Donor-derived microbial engraftment and gut microbiota shifts associated with weight loss following fecal microbiota transplantation

Abstract

Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis and may provide metabolic benefits for obesity. However, its mechanisms and variability in clinical outcomes remain poorly understood. This 12-week multicenter, single-arm study evaluated the efficacy of FMT for weight loss and explored the role of donor-derived microbial engraftment and functional shifts in mediating weight loss among overweight and obese individuals. Twenty-three participants (body mass index ≥24 kg/m²) without diabetes received three biweekly FMT sessions via a nasojejunal tube. Fecal samples from participants and donors were analyzed using metagenomic sequencing. By week 12, 52% of participants were classified as responders, achieving significant weight loss of ≥5% from baseline, with an average weight loss of 7.98 ± 2.69 kg (P < 0.001). In contrast, non-responders lost 2.90 ± 1.89 kg (P < 0.001). Responders exhibited a significantly higher proportion of donor-derived microbial strains post-FMT compared to non-responders (37.8% vs 15.2%, P = 0.020). Notably, key taxa, including Phascolarctobacterium (P = 0.034) and Acidaminococcaceae (P = 0.012), increased significantly in abundance in responders post-FMT, indicating successful microbial engraftment as a critical determinant of therapeutic success. These findings suggest that FMT is a viable intervention for weight loss in obese individuals. Successful donor-derived microbial engraftment strongly correlates with weight loss efficacy, highlighting the potential of microbiota-targeted therapies in obesity management and providing insights into the mechanisms underlying FMT outcomes.IMPORTANCEPrior research indicates that fecal microbiota transplantation (FMT) is a promising treatment for diseases related to microbiota imbalance, potentially providing metabolic benefits for obesity. However, the specific role of donor-derived microbial engraftment in driving clinical efficacy has remained unclear. In this study, we evaluated the efficacy of FMT in promoting weight loss and explored the role of donor-derived bacterial strains in this process. Our findings demonstrate that the successful engraftment of specific donor-derived taxa, such as Phascolarctobacterium and Acidaminococcaceae, is strongly associated with significant weight loss. This highlights the critical interplay between donor microbiota and recipient gut environment. These findings underscore the potential of microbiota-targeted therapies as a novel strategy for obesity management.CLINICAL TRIALSThis study is registered with the Chinese Clinical Trial Registry as ChiCTR1900024760.

Keywords: fecal microbiota transplantation; gut microbiome; metagenome; obesity.

Fig 1

Study design and primary outcomes. (A) Study design illustrating the recruitment of 10 healthy donors and 25 obese participants. (B and C) Weight and BMI changes in participants at baseline and week 12. Data were analyzed using paired t-tests. ^*P < 0.05, ^**P < 0.01, and ^***P < 0.001.

Fig 2

Gut microbiota assessment of donors and participants. (A) Microbiome composition of donors and participants at different time points. (B and C) Alpha diversity (Shannon and Richness) of the gut microbiome. Individual points represent separate samples. False discovery rate (FDR)-adjusted P values are indicated (^*q < 0.05). (D–G) Principal coordinate analysis (PCoA) of Bray-Curtis dissimilarity data at the species level. FDR-adjusted P values are denoted (^*q < 0.05).

Fig 3

Gut microbiota assessment of donors paired with responders and non-responders. (A) Alpha diversity (Shannon and Richness) of the gut microbiome in donors paired with responders and non-responders. Individual points represent different samples. FDR-adjusted P values are denoted (^*q < 0.05). (B) PCoA of Bray-Curtis dissimilarity data at the species level. FDR-adjusted P values are denoted (^*q < 0.05). (C) Relative abundance of functional pathways in the gut microbiota of donors paired with responders and non-responders. No significant differences were observed, and the top 10 pathways were selected for presentation. Statistical analysis was conducted using independent-sample t-tests and Mann-Whitney U tests.

Fig 4

Strain composition in responders and non-responders at baseline and post-FMT. (A) Strain distribution across groups. “Novel” refers to newly observed strains not matched to recipient baseline or donor strains. “Donor” and “recipient” denote strains unique to donors or recipients, respectively, while “common to donor and recipient” refers to shared strains. (B) Proportion of donor-engrafted strains. Data were analyzed by an independent t-test. (C and D) Multilevel species differences between pre- and post-FMT samples in responders and non-responders were identified using linear discriminant analysis effect size (LEfSe). Taxa were analyzed using a non-parametric Kruskal-Wallis test (P < 0.05, linear discriminant analysis [LDA] score >2).

Fig 5

Shifts in gut microbiome composition toward matched donor following FMT. (A) Heatmap depicting the relative abundance of key taxa. Data were log₁₀-transformed for visualization. (B) The mean relative abundance of Roseburia, Alistipes, Phascolarctobacterium, and Acidaminococcaceae in donors and recipients at baseline and in recipients post-FMT. (C) Relative abundance of Phascolarctobacterium and Acidaminococcaceae in donors and recipients (responders and non-responders) at baseline and post-FMT. The P values were obtained from LEfSe (using non-parametric Kruskal-Wallis tests). (D) Enriched bacterial metabolic pathways in the gut microbiome of responders post-FMT, showing only pathways with statistically significant differences (P < 0.05). Statistical analyses were performed using paired and unpaired t-tests for normally distributed data, and Mann-Whitney U or Wilcoxon signed-rank tests for non-normally distributed data. FDR-adjusted P values are denoted.