FMT rescues mice from DSS-induced colitis in a STING-dependent manner

Autor: Dan Pu, Yao Yao, Chuan Zhou, Ruixian Liu, Zhihong Wang, Yan Liu, Dandan Wang, Binbin Wang, Yaohe Wang, Zhanju Liu, Zhe Zhang, Baisui Feng
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Gut Microbes, Vol 16, Iss 1 (2024)
Druh dokumentu: article
ISSN: 19490976
1949-0984
1949-0976
DOI: 10.1080/19490976.2024.2397879
Popis: Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients’ gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.
Databáze: Directory of Open Access Journals