Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress
Abstract
Colonic goblet cells are specialized epithelial cells that secrete mucus to physically separate the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 enables the production of a thicker and less penetrable mucus layer by reducing endoplasmic reticulum (ER) stress. Accordingly, genetically inhibiting Beclin 1-induced autophagy impairs mucus secretion, while pharmacologically alleviating ER stress results in excessive mucus production. This ER-stress-mediated regulation of mucus secretion is microbiota dependent and requires the Crohn's-disease-risk gene Nod2. Overproduction of mucus alters the gut microbiome, specifically expanding mucus-utilizing bacteria, such as Akkermansia muciniphila, and protects against chemical and microbial-driven intestinal inflammation. Thus, ER stress is a cell-intrinsic switch that limits mucus secretion, whereas autophagy maintains intestinal homeostasis by relieving ER stress.
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BibTeX
@article{naama2026autophagy,
title = {{Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress}},
author = {Maria Naama and Shahar Telpaz and Aya Awad and Shira Ben-Simon and Sarina Harshuk-Shabso and Sonia Modilevsky and Elad Rubin and Jasmin Sawaed and Lilach Zelik and Mor Zigdon and Nofar Asulin and Sondra Turjeman and Michal Werbner and Supapit Wongkuna and Rachel Feeney and Bjoern Schroeder and Abraham Nyska and Meital Nuriel-Ohayon and Shai Bel},
journal = {Cell Host \& Microbe},
year = {2026},
month = sep,
doi = {10.1016/j.chom.2023.01.006},
url = {https://hal.science/hal-05772138v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress
AU - Maria Naama
AU - Shahar Telpaz
AU - Aya Awad
AU - Shira Ben-Simon
AU - Sarina Harshuk-Shabso
AU - Sonia Modilevsky
AU - Elad Rubin
AU - Jasmin Sawaed
AU - Lilach Zelik
AU - Mor Zigdon
AU - Nofar Asulin
AU - Sondra Turjeman
AU - Michal Werbner
AU - Supapit Wongkuna
AU - Rachel Feeney
AU - Bjoern Schroeder
AU - Abraham Nyska
AU - Meital Nuriel-Ohayon
AU - Shai Bel
PY - 2026
DA - 2026/09/30
JO - Cell Host & Microbe
DO - 10.1016/j.chom.2023.01.006
UR - https://hal.science/hal-05772138v1
AB - Colonic goblet cells are specialized epithelial cells that secrete mucus to physically separate the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 enables the production of a thicker and less penetrable mucus layer by reducing endoplasmic reticulum (ER) stress. Accordingly, genetically inhibiting Beclin 1-induced autophagy impairs mucus secretion, while pharmacologically alleviating ER stress results in excessive mucus production. This ER-stress-mediated regulation of mucus secretion is microbiota dependent and requires the Crohn's-disease-risk gene Nod2. Overproduction of mucus alters the gut microbiome, specifically expanding mucus-utilizing bacteria, such as Akkermansia muciniphila, and protects against chemical and microbial-driven intestinal inflammation. Thus, ER stress is a cell-intrinsic switch that limits mucus secretion, whereas autophagy maintains intestinal homeostasis by relieving ER stress.
SN - 1931-3128
ER -