Fecal Microbiota Transplantation by Rectal Enema Improves Short-Term Insulin Resistance in Metabolic Syndrome: A Pilot Randomized Controlled Trial

Abstract

Background: The gut microbiota plays a vital role in various physiological processes, including metabolism. Fecal microbiota transplantation (FMT) involves transferring fecal matter from a healthy donor to rebalance a patient's intestinal dysbiosis. The impact of FMT on metabolic syndrome (MetS) is subject to debate. This study assesses the effects of FMT on MetS when administered by rectal enema.

Methods: In a double-blind, randomized controlled trial, subjects with MetS were assigned to receive either FMT (n=8) or a sham intervention (n=10) via rectal enema. Participants were followed at 6 and 12 weeks. The primary outcome was changes in the homeostatic model assessment of insulin resistance (HOMA-IR). Secondary outcomes included fasting blood glucose (FBG), body mass index (BMI), inflammatory markers, and hepatic steatosis. The mean adjusted difference (MAD) and 95% confidence interval (CI) between groups were reported as treatment effects using a linear marginal model for repeated measures.

Results: The study included patients with a mean age of 50.4±10.7 years. Baseline BMI and HOMA-IR were similar between groups. Over 6 weeks, FMT significantly improved HOMA-IR (MAD, -1.63; 95% CI, -2.63 to -0.64; P=0.001). The FMT group also showed improvements in serum FBG and high-sensitivity C-reactive protein compared with levels in the sham group (P=0.044 and P=0.025, respectively). However, no significant changes in MetS-associated variables or liver steatosis were evident at 12 weeks. Stool microbiota analysis revealed a reduced relative abundance of Desulfovibrio, Bacteroides, and Parabacteroides after FMT.

Conclusion: FMT by rectal enema produced favorable changes in IR in patients with MetS. FMT may be an effective treatment for patients with metabolism-related diseases. Further research into the long-term benefits of the procedure is warranted.

Keywords: Dysbiosis; Fecal microbiota transplantation; Insulin resistance; Metabolic syndrome.

Figure 1

Consolidated Standards of Reporting Trials (CONSORT) diagram of study flow. FMT, fecal microbiota transplantation.

Figure 2

Box plot of metabolic parameters between interventions at baseline, 6-, and 12-week. (A) Homeostatic model assessment for insulin resistance (HOMA-IR), (B) fasting blood glucose, (C) triglyceride, and (D) low-density lipoprotein cholesterol (LDL-C). FMT, fecal microbiota transplantation; MAD, mean adjusted difference; CI, confidence interval.

Figure 3

Differences in alpha diversity indexes between pre- and post-intervention. (A) Fecal microbiota transplantation (FMT) group and (B) sham group (P<0.05 is considered significant).

Figure 4

Microbiota profile of gut microbiota and microbial colonization: (A) Phyla and (B) genus.