Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients

Abstract

BackgroundIncreasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.MethodsWe enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.ResultsWe found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family Rikenellaceae and the genus Anaerotruncus (family Ruminococcaceae) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.ConclusionOur findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of Rikenellaceae and Anaerotruncus in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.

Pharmacomicrobiomics and type 2 diabetes mellitus: A novel perspective towards possible treatment

“…In addition, FMT, a process of transferring stool from a healthy donor or antidiabetes treatment subjects to mice, displayed a significant improvement in microbial composition and metabolic homeostasis ( 131 ). A prospective study revealed that FMT could bring benefits for the management of T2DM via modulating levels of certain microbiome such as Rikenellaceae and Anaerotruncus ( 132 ).…”

Effects of Oral Glucose-Lowering Agents on Gut Microbiota and Microbial Metabolites

“…Thirdly, FMT from normal glucose tolerance or antidiabetes treatment subjects to mice revealed a significant improvement in gut microbiota composition, glucose homeostasis, and metabolic health (17,124,172). Despite that this promising treatment was still in its infancy (173)(174)(175), FMT combined with antidiabetes drugs might bring novel interventions and perspectives in T2DM management. The effects and mechanisms underneath these potential treatment schedules are still unclear, and it is vital to further develop meaningful and applicable interventions combined with intestinal microbiota in the future study.…”

Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols

“…Most studies assessing the efficacy of FMT are conducted in animal models, with fewer studies in patients with T2DM. For example, a recent study evaluating clinical responses to FMT of 17 human participants, showed that 11 of them (64%) had statistically significant decrease in hemoglobin A1c (HbA1c) and blood glucose, while post-prandial C-peptide, a measure correlated with serum insulin, was elevated ( 46 ). Microbiota analysis revealed increases of the genus Anaerotruncu s, which has been associated with increased insulin resistance ( 47 ).…”

“…Microbiota analysis revealed increases of the genus Anaerotruncu s, which has been associated with increased insulin resistance ( 47 ). The individuals harboring increased abundance of Anaerotruncu s exhibited a better clinical response to FMT intervention ( 46 ), indicating that this bacterial genus may be a marker of treatment efficacy in diabetics. Results from another recently conducted study indicated that FMT-induced gut microbiota changes were correlated with improvements in blood glucose in T2DM ( 48 ).…”

“…Preferred delivery methods amongst different diseases were mostly similar, however, varied amongst different diseases. For example, in metabolic diseases, GvHD, CD and depression, FMT was administered through endoscopic approaches or oral capsules ( 20 , 46 , 69 , 101 , 132 , 135 ), while studies evaluating UC and IBS preferred colonoscopy or rectal enema as the distal colon is the most affected ( 92 , 94 , 95 , 104 , 106 ). The efficacy, advantages and disadvantages of the various delivery methods are further discussed in the following sections.…”