Most scholars would agree that viruses, particularly enteroviruses, play a key role in triggering autoimmune diseases like type 1 diabetes. Yet their identities and exact roles remain speculative.
What i am wondering is whether it is plausible that the 'hit and run' viral attack is against bacteria in the gut, not the actual host.
A bacteriophage could pathologically alter the microbiota of the host (destroying protective strains/ allowing for novel 'bad' ones to develop) causing a loss of self-tolerance for the immune system that leads to beta cell destruction.
Because the effects of the virus are mediated through the microbiota and the virus never actaully enters the bloodstream or tissue, there would be no trace of it left for scientists to retrospectively identify after T1D onset.
In addition, a virus that weakened the microbiome could not only damage immune tolerance, it could leave the host more vulnerable to other viruses as the G.I tract defences are compromised.
So a newly diagnosed type 1 diabetes patient may have a recent history of viral infections, coxsackie viruses etc, which are investigated as triggers for beta cell destruction, but in fact would just be a side effect of a damaged microbiome.
I would also like to know the answer of this question. However, I don't think there is any literature available for it.
What a brilliant question! I wish I could help more in this matter, but apart from agreeing with what you are saying, I can only suggest that more research is required. My interest in this issue lies with my wife, a type 1 diabetic for 38 years, who regards it as just "one of those things". Your question gives me hope that the real reason for her illness may one day be explained, thank you.
I also think this is a very interesting question and certainly given the info that is beginning to flow from study of the gut microbiota, the question is extremely apt. There remains the burning question, why does one person with HLA-DR3/DR4 onset with diabetes at age 5 but another onsets at age 25, and yet another at age 45? What are the differences. While I wholeheartedly endorse exploring the above question, I will put out there that type 1 diabetes MAY have several different disease forms. While aberrant microbiota, or a bacteriophage affecting gut flora COULD be causal in some individuals, something else was responsible in others. It is more complicated than we think even now.
yes! It is complete complex metabolic disorder. Really surprising to continue for T1D for pretty 38 years. This must be pancreatic cells deficiency may be lesser mass of B cells. S N Mishra
If it were true, Diabetes should seem to be a contagious disease. Epidemiology should have picked it up a long time ago along with genetic influences. Those in close proximity would be more likely to get diabetes.
Richard has a good point. We may have evidence of this in that a predisposition to diabetes is passed from mother to offspring not father to offspring, as are the gut flora.
Why do we assume viruses? All that is needed is something that makes the cell look odd to the immune system. Since I have cured my type 2 diabetes with all the complications by eradicating a C. novyi type A infection, I have been wondering if the alpha-toxin of this organism could also trigger type 1 diabetes. The alpha-toxin affects all the hexamine signalling pathways and damages the actin cytoskeleton so it could make beta-cells look foreign to the immune system. C. novyi's evolutionary imperative is to create a high glucose environment in the host, so any trait enhancing serum glucose would be selected for. The alpha-toxin is a very large molecule so could contain more than one active site. It should be possible to look for genetic differences in C. novyi isolated from the guts of type 1 and type 2 diabetics.
There is paternal transmission of diabetes risk as well. But it is lower for type 2 diabetes.
"""In conclusion, our findings revealed that in the offspring of type 1 diabetic patients, the increase in the recurrence risk of type 1 diabetes was not more rapid compared with that in the background population. In the multivariate analyses, statistically significant predictors of type 1 diabetes in the offspring were male sex of the diabetic parent, young age at diagnosis in the male parent, and the more recent year of birth of the offspring."""
""Our study confirmed the repeatedly shown phenomenon that men with type 1 diabetes are more likely to transmit diabetes to their offspring than women with type 1 diabetes.""
http://diabetes.diabetesjournals.org/content/55/5/1517.full
Richard,
I would challenge your comment, primarily because there are so many leading T1D specialists that consider viruses play a role... i will hide behind them...
The virus neednt be contagious.
Epidemiologically, prevalence is rising profoundly in urban, developed countries where people are in close contact. it does not prove a viral trigger but it does not disprove it either. There is some variable (or variables) compounding genetic susceptibility.
The role of the gut as a regulator of type 1 diabetes was suggested in animal studies, in which changes affecting the gut immune system modulated the incidence of diabetes.
Alterations in the intestinal microbiota and exposure to enteric pathogens, regulate the development of autoimmune diabetes in animal models. It has been demonstrated that these modulations affect the gut barrier mechanisms and intestinal immunity. Because the pancreas and the gut belong to the same intestinal immune system, the link between autoimmune diabetes and the gut is not unexpected. The gut hypothesis in the development of type 1 diabetes is also supported by the observations made in human type 1 diabetes.
Ref:-
Is the origin of type 1 diabetes in the gut?
Outi Vaarala
http://www.nature.com/icb/journal/v90/n3/full/icb2011115a.html
In case anyone in the list attending world internal medicine congress at chili this year on mid november, we may even talk about viral hypothesis over there. Juliie tdefinetely points out an important issue that more collaboration and updated ideas are needed so as to better focus on the viral hypothesis. yes, mumps ,is another issue but if this is true not all mummps history or lack of history not linked to T1DM. may that be because it is not only mummps virus but evemn that virus if not processed by the bacteria beta cell desteruction des not happen. Interesting... keep going !
It cant be a bacteriophage because most of the times its not the recent infection & its insult to the immune system because of Ag - Ab reaction which damages B cells of pancreas.
P. B. Tirupathi Pichiah's comment on gut barrier mechanisms fits nicely with my C. novyi hypothesis. One of the principle actions of the alpha-toxin is to produce perforations in membranes. (Pharmacological and Biochemical Studies of Cytotoxicity of Clostridium novyi Type A Alpha-Toxin PETER BETTE, JURGEN FREVERT, FRANK MAULER, NORBERT SUTTORP, AND ERNST HABERMANNL) This explains kidney problems, retinal bleeding, and lower limb oedema. It may also explain the link between L-dopa respondent Parkinson's and type 2 diabetes. The pattern of the development of Parkinson's lesions is consistent with some organism perforating the gut and swimming up the vagus nerve and progressively infecting the brain stem. Molecular modelling shows that L-dopa and the polarised form of N-acetylglucoseamine (the alpha toxin substrate) would both fit the same site having a triangle of hydroxyl group receptors. Anything reacting with the negatively charged oxygen on the N-acetylglucoseamine would change the hybridisation state of the nitrogen atom and provide an ejection mechanism. L-dopa has no such mechanism so may bind irreversibly reducing the L-dopa and hence dopamine levels. This would also explain why the sub-mucosal layer of the duodenum suffers extreme oedema on injection with the toxin while the same tissue in the stomach is unaffected. The stomach has plenty of L-dopa to facilitate dopamine signalling. Diabetic neuropathy may be the result of lack of dopamine mediated signals from the motor cortex. My neuropathy has cleared up and fine motor control in all limbs has normalised as I have eliminated the spore load of my pet Clostridium. Telling the world is proving problematical since the concept of a cure is banned on most diabetes forums.
Juliet Preston refers to the epidemiological evidence. One of the main factors in the change to a western style diet is the inclusion of large quantities of factory-farmed meat. Check out the veterinary literature. The cost of C. novyi in terms of lost feed conversion is less than the cost of vaccination. Infected animals enter the human food chain. I have seen pig's liver in my local supermarket with the lesions of necrotic hepatitis known as aero-chocolate liver. This must be loaded with C. novyi spores which are not inactivated by cooking.
The most comprehensive literature review on this organism is still my Google Knol, “Does the diabetes epidemic have a bacterial cause?” I will be adding the L-dopa data and hosting it on my web site in the near future. Three years ago I was an uncontrolled diabetic with all the complications. This summer when sea kayaking I did 5 miles in 40 minutes. It hurt like hell for the next two days but going from terminally ill to this level of athletic performance at the age of 63 was achieved by measures to combat C. novyi without any diabetic medication.
Autoimmunity (inadequate) is more probable in immature lymphocytes (immunity is immature in infancy). Immature immune response against a "bacterium" (altered or pathogenic), may resemble a "cellular" type immune response. (cytokines, CD4, CD8, IL2, IFN-gamma, IL4, 5, 6, 10). And this immature immune response, can be autoimmune too (as in beta cell, etc.)
I think that the origin can be different viruses and different bacteriophages, and depends of the kind of gut microbiota and of the maturity of the immune system (or quality of the immune system).
Gut microbiota can be fermenter or putrefactive. The fermenter microbiota stimulate immunity.
It is certainly a stimulating question, unfortunately no much research in the area has been done. Bacteria-activacted gut- lymphocytes can surely migrate to pancreatic lymphonodes and may attack beta cells by a molecular mimicry mechanism. Your hypothesis may support our findings regarding the presence of the pathogen Mycobacterium paratuberculosis (MAP) in the gut of T1D patients. MAP antigens homologous to beta cells antigens (e.g. ZnT8) are responsible for triggering the disease
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