Safety and efficacy of adjuvant fecal microbiota transplantation therapy in patients with diabetes mellitus: A systematic review and meta-analysis

Abstract

Objective

Exploring the Safety and Efficacy of Fecal Microbiota Transplantation in Treating Diabetes Mellitus

Methods

A systematic search was conducted across four databases (PubMed, Cochrane Library, Web of Science, and Embase) for relevant studies published up to March 2025. The primary outcomes of interest included glycemic parameters, such as glycated hemoglobin (HbA1c), fasting blood glucose (FBG), Postprandial 2-Hour Blood Glucose (2H-PBG), fasting C-peptide (FCP), and postprandial 2-Hour C-peptide (2H-FCP). Secondary outcomes included lipid profiles, blood pressure, and uric acid levels. Heterogeneity was assessed using Cochran’s Q test and the I² statistic. A fixed-effects model was employed when no significant heterogeneity was observed (I² < 50 % or P ≥ 0.10 for the Q test); otherwise, a random-effects model was applied. For outcomes reported in consistent units, weighted mean difference (WMD) were calculated, while standardized mean difference (SMD) were used for outcomes measured in different units. Subgroup analyses were performed to assess the effects of fecal microbiota transplantation (FMT) on different types of diabetes mellitus and various intervention protocols. Meta-regression was conducted to explore potential factors influencing the effects of FMT on glucose metabolism. Publication bias was evaluated using Begg’s and Egger’s tests, with P < 0.05 indicating potential bias. The quality of evidence for all outcomes was assessed using the GRADE framework.

Results

This meta-analysis included 6 studies to investigate the effects of adjunctive FMT on glycemic and metabolic parameters in patients receiving conventional treatment. The results demonstrated that FMT supplementation significantly reduced 2H-PBG [SMD −2.74, 95 % CI: −3.78 to −0.63], TG [WMD −0.32, 95 % CI: −0.57 to −0.08], and ALT [WMD −2.67, 95 % CI: −4.56 to −0.78]. Subgroup analysis by diabetes type revealed that FMT exhibited a favorable trend in lowering 2H-PBG in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. Notably, FMT significantly decreased FCP and 2H-FCP in T1D patients but increased these parameters in T2D patients. Additionally, FMT was found to reduce homeostasis model assessment of β-cell function (HOMA-β) in T2D patients, while showing no significant impact on T1D patients. Subgroup analysis by intervention modality indicated that both oral capsule administration and feeding tube delivery exhibited trends toward reducing 2H-FCP. Meta-regression identified that patients with lower baseline levels of TC and LDL derived greater glycemic benefits from FMT. No significant adverse events were reported across all included studies. Evidence quality assessment classified DBP, TC, TG, LDL, and uric acid as low-quality evidence; weight, BMI, HbA1c, FBG, 2H-PBG, FCP, 2H-FCP, HOMA-β, SBP, HDL, alanine aminotransferase(ALT), aspartate aminotransferase (AST), and creatinine as moderate-quality evidence, and Homeostasis Model Assessment of Insulin Resistance(HOMA-IR) as high-quality evidence.

Conclusion

When combined with conventional treatment regimens, adjunctive FMT may provide additional improvements in postprandial blood glucose and TC in patients. Notably, FMT may offer more pronounced advantages in glycemic parameters for individuals with lower baseline levels of TC and LDL. However, the safety profile of FMT requires further validation through extended follow-up periods to comprehensively assess long-term outcomes.