Discussion
diarrhea, cramps, constipation, hypoglycemia, abdominal distension, T2DM
HYPOGLYCEMIA, INSULIN RESISTANCE, DISEASES, SIDE EFFECTS
This study aimed to evaluate the improvements of T2DM patients and their gut microbiota by FMT alone and FMT plus metformin, compared with metformin. Results showed that FMT alone and FMT plus metformin significantly improved insulin resistance (HOMA-IR), HOMA-HBCI, BMI, FBG, and PBG within 4 weeks after intervention, and modified gut microbial communities by colonization of donor-derived microbiota. Correlation analysis revealed that Metformin is currently widely used as the first-line drug for the treatment of T2DM patients, as recommended by clinical guidelines, due to the improved glycemic profile and reduction in cardiovascular mortality without the risk of hypoglycemia and/or body weight gains (The patients included in our cohort were diagnosed with T2DM and were not receiving prior regular drug treatment or dietary intervention. These T2DM patients had poorly controlled blood glucose or serious insulin resistance and received no other medications for the treatment of other diseases. During the observation period, the enrolled patients did not perform any physical exercise other than daily life activities and received generally consistent dietary regulation. This design enabled us to diminish the effects of major confounding factors that have a known impact on the gut microbiome. Clinically, not all T2DM patients benefit from the use of metformin or respond to metformin quickly. For example, some patients exhibit strong insulin resistance and weak insulin secretion function despite metformin treatment. Therefore, FMT was used to assist metformin treatment in these patients to quickly improve their sensitivity to metformin.The present study demonstrated that, although metformin could improve the blood glucose, the addition of FMT promoted the improvement further. Many studies have shown that gut microbiota are closely related to glucose metabolism (A decent engraftment of donor-associated microbiota taxa in recipients during the FMT procedure is one of the prerequisites that guarantees the efficacy of FMT. It is generally believed that the diversity of gut microbiota is closely related to gut health, and the colonization rate of donor flora in the recipient is an important indicator to evaluate the success rate of transplantation. In our study, about 2/3 of the FMT group and the FMT plus metformin group reached the target of ≥ 20% donor derived microbial species, which was significantly increased by 23 compared with other previous studies (Side effects of FMT include mild and self-limiting abdominal discomfort, cramps, abdominal distension, diarrhea or constipation, and very few diseases that cannot pass screening tests (Our study has several limitations. First, the relatively small sample size was not sufficient to evaluate the subtle differences or mechanisms associated with metformin treatment with or without FMT therapies. Second, the study period was limited to 4 weeks, restricting our understanding of the relationship between long-term clinical efficacy and engraftment of donor-associated microbiota. Third, due to scarcity of the donors, we used multi-donor FMT at different FMT times to enhance the microbial diversity transferred to recipients. However, a fixed donor choice based on donor-recipients matching for patients would help eliminate any confounding factors.