Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse

Yapeng Yang1, Xiaojiao Zheng2, Yuqing Wang1

  • 1College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.

Insights

Fecal microbiota transplantation (FMT) from healthy donors effectively treats colitis symptoms and inflammation in mice. This approach shows promise for inflammatory bowel disease (IBD) by restoring beneficial gut bacteria and metabolites.

Area of Science:

  • Gastroenterology and Immunology
  • Microbiome Research
  • Translational Medicine

Background:

  • Fecal microbiota transplantation (FMT) is utilized in clinical practice for inflammatory bowel disease (IBD), yet donor selection and underlying mechanisms require further investigation.
  • Dextran sodium sulfate (DSS)-induced colitis in mice serves as a model to evaluate FMT efficacy and donor-specific effects on gut health.

Purpose of the Study:

  • To compare the protective effects of FMT from healthy donors (HD) versus ulcerative colitis (UC) donors on colitis symptoms, inflammation, and intestinal barrier integrity in a mouse model.
  • To elucidate the mechanistic differences, including microbial composition and metabolite profiles, associated with effective FMT interventions in IBD.

Main Methods:

  • Induction of colitis in mice using DSS, followed by FMT administration from either healthy or UC donors.
  • Assessment of colitis symptoms, inflammatory markers (MPO, EPO), and anti-inflammatory cytokines (IL-10).
  • Metagenomic sequencing to analyze gut microbial composition and diversity.
  • Metabolomics analysis to identify key metabolic pathways and compounds modulated by FMT.

Main Results:

  • FMT from healthy donors significantly alleviated colitis symptoms, reduced inflammatory markers (MPO, EPO), and increased IL-10 levels compared to UC donor FMT.
  • HD-FMT enriched beneficial bacteria like *Alistipes putredinis*, *Akkermansia muciniphila*, and SCFA/SBA producers, while UC-FMT increased IBD-associated bacteria.
  • HD-FMT led to increased levels of anti-inflammatory compounds such as indoleacetic acid and unsaturated fatty acids (DHA, DPA, EPA).

Conclusions:

  • FMT can effectively alleviate colitis symptoms, with healthy donor FMT demonstrating superior therapeutic effects compared to UC donor FMT.
  • The beneficial effects of HD-FMT are associated with restored microbial diversity, enrichment of anti-inflammatory bacteria, and modulation of host metabolism.
  • This study provides critical insights into the mechanisms of FMT in IBD and supports the importance of donor selection for therapeutic efficacy.