Open AccessFoxo1 controls gut homeostasis and commensalism by regulating mucus secretion
Author(s) -
Zuojia Chen,
Jialie Luo,
Jian Li,
Girak Kim,
Eric S. Chen,
Sheng Xiao,
Scott B. Snapper,
Bin Bao,
Dingding An,
Richard S. Blumberg,
Cheng Hui Lin,
Sui Wang,
Jiaxin Zhong,
Kuai Liu,
Qiyuan Li,
Chuan Wu,
Vijay K. Kuchroo
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20210324
Subject(s) - mucus , goblet cell , secretion , biology , foxo1 , microbiology and biotechnology , dysbiosis , homeostasis , intestinal mucosa , microbiome , immunology , gut flora , epithelium , signal transduction , endocrinology , medicine , bioinformatics , ecology , genetics , protein kinase b
Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.