Fecal Microbiota Transplantation for Ulcerative Colitis Using Dai and Han Donors

This randomized, parallel-group clinical study investigates the efficacy and mechanisms of fecal microbiota transplantation (FMT) using healthy donors from the Dai nationality versus Han nationality for treating ulcerative colitis (UC).

Background: UC is a chronic relapsing inflammatory bowel disease characterized by colonic mucosal inflammation. FMT has emerged as a promising therapeutic strategy by reconstructing intestinal microbiota. Preliminary findings indicate that FMT using donors from the Dai ethnic group in Yunnan Province (who have unique dietary and lifestyle habits) may achieve superior clinical remission compared to Han donors. This study aims to validate this observation and identify the core metabolites and key gut microbiota responsible for the enhanced efficacy.

Study Design: A total of 200 UC patients (aged 18-60 years, Mayo score 3-10, left-sided colitis) will be enrolled and randomly allocated into two groups (n=100 each): (1) FMT with healthy Han donors; (2) FMT with healthy Dai donors. Donors will be healthy individuals aged 18-23 years screened according to AGA guidelines.

Intervention: Patients will receive FMT via transendoscopic enteral tubing (TET) at 60 mL per infusion, once every 3 days for a total of 3 times.

Outcome Measures: Primary efficacy is clinical remission at week 12 (Mayo total score ≤2, no individual subscore >1, endoscopic subscore decreased by ≥1 from baseline). Secondary endpoints include Mayo score, MES, histopathology (HE staining), fecal calprotectin, CRP, ESR, and intestinal mucosal barrier function.

Mechanistic Investigations: Donor and recipient stool samples will be collected before FMT and at weeks 1 and 12 post-FMT. Metabolomics (LC-MS/MS, GC-MS) and metagenomic sequencing will identify differential metabolites and key bacterial taxa. Co-occurrence and metabolic complementarity networks will identify keystone species. Correlation analysis will reveal functional microbial groups. In vitro and in vivo experiments will validate the anti-inflammatory effects of identified key bacteria and metabolites.

Significance: This study will elucidate why Dai donors may confer superior FMT outcomes and identify transplantable microbial signatures and bioactive metabolites for UC therapy.

Inclusion criteria

• Age 18-60 years
• Diagnosed with ulcerative colitis (left-sided colitis) according to ECCO guidelines and Chinese Guidelines for the Diagnosis and Treatment of Ulcerative Colitis (2023 Xi'an)
• Baseline Mayo score 3-10
• Treated only with mesalazine before and during the study to exclude drug interference

Exclusion criteria

• Pregnancy or planned pregnancy in the near future
• Patients in clinical remission (Mayo score ≤2 with no individual subscore >1)
• Development of diseases different from or confounding the initial diagnosis during the study
• History of toxic megacolon, perianal disease, or intestinal surgery
• Concurrent severe cardiac, pulmonary, or renal disease, or malignancy