FMT rescues mice from DSS-induced colitis in a STING-dependent manner
Dan Pu,
Yao Yao,
Chuan Zhou,
Ruixian Liu,
Zhihong Wang,
Yan Liu,
Dandan Wang,
Binbin Wang,
Yaohe Wang,
Zhanju Liu,
Zhe Zhang,
Baisui Feng
Affiliations
Dan Pu
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Yao Yao
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Chuan Zhou
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Ruixian Liu
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Zhihong Wang
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Yan Liu
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Dandan Wang
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Binbin Wang
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Yaohe Wang
National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
Zhanju Liu
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Zhe Zhang
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Baisui Feng
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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.
