crohn's disease case.

Unfortunately, IBD research and funding is primarily for drugs to reduce symptoms

and not on the real cause, and therefore real treatment for IBD. Fecal transplant for IBD and IBS has been passed over for over a DECADE after Borody's first report. It is interesting to note that in light of finally potentially treating IBD with fecal transplant, the FDA, after years of allowing it to be used for Clostridium difficile, quickly declared it a "drug" in need of an IND prior to further use. After much objection, it then reversed its decision, but only for Clostridium difficile and not IBD. It appears that someone already knows that fecal transfer is the answer. The fact that people die from Crohn's or suffer through abdominal surgeries isn't enough to change this damaging trend.

Perhaps the current research and treatment focus will change in the right direction to help millions of patients. Perhaps you and your medical group can make a difference, especially if located outside of the United States. I pass the baton to you and others that can contribute to this medical breakthrough, and help reduce patient suffering.

No doubt that microbiote is involved as a cause or a a consquence.

However, the real cause is depression as stated Bockus, one century ago.

Search for bodillly and possible psychic features.

Digestive functional troubles and pain from mouth to anus: how to understand, treat and cure.*

Bernard Maroy, 04 May 2010"Open the eyes and you shall see"

Functional diseases, pain and irritable organs are poorly understood, and therefore treated with suboptimal results. In fact, they are studied individually although numerous publications confirm their association with other digestive and extra-digestive dysfunctions. These associations favor a common cause.

Deductive studies, starting with a symptom and trying to understand its mechanism, fail because the mechanisms are complex and also possibly because various mechanisms may cause the same consequences.

I follow an opposite, inductive way. As a hepatologist, I understand quickly that treating the consequences of alcohol was inefficient, unless alcoholism itself and its causes are taken into account. It became clear that depression was the most important mechanism of alcohol craving. I developed therefore, along 25 years, a diagnostic and therapeutic system.

Starting with coccygodynia, it appeared that bodily signs of depression were numerous, frequently evocative and even specific. The association with psychic classical signs, association of signs with each other and the simultaneous disappearance with antidepressants, led me to the following conclusion: depression is a neuro-biochemical syndrome with multi-systemic consequences. The reason this has been overlooked lies in the divergence between neuro-bio-chemical scientific evidence and the day-to-day practice and concepts of dichotomy between soul and body in a platonician point of view. Therefore, depression has been considered more and more as purely psychic, forgetting the concept of endogenous depression and bodily manifestations, formerly well known.

Diagnostic systems used in psychiatry are designed to be specific but fail to define non-depression. As a consequence they are not sensitive. The vast majority of functional digestive troubles appear to me to be the direct consequence of a neurological dysfunction. Cure by antidepressants has confirmed my point of view.

The reason the efficiency of antidepressants is overlooked in many studies lies in the inability to foresee the efficiency and optimal dosage of each medication. So, a given dose of a given molecule improves only part of the patient. If the medication is not tolerated, it is going to be inefficient: change it. Any molecule has a threshold dose (for example, 25 to 50 mg/d for tricyclics), below this dose there is no effect at all (but amitryptiline).

If the medication is efficient, effect increases with dosage until a maximum is reached (a variable from almost nothing to perfect equilibration of depression). In the latter case, carry on a minimum of 6 months before slowly tapering dosage, checking that no sign reoccurs. In the former, change the molecule and try again. Sometimes many medications are efficient; sometimes only one works.

I usually start with a tricyclic, mainly amoxapine 25mg then 50 mg. Tricyclics lead to dry mouth and constipation only when badly tolerated (change molecule) or supra-optimal dosage (taper dosage). I find the following to be the most efficient: clomipramine, imipramine, maprotiline, dosulepine, escitalopram, sertraline, fluvoxamine, and venlafaxine.

An optimal dosage leads frequently to partial effect. If you change the molecule you take the risk of a loss of efficiency if you need to use it again. If you don't change it is impossible to reach a perfect equilibration with this medication and moreover the result is frequently unstable. The logical solution is associating a second molecule to the former. Any risk of association is low in practice, especially if patients are informed and the doctor easy to reach.

I used to associate different classes of drug. The result of this is sometimes inhibition (1+1=0) or no effect at all (1+1=1) requiring change of the new molecule. However, the effect is sometimes additive (1+1=2), requiring the usual dosage of the new molecule, or it can be potentiating (1+1=3), requiring a low initial dosage of the new molecule. In associations I prefer as the second molecule: venlafaxine, mianserine and moclobemide (the latter with special caution).

With the present method, I am able to cure durably more than 90% of digestive functional troubles, together with associated signs: bodily, psychic and relational, as well. It is easy in 70% of cases, a bit difficult in 10%, difficult in a further 10% and problematic in the last 10%. Patients eventually do well as a whole, which is the real task of medicine.

Owing to my private practice, I am unable to perform studies necessary to prove this method. However, importance of results seems worth trying it. Risk of trying does not exist and potential efficiency is revolutionary. Remain taboo!

How to recognize depression in gastroenterological practice

Bernard Maroy, 15 January 2009This article details the conclusions I have reached after analyzing the somatic features of depression over 30 years.

I am a hepatologist who has practiced alcohology since 1979, and aims to understand and treat the main cause of relapsing liver disease. It quickly became clear that depression was a very important component of craving for alcohol. I, therefore, progressively developed algorithms of diagnosis and treatment.

I found that my criteria for depression were validated for several reasons:

Firstly, because they were statistically-associated with classical psychic signs of depression;

Secondly, some had been described previously;

And thirdly, because they disappeared following anti-depressive treatment, relapsing when this was stopped, and disappearing again with further treatment.

The first sign was coccygodynia and pain elicited by rectal touch. I succeed to publish this sign, but as I discovered many further signs it became too long to publish my studies, mainly because publications dealing with depression are rarely accepted. Moreover, it was boring to work hard to publish on out-dated features, when I was far ahead at that moment.

The basis of my work is that depression is a neuro-biochemical syndrome leading to multisystemic dysfuctions and. by no means, a merely psychic disease.

Suspecting depression?

Various digestive signs may be encountered. The most indicative feature is the intermittent appearance of symptoms with fluctuating intensity.

Starting with the mouth - dry or (rarely) excessive salivation, anomaly of taste (mainly abnormal spontaneous taste of any kind). Burning tongue or mouth without any local lesion.

Next the pharynx - globus, sensation of foreign body, frequently on a single side. Characteristic is improvement by or lack of deglutition effect.

Retrosternal pain is typically parasternal, often left-sided. It can realize (improvement after sipping water) a more or less typical reflux syndrome.

Epigastric pain is typically soon after a meal, or non-influenced by it as a heaviness associated with dyspepsia, early satiety, bloating and intestinal noises.

Nausea and vomiting are especially indicative, especially in the morning or when triggered by smell, as is travel sickness in adults. Nauseous reflex can be increased when brushing teeth, swallowing a tablet, during dentistry or upper endoscopy. This dyspepsia worsens with large fatty meals and during purgation for colonoscopy.

The liver can be tender - in part or whole - with a normal consistency, blood tests and ultrasound. It seems to me that depression can be a direct factor of fatty liver.

Depression is an important component of biliary-pancreatic sphincter dyskinesia.

At a colonic level, pain is frequent, usually diurnal, and alleviated by lying down. It is typical if burning or cold, as if owing to the quantitative or qualitative dysfunction of neuronal filters. Mucus can be wet or dry. Diarrhoea is typical if it is irregular, preceded by hard stools, urgent, of a low volume, decreases during the day, and occurs mainly during the morning and after meals, but rarely in the evening.

Constipation is typically propulsive with an empty rectum, even in case of urgency. Stools are rare, frequently small, due to hyperdigestion and difficult to pass, even if soft, owing to insufficient propulsion.

At the anal level, depression can cause various pains, more or less typical, from proctalgia fugax to coccygodynia. Depression is more frequent among fissure patients than among haemorrhoids or abscess patients. Localized pain can be due to peri-anal metameric syndrome, mainly S4.

How to confirm depression when it is suspected?

The first thing to do is to notice if presentation face mobility is normal and whether the hands are wet, then search for allodynia (pain elicited by a normally painless stimulation). Start on spontaneously painful locations, explore successively the different planes: skin (rarely), subcutaneous tissue by pinching or rolling; muscular tensing increases pain and deep planes like bones and insertions.

The search on elective locations: vertex, middle of sternum, xyphoid appendix, extremity of the last ribs, subcutaneous tissue and muscles of abdomen, lateral muscles by pinching, pubis, pubic spines, adductors of thigh, insertions of biceps on tibia and posterior spine joints. These pains can predominate over one or more hemi-dermatomes, frequently bilateral and asymmetric. It can be "all over" and then on the same side on face and body, contrary to organic pains. It seems to be due to an abnormal central treatment of normal afferent pain. Tickling or itching have the same value as pain. The first is a qualitative and the second a quantitative abnormality of central sensation modulation.

Ask the patient these questions:

Do you wake up during night, even for voiding?

Do you fall asleep easily?

Are you tired, especially in the morning?

Do you have difficulty starting the day?

Do you feel sleepy during day, especially after meals or driving?

How is your appetite?

Has your weight changed?

Do you have neuro-vegetative signs: instability, frequent voiding, itching, excessive sweating, spontaneous or evocated by exercise or eating, sexual, memory problems, nightmares?

Are you abnormally nervous, anxious, irritable, pessimistic? If possible, ask the patient's spouse.

Do you have any problem with alcohol?

Once these questions have been asked then decide whether a treatment is warranted. It depends of the perception of impediment by the patient and of his or her vision of the treatment.

This treatment is based on antidepressants adjusted by the "try and failure" method. It is better to start with a relatively low dosage, supra-liminar but infra-optimal (For example, 50 mg of tricyclics reached in a few days).

In the case of poor tolerance, stop the treatment because the medication is not going to be effective. If there is no effect, stop treatment for between 2 and 6 weeks, depending on the urgency of treatment, the number of medications tested and of earlier failures.

Wait until effect is maximal, then increase by steps until effect decreases. Hence, back to earlier dosage. If effect is only fair then begin again. If it is absolutely perfect, continue 6 months at full dosage, then diminish by prudent 2 months steps. Sometimes, a maintenance treatment is necessary.

If the result is good but not perfect, test an association with another antidepressant, preferably of another family, and so on…

Never forget that after stopping a medication its later effect will be frequently less. The curve dose-effect is not linear - flat for subliminar dosage, climbing if efficient and then declining over optimal dosage. These values vary from one patient to another.

Two illnesses can be associated, either because it causes depression or by chance because depression is very frequent all over the world.

Be careful before ascribing a recent pain to depression, even associated with an overlying allodynia.

Finally, the only way to make sure the exclusive responsibility of depression is to cure the patient with an effective treatment.

Further details about signs dealing with digestion and other systems, especially alcoholism, are detailed in English in my website bmaroy.free.fr and in my French language book La Dépression et Son Traitement: Aspects Méconnus. 2005 L’Harmattan, Paris.

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Digestive functional troubles and pain from mouth to anus: how to understand, treat and cure.*

Bernard Maroy, 04 May 2010"Open the eyes and you shall see"

Functional diseases, pain and irritable organs are poorly understood, and therefore treated with suboptimal results. In fact, they are studied individually although numerous publications confirm their association with other digestive and extra-digestive dysfunctions. These associations favor a common cause.

Deductive studies, starting with a symptom and trying to understand its mechanism, fail because the mechanisms are complex and also possibly because various mechanisms may cause the same consequences.

I follow an opposite, inductive way. As a hepatologist, I understand quickly that treating the consequences of alcohol was inefficient, unless alcoholism itself and its causes are taken into account. It became clear that depression was the most important mechanism of alcohol craving. I developed therefore, along 25 years, a diagnostic and therapeutic system.

Starting with coccygodynia, it appeared that bodily signs of depression were numerous, frequently evocative and even specific. The association with psychic classical signs, association of signs with each other and the simultaneous disappearance with antidepressants, led me to the following conclusion: depression is a neuro-biochemical syndrome with multi-systemic consequences. The reason this has been overlooked lies in the divergence between neuro-bio-chemical scientific evidence and the day-to-day practice and concepts of dichotomy between soul and body in a platonician point of view. Therefore, depression has been considered more and more as purely psychic, forgetting the concept of endogenous depression and bodily manifestations, formerly well known.

Diagnostic systems used in psychiatry are designed to be specific but fail to define non-depression. As a consequence they are not sensitive. The vast majority of functional digestive troubles appear to me to be the direct consequence of a neurological dysfunction. Cure by antidepressants has confirmed my point of view.

The reason the efficiency of antidepressants is overlooked in many studies lies in the inability to foresee the efficiency and optimal dosage of each medication. So, a given dose of a given molecule improves only part of the patient. If the medication is not tolerated, it is going to be inefficient: change it. Any molecule has a threshold dose (for example, 25 to 50 mg/d for tricyclics), below this dose there is no effect at all (but amitryptiline).

If the medication is efficient, effect increases with dosage until a maximum is reached (a variable from almost nothing to perfect equilibration of depression). In the latter case, carry on a minimum of 6 months before slowly tapering dosage, checking that no sign reoccurs. In the former, change the molecule and try again. Sometimes many medications are efficient; sometimes only one works.

I usually start with a tricyclic, mainly amoxapine 25mg then 50 mg. Tricyclics lead to dry mouth and constipation only when badly tolerated (change molecule) or supra-optimal dosage (taper dosage). I find the following to be the most efficient: clomipramine, imipramine, maprotiline, dosulepine, escitalopram, sertraline, fluvoxamine, and venlafaxine.

An optimal dosage leads frequently to partial effect. If you change the molecule you take the risk of a loss of efficiency if you need to use it again. If you don't change it is impossible to reach a perfect equilibration with this medication and moreover the result is frequently unstable. The logical solution is associating a second molecule to the former. Any risk of association is low in practice, especially if patients are informed and the doctor easy to reach.

I used to associate different classes of drug. The result of this is sometimes inhibition (1+1=0) or no effect at all (1+1=1) requiring change of the new molecule. However, the effect is sometimes additive (1+1=2), requiring the usual dosage of the new molecule, or it can be potentiating (1+1=3), requiring a low initial dosage of the new molecule. In associations I prefer as the second molecule: venlafaxine, mianserine and moclobemide (the latter with special caution).

With the present method, I am able to cure durably more than 90% of digestive functional troubles, together with associated signs: bodily, psychic and relational, as well. It is easy in 70% of cases, a bit difficult in 10%, difficult in a further 10% and problematic in the last 10%. Patients eventually do well as a whole, which is the real task of medicine.

Owing to my private practice, I am unable to perform studies necessary to prove this method. However, importance of results seems worth trying it. Risk of trying does not exist and potential efficiency is revolutionary. Remain taboo!

Author

Bernard Maroy MD

Contact details

Email: [email protected]

Bernard presents an excellent review of the dilemma of functional digestive disorders. I was particularly intrigued that his work is in hepatology as we are finding that livers that are tied up with endless antibody replicating as we see in hepatitis cases and others carrying uncountable diseases leave the liver too belabored to perform its more important work through bile, which sets off a number of metabolic and digestive cascades. We are not as thrilled with the SSRI/SNRI approach because we see it as interrupting the work of seratonin, which in our view is the most imporant managing/coordinating component of digestion. We find that in at least 70% cases and the literature bears this out as a conservative estimate that there in cases of clinical depression there is an underlying physical cause (often it is dental sepsis or unresolved but subclinical infections like keratosis obturans or ongoing sinus infections that are there but do not arise to clinical significance under the current standards). Another cause is heavy metals (most often lead) being released from the bones during acidosis states--we recommend eating a more organic diet, avoiding gluten, and to stop microwaving of food entirely in such cases--creating the neurosuppression that often manifests as mental depression. High caffeine intake, on the rise today, is another unsettling instigator of digestive issues, as are many if not most modern food additives. Investigating these and other causes and rectifying those, to me, is the best way to get to the secondary and tertiary cascades that represent most digestive disorders including IBS. 

IBS is a multifactorial disorder involving environmental factors [food, microbes, infection, smoking] interacting with host factors [ immune system  neural set up and programming at gut, spinal and brain leve]. The neural set up can be either programmed at birth [genetic factors] or after birth [psychological trauma, infection] which lead to a kind of "vigilance arousal" leading to low threshold of pain reception, motor response of the gut, and changes in CNS involving hypothalamico pituitary axis, changes in limbic and prefrontal cortex and overresponse of the enteric nervous system. All these lead to alteration of bowels, passage of mucus in stool [histamine response], pain in abdomen and other parts of body, and altered emotional response which are the key features of IBS.   

This question is very important.

It is out of doubt that  certain pre and probiotics (they are as various as anitbiotics) can  improve the symptoms.

In the other hand, many factors modulate also IBS.

In my opinion, depression is the cause and the other factor only modulators.

I am studying the problem since 30 years.

This neurobiochemical dysregulation (the psychic features beeing consequences and not the cause)  can lead to bacterial changes, as it is associated frequently with changes in the stool's color, testimony af a change in RedOx potential, which is a consequence of bacterial balance.

Moreover, certain forms of constipation are associated with fecal overdigestion, diminishing the stool's volume.

As these symptoms disappear with an efficient treatment of depression , I thinck that  microflora changes are one of the mechanisms of IBS symptoms.

How to recognize depression in gastroenterological practice

Bernard Maroy, 15 January 2009

This article details the conclusions I have reached after analyzing the somatic features of depression over 30 years.

I am a hepatologist who has practiced alcohology since 1979, and aims to understand and treat the main cause of relapsing liver disease. It quickly became clear that depression was a very important component of craving for alcohol. I, therefore, progressively developed algorithms of diagnosis and treatment.

I found that my criteria for depression were validated for several reasons:

Firstly, because they were statistically-associated with classical psychic signs of depression;

Secondly, some had been described previously;

And thirdly, because they disappeared following anti-depressive treatment, relapsing when this was stopped, and disappearing again with further treatment.

The first sign was coccygodynia and pain elicited by rectal touch. I succeed to publish this sign, but as I discovered many further signs it became too long to publish my studies, mainly because publications dealing with depression are rarely accepted. Moreover, it was boring to work hard to publish on out-dated features, when I was far ahead at that moment.

The basis of my work is that depression is a neuro-biochemical syndrome leading to multisystemic dysfuctions and. by no means, a merely psychic disease.

Suspecting depression?

Various digestive signs may be encountered. The most indicative feature is the intermittent appearance of symptoms with fluctuating intensity.

Starting with the mouth - dry or (rarely) excessive salivation, anomaly of taste (mainly abnormal spontaneous taste of any kind). Burning tongue or mouth without any local lesion.

Next the pharynx - globus, sensation of foreign body, frequently on a single side. Characteristic is improvement by or lack of deglutition effect.

Retrosternal pain is typically parasternal, often left-sided. It can realize (improvement after sipping water) a more or less typical reflux syndrome.

Epigastric pain is typically soon after a meal, or non-influenced by it as a heaviness associated with dyspepsia, early satiety, bloating and intestinal noises.

Nausea and vomiting are especially indicative, especially in the morning or when triggered by smell, as is travel sickness in adults. Nauseous reflex can be increased when brushing teeth, swallowing a tablet, during dentistry or upper endoscopy. This dyspepsia worsens with large fatty meals and during purgation for colonoscopy.

The liver can be tender - in part or whole - with a normal consistency, blood tests and ultrasound. It seems to me that depression can be a direct factor of fatty liver.

Depression is an important component of biliary-pancreatic sphincter dyskinesia.

At a colonic level, pain is frequent, usually diurnal, and alleviated by lying down. It is typical if burning or cold, as if owing to the quantitative or qualitative dysfunction of neuronal filters. Mucus can be wet or dry. Diarrhoea is typical if it is irregular, preceded by hard stools, urgent, of a low volume, decreases during the day, and occurs mainly during the morning and after meals, but rarely in the evening.

Constipation is typically propulsive with an empty rectum, even in case of urgency. Stools are rare, frequently small, due to hyperdigestion and difficult to pass, even if soft, owing to insufficient propulsion.

At the anal level, depression can cause various pains, more or less typical, from proctalgia fugax to coccygodynia. Depression is more frequent among fissure patients than among haemorrhoids or abscess patients. Localized pain can be due to peri-anal metameric syndrome, mainly S4.

How to confirm depression when it is suspected?

The first thing to do is to notice if presentation face mobility is normal and whether the hands are wet, then search for allodynia (pain elicited by a normally painless stimulation). Start on spontaneously painful locations, explore successively the different planes: skin (rarely), subcutaneous tissue by pinching or rolling; muscular tensing increases pain and deep planes like bones and insertions.

The search on elective locations: vertex, middle of sternum, xyphoid appendix, extremity of the last ribs, subcutaneous tissue and muscles of abdomen, lateral muscles by pinching, pubis, pubic spines, adductors of thigh, insertions of biceps on tibia and posterior spine joints. These pains can predominate over one or more hemi-dermatomes, frequently bilateral and asymmetric. It can be "all over" and then on the same side on face and body, contrary to organic pains. It seems to be due to an abnormal central treatment of normal afferent pain. Tickling or itching have the same value as pain. The first is a qualitative and the second a quantitative abnormality of central sensation modulation.

Ask the patient these questions:

Do you wake up during night, even for voiding?

Do you fall asleep easily?

Are you tired, especially in the morning?

Do you have difficulty starting the day?

Do you feel sleepy during day, especially after meals or driving?

How is your appetite?

Has your weight changed?

Do you have neuro-vegetative signs: instability, frequent voiding, itching, excessive sweating, spontaneous or evocated by exercise or eating, sexual, memory problems, nightmares?

Are you abnormally nervous, anxious, irritable, pessimistic? If possible, ask the patient's spouse.

Do you have any problem with alcohol?

Once these questions have been asked then decide whether a treatment is warranted. It depends of the perception of impediment by the patient and of his or her vision of the treatment.

This treatment is based on antidepressants adjusted by the "try and failure" method. It is better to start with a relatively low dosage, supra-liminar but infra-optimal (For example, 50 mg of tricyclics reached in a few days).

In the case of poor tolerance, stop the treatment because the medication is not going to be effective. If there is no effect, stop treatment for between 2 and 6 weeks, depending on the urgency of treatment, the number of medications tested and of earlier failures.

Wait until effect is maximal, then increase by steps until effect decreases. Hence, back to earlier dosage. If effect is only fair then begin again. If it is absolutely perfect, continue 6 months at full dosage, then diminish by prudent 2 months steps. Sometimes, a maintenance treatment is necessary.

If the result is good but not perfect, test an association with another antidepressant, preferably of another family, and so on…

Never forget that after stopping a medication its later effect will be frequently less. The curve dose-effect is not linear - flat for subliminar dosage, climbing if efficient and then declining over optimal dosage. These values vary from one patient to another.

Two illnesses can be associated, either because it causes depression or by chance because depression is very frequent all over the world.

Be careful before ascribing a recent pain to depression, even associated with an overlying allodynia.

Finally, the only way to make sure the exclusive responsibility of depression is to cure the patient with an effective treatment.

Further details about signs dealing with digestion and other systems, especially alcoholism, are detailed in English in my website bmaroy.free.fr and in my French language book La Dépression et Son Traitement: Aspects Méconnus. 2005 L’Harmattan, Paris.

Maroy, 04 May 2010

"Open the eyes and you shall see"

Functional diseases, pain and irritable organs are poorly understood, and therefore treated with suboptimal results. In fact, they are studied individually although numerous publications confirm their association with other digestive and extra-digestive dysfunctions. These associations favor a common cause.

Deductive studies, starting with a symptom and trying to understand its mechanism, fail because the mechanisms are complex and also possibly because various mechanisms may cause the same consequences.

I follow an opposite, inductive way. As a hepatologist, I understand quickly that treating the consequences of alcohol was inefficient, unless alcoholism itself and its causes are taken into account. It became clear that depression was the most important mechanism of alcohol craving. I developed therefore, along 25 years, a diagnostic and therapeutic system.

Starting with coccygodynia, it appeared that bodily signs of depression were numerous, frequently evocative and even specific. The association with psychic classical signs, association of signs with each other and the simultaneous disappearance with antidepressants, led me to the following conclusion: depression is a neuro-biochemical syndrome with multi-systemic consequences. The reason this has been overlooked lies in the divergence between neuro-bio-chemical scientific evidence and the day-to-day practice and concepts of dichotomy between soul and body in a platonician point of view. Therefore, depression has been considered more and more as purely psychic, forgetting the concept of endogenous depression and bodily manifestations, formerly well known.

Diagnostic systems used in psychiatry are designed to be specific but fail to define non-depression. As a consequence they are not sensitive. The vast majority of functional digestive troubles appear to me to be the direct consequence of a neurological dysfunction. Cure by antidepressants has confirmed my point of view.

The reason the efficiency of antidepressants is overlooked in many studies lies in the inability to foresee the efficiency and optimal dosage of each medication. So, a given dose of a given molecule improves only part of the patient. If the medication is not tolerated, it is going to be inefficient: change it. Any molecule has a threshold dose (for example, 25 to 50 mg/d for tricyclics), below this dose there is no effect at all (but amitryptiline).

If the medication is efficient, effect increases with dosage until a maximum is reached (a variable from almost nothing to perfect equilibration of depression). In the latter case, carry on a minimum of 6 months before slowly tapering dosage, checking that no sign reoccurs. In the former, change the molecule and try again. Sometimes many medications are efficient; sometimes only one works.

I usually start with a tricyclic, mainly amoxapine 25mg then 50 mg. Tricyclics lead to dry mouth and constipation only when badly tolerated (change molecule) or supra-optimal dosage (taper dosage). I find the following to be the most efficient: clomipramine, imipramine, maprotiline, dosulepine, escitalopram, sertraline, fluvoxamine, and venlafaxine.

An optimal dosage leads frequently to partial effect. If you change the molecule you take the risk of a loss of efficiency if you need to use it again. If you don't change it is impossible to reach a perfect equilibration with this medication and moreover the result is frequently unstable. The logical solution is associating a second molecule to the former. Any risk of association is low in practice, especially if patients are informed and the doctor easy to reach.

I used to associate different classes of drug. The result of this is sometimes inhibition (1+1=0) or no effect at all (1+1=1) requiring change of the new molecule. However, the effect is sometimes additive (1+1=2), requiring the usual dosage of the new molecule, or it can be potentiating (1+1=3), requiring a low initial dosage of the new molecule. In associations I prefer as the second molecule: venlafaxine, mianserine and moclobemide (the latter with special caution).

With the present method, I am able to cure durably more than 90% of digestive functional troubles, together with associated signs: bodily, psychic and relational, as well. It is easy in 70% of cases, a bit difficult in 10%, difficult in a further 10% and problematic in the last 10%. Patients eventually do well as a whole, which is the real task of medicine.

Owing to my private practice, I am unable to perform studies necessary to prove this method. However, importance of results seems worth trying it. Risk of trying does not exist and potential efficiency is revolutionary. Remain taboo!

bmaroy.free.fr

Dear  Geir Bjorklund sir,

  Definately overgrowth of bacteria in the gut has been definitively linked to Irritable Bowel Syndrome in the results of a new Cedars-Sinai study which used cultures from the small intestine, they done test for detection of methane a byproduct of bacteria using BREATH test, so they conclude that the bacteria play a role in developing the IBS.  The antibiotics are used to treat the IBS but the question remains that the what will be the time period of treatment, because the antibiotics may disturbed the normal bacteria flora of gut. in that pre and pro biotics are nowdays use to treat the IBS. taking 10 billion to 100 billion beneficial bacteria per day is recommended for beneficial results. However, further research is needed on individual strains of beneficial bacteria for more refined recommendations.

Gautam Ray,  Christine Ann Edwards, Ierardi Enzo , Bernard Maroy sir for your valuable answers, as I am also doing preclinical research on IBS and IBD, and your answers cleared my some querries regarding the IBS disease.

Thank you

Mithun V. K.  Patil

Department of Pharmacology,

Poona College of Pharmacy,

B.V.D.U.

Pune, India

Alterations of the microbiota are definitely an important contributing factor, and the trigger in altering the microbiota may be the effect of infectious AGE in susceptible individuals. I have posted a questions on this association and provided a recent publication in which I make the argument that pre-biotics have a role to play as an adjunct therapy of oral rehydration solution in reducing the risk of PI-IBS (see attached document).

A large variety of factors are involved in the pathogenesis of IBS (motor dysfunction, dysregulation of brain-gut axis, post-infectious changes, visceral hypersensitinity etc. Altered intestinal microbiota has prompted growing interest in the relationship with human health and diseses. The role of the microbioma in IBS seems to be one of the most important factor involved.

I suggest this recent review :

HL DuPont: "Evidence for the role of gut microbiota in irritable bowel syndrome and its potential influence in therapeutic targets" Aliment Pharmacol Ther 2014; 39: 1033

.  

Vittorio's comment hit a lot of nails on the head. I might add fallen transverse colon, of which we are seeing more and more, primarily in females. When tranverse colons fall from their superior position in the gut they enlarge and increasingly fill with fecal matter, interrupting both water absorption and bile resoption. Both of these interrupted processes contribute to IBS, gall stones, elevated blood lipids, and other concurrent conditions.

I am affraid Max explanations are far from scientifically desmonstrated.

On a métbodological point of view, it's of paramountimmortantnot to confuse causes, consequences and modulating factors.

The most frequent complaints by IBS patients are those of abdominal distension causing abdominal pain or discomfort and bloating,reflecting poor absorption of food ingredients and their subsequent fermentation by an altered intestinal microbiota. However, the question is: what caused the alteration of the microbiota or dysbiosis? The science-based response is AGE in susceptible individuals that leads to post-infectious irritable syndrome.

Bernard, I am not sure whether we would classify fallen transverse colon, something we are seeing more and more, as a contributor or modulating factor. I just wanted to make sure we have this component somewhere in the discussion. Admittedly, in reality IBS is sometimes confused in diagnosis with a number of other conditions, such as colitis and even in some cases Crohn's. 

Max, fallen transverse colon may lead to more difficult colonoscopy but there is no evidence favoring any change in colonic function. If it would, resection would be the solution!

Francisco, bloating is not the consequence of malabsorpsion.

It is important to distinguish subjective and objective bloating. The former is clearly the consequence of an abnormal perception. The latter has mechanical causes.

In my experience, both are of depressive origin.

Bloating as in expand or distend due to gas...  Definitely, there is some subjectivity in relating symptoms and depends on the degree of tolerance, which may vary among patients.  However, the underlining mechanism is a manifestation of food, in this case, not being absorbed and hence fermented by SIBO or alteration in the microbiota with subsequent gas production and distention of intestine or colon. 

An amazing thng happens to our patients who use our exercise machines that help realign their hips and lower spine after treatment or surgery of those areas: they get back their lower abdominal muscle wall, and the fallen transverse colon migrates into its it superior position in the abdomen. When that happens we see (repeatable and predictably) that: hydration improves. blood lipids go down, the constipation/diarrhea cycle canishes, bloating is resolved. So, Bernard, we have no other explanation as to why these marvelous changes occur but see it in every case that is diligent in using the equipment. It is stunning to see over a 8 to 12 week period and undeniable even if no one has yet demonstrated it in a controlled, double blind study. I wouldn't advocate a resection for this when there is another, far less risky solution. But this is our observation, which we can only offer on a case study basis. Of course, egregious dietary changes, such as avoidance of gluten, must accompany some of these cases.

Francisco, excess of gas has never been clearly proved. Slow gas clearance has been blamed as abnormal contraction of diaphragm. Be careful with seemingly obvious explanations.

Max, I never dispute facts. How do you explain variability of bloating, only during the day and according to the hour?

Thank you Bernard, you seem very perceptive.  Giving your understanding of IBS, I would like you  to comment on this manuscript (attached document) that is not based on "seemingly obvious explanations," but rather on reviewing the current scientific literature on alterations of the microbiota (dybiosis) in IBS and a possible measure to reduce its risk. 

Now, Bernard, my mention of fallen transverse colon is merely one sliver of a much larger milieu of issues surrounding IBS and all the other conditions it is confused with. But since you asked the question on bloating, there is hardly any biological abnormality in the human digestive process that is more prone to bloating than an overloaded, substantially expanded transverse colon that is packed with fecal matter that cannot get over to the descending side of the colon. Gas, of course, forming there, and blocking hydration and bile recovery to varying degrees, and being released upon physical movements. Generally, however, we see cycling between constipation and diarrhea  in these cases. But bloating and gas are also in the mix. 

Francisco, thank you for this interesting, indisputable article.

However, dysbiosis could be one of the mechanisms of IBS.

As it is the case for many functional troubles, mechanisms are numerous and very complex, neurological, bacterial, endocrinologic with non-physiological pathways. So, it's, for the moment, impossible to climb from symptoms to causes through mechanisms. As for upriver Nile river, being stopped by swamps in the middle, you must make an induction from the cause to its consequences for IBS and go down the river.

Superb analogy, Bernard! I'll have to remember that one (smile).

Recently one of our paper entitled "Life and Consciousness - The Vedāntic View" has been published in the Journal Communicative & Integrative Biology. An interesting discussion on this paper can be found at: https://groups.google.com/forum/#!topic/online_sadhu_sanga/Mcv2O-yhqLE

From paper:

"The scientific confirmation of the existence of consciousness in unicellular organisms and plants certainly establishes that the brain is not the source of consciousness. Several decades back, research in medical science has also proven that the brain is not the source of consciousness. In 1970, Robert White and his team successfully transferred the head of a rhesus monkey to the headless body of another monkey. The monkey survived for 8 days.68 Researchers are also attempting to perform the same scenario with human beings.69 It is reported that if a human head has been detached under controlled conditions, it must be reconnected to the circulatory flow of other person's body (which is conscious or living) within one hour.70 Therefore, brain-based analysis for understanding consciousness (neuronal analysis) does not have very bright prospects."

Paper: Life and Consciousness - The Vedāntic View

DOI: http://dx.doi.org/10.1080/19420889.2015.1085138

Journal: Communicative & Integrative Biology

Publication date - 09 Oct 2015

Author: Bhakti Niskama Shanta - http://orcid.org/0000-0002-2039-3249

Bacterial infections of the intestines become an issue when individuals are taking long-term GERD medicines, which disengages the acid barrier of the human digestion system. Such medicines allow unfavorable bacteria that otherwise would be destroyed in the stomach acids to make it into the bacterialogically friendly environment of duodenum and upper intestine.

It's perfectly true. However, this barrier is only partial, as it has been studied with Salmonella sp.

Moreover, microbiote is remarkably stable over time in a given individual and it's efficiency against colonization by pathogens more important than that of acid.

Bernard brings out the point of partiality and somewhat selectivity of the human stomach acid barrier. But that would be true for all the other barriers to bacteria entering the body. For a review of those barriers:

http://www.bbc.co.uk/schools/gcsebitesize/science/21c_pre_2011/disease/diseaseresistancerev_print.shtml 

Moreover, the acid barrier is a phenomena that must not be disturbed if an individual wants to be healthy: 

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134116

But, most importantly, we are looking at far more than salmonella being killed by the acid barrier. E coli, which is increasingly prevalent in the US food supply, is also controlled by humans due to the acids in the stomach and their effectiveness in killing the dreaded bacteria before they bring lethal disease:   

http://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.46611-0?crawler=true&mimetype=application/pdf

My earlier contention was that overuse of GERD (acid reflux) meds are dangerous to human health, that many problems occur, not the least of which is the dismissal of the acid barrier, when physicians over-prescribe these medicines. We find this an alarming trend in US medicine, and feel there are far better ways in tackling acid reflux than simply following the pharmaceutical recommendation. For some background and review I am attaching one of my older monographs.

Thank you. 

Many persons have low acid spontaneously, like after gastric surgery or linked to gastric atrophy, whatever its cause. It remains to be demonstrated in vivo that this is harmful.

Moreover, most of foreign species just go trough and very few become established.

The difficulty to modify microbiote, especially durably, with pro or prebiotics is in keeping.

However, it's out of question that commensal flora is of paramount importance in some illnesses and, probably, maintaining health.

The problem is how to change it.

 You are correct in short term cases and where the US food supply is not the problem extant. But the cases we see today come in having taken GERD meds (prilosec, etc.) for years at a time--even 10-12 years. My contribution addressed the question if harmful bacteria like salmonella and e Coli, which pervade the US food supply today, can bring on symptoms consistent with IBS. And my answer is yes, it can, in addition to many other egregious health effects such as bone loss, nutrient deficiencies, and neuropathies. Of course, we are speaking of a population (US, where we represent less than 4% of the world's population) taking the vast majority of prescription medications of this type. 

As I have said in my previous reply that IBS is too complex a condition to pin point a single factor (intestinal bacteria) as the cause. As Dr. Enzo says "each paper is a small piece to build a large mosaic", the contribution of intestinal bacterias may be by inducing low grade inflammation in intestine, alteration in overall microbiome of the gut of an individual, induction of symptoms in post infectious IBS  and even affecting the psyche of an individual. 

I agree with you Gautham. IBS is more a syndrome than an illness and it's very difficult to understand causes through study of mechanisms. Moreover, differentiating modulating factors of causal is very difficult. For instance, you suggest that psychic troubles could be the consequence of dysbiosis and, in my experience, it's the reverse, treatment of depression changing intestinal dysbiosis.

Everibody agree that IBS is a syndrome (Irritable Bowel Syndrome). The alteration of intestinal microbiota is a foundamental step in the onset of mucosal inflammation and increasing the intestinal epithelial permeability and barrier disfunction, allows toxic metabolites trasmigration into the bloodstream  and in the central nervous system

Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013; 155: 1451–63.

Vittorio. I admire your certainty. I hope this hypothesis is going to solve the problem. However, I am not sure that the problem is totally solved, if only because changing the microbiote is so difficult.

Dear Bernard, obviously it is no a certainty and the problem is not solved but not so rare evidencies support this hypotesis. Moreover I think that change the microbiota is not so difficult: for example in pts with refractory  Clostridium difficile infection fecal transplant can lead to a dramatic conseguence with a haeling rate of 90% of cases (van Nood E, Vrieze A, Nieuwdorp M, et al. N Engl J Med 2013; 368: 407–15).

You are right Bernard. Giving probiotics helps some patients of IBS but not others.

Dear Vittorio. This is perfectly exact. However, to the best of my knowledge, this transplantation has not been tested among other illnesses like IBS and IBD.

The responsibility of Cd for pseudomembranous colitis is out of doubt. The lack of dominant sp. play an important role in repression of Cd. Implantation of deficient sp. or changing durably the proportion of various bacteria may be more difficult. If possible, it would be a major tool for determining the responsibility of abnormal microbiote in the illnesses.

I don't regard IBS as a diagnosis. It is the acceptance that there are digestive problems, that have not so far been diagnosed.

It may be caused by over-consumption of fructose, some of which cannot be absorbed, and the resulting supply of fructose to gut bacteria.

It may be due to selective killing of beneficial bacteria by antibiotics. Probiotics can help, but quality matters.

It may be caused by a chronic infection.

Acute doses of boron cause acute digestive symptoms, and I suggest that a chronic intake of boron from diet or supplements can cause chronic symptoms.

Lectins, for example in bran and wholemeal bread, can cause symptoms.

Poor sulphate production can lead to poorly sulphated glycosaminoglycans, increasing gut permeability.

There may be a lack of short chain fatty acids from diet or made by gut bacteria.

The diet may be deficient in omega 3 fats, molybdenum, or vitamins B2, B5 and B6, all of which are involved in making sulphate..

Taking factors like these into consideration, I find IBS can usually be quickly resolved.

Margaret provided a solid and comprehensive review of the causes of IBS and other syndromes that are too often interpreted as diseases instead of the symptomatic subsets they are. Dietary factors obviously are in the forefront of such symptoms and must be addressed before any other approach is even remotely feasible. 

Dr.McRoy, I was actually trying to point out the  strong association between mental depression and IBS and intestinal microbiota which is believed to be involved with IBS also has significant association with the mind set. Please refer to following

[1] Gut Microbiota and Brain Function: An Evolving Field in Neuroscience. Foster JA, Lyte M, Meyer E, Cryan JF.Int J Neuropsychopharmacol. 2015 Oct 4. pii: pyv114. doi: 10.1093/ijnp/pyv114.

[2]The Microbiome in Mental Health: Potential Contribution of Gut Microbiota in Disease and Pharmacotherapy Management.Flowers SA, Ellingrod VL.Pharmacotherapy. 2015 Oct;35(10):910-6. doi: 10.1002/phar.1640

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I accept all that is said about diet. But we in our recent experience have seen so many convincing causes of duodenal ulceration. Earlier generations probably postulated many causes of TB. Both now known to be bacterial in origin. My firm belief is that the cause of IBS is a yet unidentified bacteria. And that the other putative causes provide the necessary environ for that bacteria.

Obviously, there are some undiscovered bacteria involved in many cases, and part of the problem with identification of the culprit would be in its uniqueness to the individual's body chemistry and metabolism. But the underlying issue of differences in immunology appear to go to the more fundamental question of why some and not others?  

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Per above notes from esteemed colleagues, it is appropriate that it designated a syndrome and not a disease; accordingly, diagnosis is by default and there are various factors involved, i.e., dysbiosis, diet-related intolerance and the patient's tolerance to gastric pain culturally based and mental status.  It is quite possible that there is no one-single cause of it.  Also, there seems to be a precipitating event as well.  People are fine and they get an infectious diarrhea and 20-30% of them develop IBS within 6 mo of the diarrheal episode.  Are those who develop IBS post diarrheal infection, genetically predisposed?

We found that people with IBS had a high cysteine to sulphate ratio, which means they were not efficient at making sulphate. This suggests that there is an inherited susceptibility. We found an abnormal ratio in family members, but they did not necessarily develop the same condition as each other. For example, we found a high ratio in

an Asperger son and in his multiply chemically  sensitive mother

 a daughter with rheumatoid arthritis and in her depressed mother

a daughter with endometriosis and in her mother with rheumatoid arthritis

a hyperactive daughter and in her mother with IBS

a man with IBS and in his sister with migraine

a mother with leukopenia and in her a son with anaemia.

Others with a high ratio had close relatives with motor neurone disease, severe learning difficulties, hyperactivity, fragile X autism, psoriatic arthritis, multiple chemical sensitivity, multiple food sensitivity, multiple sclerosis, rheumatoid arthritis and leukaemia. We were not able to test the ratios of these relatives, but most of these conditions have been related to poor sulphate conjugation.

The maximum ratio of cysteine x 1000 to sulphate in healthy volunteers was 121, apart from one who was healthy at the time but had recurrent IBS, and one who developed MS 15 months later. However the average ratio for those with IBS was 1589.

A Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome.

Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG.

Yes! Please take a look at the following RG links.

Article The gut microbiome and irritable bowel syndrome

Article Small Intestinal Bacterial Overgrowth and Irritable Bowel Sy...

Article Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota ...