Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress.

Cell host & microbe 2023 Mar 08

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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. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Maria Naama, Shahar Telpaz, Aya Awad, Shira Ben-Simon, Sarina Harshuk-Shabso, Sonia Modilevsky, Elad Rubin, Jasmin Sawaed, Lilach Zelik, Mor Zigdon, Nofar Asulin, Sondra Turjeman, Michal Werbner, Supapit Wongkuna, Rachel Feeney, Bjoern O Schroeder, Abraham Nyska, Meital Nuriel-Ohayon, Shai Bel. Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress. Cell host & microbe. 2023 Mar 08;31(3):433-446.e4