Research into the human microbiome is in full swing. In addition to its thorough pathophysiological understanding, the focus is also on therapeutic applications.
At present, there is a flourishing interest and research on the human microbiome, with many laboratory and clinical studies taking place on this fascinating component of our “holobiontic” existence. In a recent paper1 published in Cell Host & Microbe (Impact Factor 2018: 15.8) it was reported that changes in the composition of the intestinal flora in type 2 diabetes are mainly related to obesity and the intake of dietary supplements and medications, and less than previously assumed, on diabetes itself.
The research is led by the Institute for Clinical Molecular Biology of the Medical Faculty (German acronym: IKMB) at Christian Albrechts University (CAU) in Kiel, Germany. It is done in cooperation with colleagues from Germany, the USA, and Norway.
The scientists analyzed the intestinal microbiomes of obese patients with type 2 diabetes and of slim and obese non-diabetics (n = 153, 633 and 494 respectively). The stool samples were taken from cohort studies on metabolic diseases. The results are summarized as follows:
The researchers are now looking for further funding for an independent research project in order "to search specifically for therapeutic starting points for metabolic diseases in the microbiome". “The microbiome is particularly interesting because it is much easier for us to influence than, for example, our own genome”, the researchers have explained.
This procedure is already being used, and there appears to be something to it. In the case of recurrent Clostridium difficile infections (CDI), this procedure is now being used routinely and with great success. In a randomized Canadian study, the success rate after a single treatment was over 96%. The significantly simpler and more comfortable capsule application for patients proved to be not inferior to colonoscopy.2
Otherwise, the data on cure rates of > 90% were mainly obtained from observational studies. In a current meta-analysis with 13 included studies, the average success rate in randomized studies was significantly lower at almost 70%. The application of the donor microbiome via enema did not perform as well as colonoscopy or orally.3 Of importance for fecal microbiota transplantation (FTM) is donor screening for multi-drug resistant organisms, as the FDA reported of a clinical study case with one death after an FTM.
There is a lot of research into possible applications for FMT in other diseases, but the evidence to date for metabolic diseases such as diabetes is still very limited. After all, it has already been shown that stool transfer from slim donors significantly improves insulin sensitivity in obese patients with metabolic syndrome.4
New Zealand scientists have identified some characteristics of "super donors", that is, those stool donors whose fecal matter has provided the most successful transplants. The existence of such “super donors” has long been suspected. Scientists determined that a high bacterial diversity and the presence of butyrate are amongst key “super donor” stool characteristics. In the particular case of butyrate (also known as butanoate), it is produced by specific intestinal bacteria and plays a role in the regulation of immune defense and energy metabolism. A lack of butyrate is associated with obesity and type 2 diabetes.
In fact, the use of stool transplants to treat various diseases is not a modern invention. Rather, this therapeutic trick has a 1,000-year history originating in China.5 A recent case report6 on the use of FMT in a 46-year-old woman with diabetic neuropathy comes from China, the first of its kind according to the authors.
The patient, who has been suffering from diabetes and high blood pressure for 8 years, was admitted to the hospital because of sensitive pain on her right thigh and poor blood sugar control. The usual antidiabetic and analgesic therapeutic options could not manage the symptoms. After two FMTs, glycaemic control improved within 3 months. The pain caused by diabetic neuropathy was remarkably alleviated without any noticeable side effects during treatment and follow-up.
References:
1. Thingholm et al Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition. Cell Host Microbe. 2019;26(2):252-64.e10. doi:10.1016/j.chom.2019.07.004
2. Kao D et al. Effect of Oral Capsule- vs. Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA 2017;318(20):1985-93. doi: 10.1001/jama.2017.17077
3. Tariq R et al. Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis. Clin Infect Dis 2019;68(8):1351-8. doi: 10.1093/cid/ciy721
4. Aron-Wisnewsky J et al. Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes? Curr Diab Rep 2019;19(8):51. doi:10.1007/s11892-019-1180-z
5. Schlehe JS, Ussar S. The microbiome: influence on obesity and diabetes. Dtsch Arztebl 2016;113(17):[27]. doi:10.3238/PersDia.2016.04.29.08
6. Cai T et al. Fecal microbiota transplantation relieves painful diabetic neuropathy. A case report. Medicine (Baltimore) 2018;9(50):e13543. doi:10.1097/MD.00000000000135