The literature shows that gut microbiota plays a significant role in the development and progression of liver diseases. Research suggests that a disturbance to the gut microbiome leads to hepatic steatosis, liver inflammation, hepatic encephalopathy and fibrosis. There are several papers that indicate that gut microbiota is important to the induction of NAFLD. Faecal gut microbiota transplantation (FMT) is used to restore gut microbiota homeostasis as a treatment for various chronic diseases such as diabetes and Alzheimer’s disease. The composition of the FMT is critical to the liver-brain interaction and important to amyloid beta homeostasis and the reversal of diabetes and Alzheimer’s disease. FMT and the improvement in liver function is critical to the success of FMT in the treatment of diabetes and Alzheimer’s disease.
RELEVANT REFERENCES:
1. Kim KO, Gluck M. Fecal Microbiota Transplantation: An Update on Clinical Practice. Clin Endosc. 2019 Mar;52(2):137-143.
2. Xiang W, Xiang H, Wang J, Jiang Y, Pan C, Ji B and Zhang A (2023) Fecal microbiota
transplantation: a novel strategy for treating Alzheimer’s disease. Front. Microbiol. 14:1281233.
3. Sharma, A and IJ Martins. The role of Microbiota in the pathogenesis of Alzheimer’s disease. Acta Scientific Nutritional Health. 7.7 (2023): 108-118.
4. Manzoor, R. Ahmed,W. Afify, N. Memon, M. Yasin, M. Memon, H. Rustom, M. Al Akeel, M. Alhajri, N. Trust Your Gut: The Association of Gut Microbiota and Liver Disease. Microorganisms 2022, 10, 1045.
5. Jasirwan COM, Lesmana CRA, Hasan I, Sulaiman AS, Gani RA. The role of gut microbiota in non-alcoholic fatty liver disease: pathways of mechanisms. Biosci Microbiota Food Health. 2019;38(3):81-88.
6. Hrncir T, Hrncirova L, Kverka M, Hromadka R, Machova V, Trckova E, Kostovcikova K, Kralickova P, Krejsek J, Tlaskalova-Hogenova H. Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions. Microorganisms. 2021 Apr 29;9(5):957.
7. Gupta S, Allen-Vercoe E, Petrof EO. Fecal microbiota transplantation: in perspective. Therap Adv Gastroenterol. 2016 Mar;9(2):229-39.
8. Appetite Regulation and the Peripheral Sink Amyloid beta Clearance Pathway in Diabetes and Alzheimer’s Disease. Top 10 Commentaries in Alzheimer’s Disease (e-book). 2019;2:1-11. www.avidscience.com
Thanks for the interesting question which motivated me to read some valuable work you cited. I have a few comments and I hope someone corrects me if I'm wrong or have misunderstood the statements:
- Characterizing FMT's composition as "critical" to amyloid-beta, diabetes reversal, etc. may be an overstatement based on current evidence. The pathways likely involve multifaceted effects beyond just the transplanted microbiota.
- Saying improved liver function is "critical" for FMT's success in Alzheimer's/diabetes also seems an overstatement. The statement implies a causative relationship between improved liver function and the success of FMT in treating diabetes and Alzheimer's disease. However, the provided papers do not establish such a direct causal link. Other mechanisms like gut-brain axis modulation, modulation of neuroinflammation and amyloid-beta clearance can make the interplay between the gut microbiota, liver function, and the pathogenesis of specified conditions highly complex and difficult to interpret.
From my understanding of your provided references and current literature, I think some of the statements and conclusion made in this post appear to be a bit of stretch and lack enough evidence.
Faecal microbiota transplantation (FMT) is a treatment that involves transplanting gut microbiota from a healthy donor to a recipient to restore the recipient's gut flora. This therapy has been explored for various conditions, including Clostridium difficile infection, inflammatory bowel diseases, and metabolic disorders. However, its effects on liver diseases, diabetes, and Alzheimer's disease are areas of ongoing research.
FMT and Liver Diseases
There is growing evidence that FMT may influence liver diseases, particularly non-alcoholic fatty liver disease (NAFLD) and liver cirrhosis. Dysbiosis, or imbalance in the gut microbiota, has been linked to liver disease progression through the gut-liver axis. FMT can potentially modify this axis by restoring a healthy microbiome, which might reduce liver inflammation and fibrosis.
- NAFLD and Liver Cirrhosis: Studies have shown that FMT can improve liver function and reduce inflammation in patients with NAFLD and cirrhosis. A study by Bajaj et al. (2017) indicated that FMT improved cognitive function and reduced endotoxemia in patients with cirrhosis and hepatic encephalopathy.
- Safety Concerns: While FMT shows promise, there are concerns about the safety and long-term effects of this treatment, especially in immunocompromised patients, as there have been reports of serious infections following FMT.
FMT and Diabetes
The gut microbiota plays a crucial role in metabolic processes, and dysbiosis has been linked to type 2 diabetes (T2D).
- Insulin Sensitivity: FMT has been shown to improve insulin sensitivity in patients with metabolic syndrome. A study by Vrieze et al. (2012) demonstrated that transferring microbiota from lean donors to individuals with metabolic syndrome improved insulin sensitivity.
- Glycemic Control: Other studies have suggested that FMT can help in better glycemic control, though results are mixed, and further research is needed to establish consistent benefits.
FMT and Alzheimer’s Disease
The gut-brain axis suggests a connection between gut microbiota and neurological conditions, including Alzheimer's disease (AD).
- Cognitive Function: There is emerging evidence that gut microbiota may influence cognitive function and neuroinflammation, which are key factors in AD. Some animal studies have shown that FMT can modulate brain function and reduce amyloid plaques, which are characteristic of AD.
- Human Studies: Human studies are still in early stages, but preliminary results suggest potential benefits of FMT in modulating gut microbiota to improve cognitive function and reduce neuroinflammation in patients with AD.
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