Shifts and importance of viable bacteria in treatment of DSS-induced ulcerative colitis mice with FMT

Front Cell Infect Microbiol. 2023 Feb 6:13:1124256. doi: 10.3389/fcimb.2023.1124256. eCollection 2023.

Abstract

Background and aims: Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease.

Methods: We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota.

Results: We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group.

Conclusion: We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.

Keywords: 16S rRNA gene sequencing; DSS-induced colitis; FMT; PMA; viable gut microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria
  • Colitis* / therapy
  • Colitis, Ulcerative*
  • Dextran Sulfate
  • Fecal Microbiota Transplantation
  • Feces / microbiology
  • Humans
  • Mice
  • RNA, Ribosomal, 16S

Substances

  • RNA, Ribosomal, 16S
  • Dextran Sulfate

Grants and funding

This study was funded by National Natural Science Foundation of China (82004433), Science Foundation of Fujian Province in China (2021J011327), Youth Foundation of Fujian Provincial Health Commission (2020QNB060) and Fujian University Industry-University-Research Joint Innovation Project (2022Y4007).