Antibiotics damage the colonic mucus barrier in a microbiota-independent manner.

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation.

Salmonella manipulates the host to drive pathogenicity via induction of interleukin 1β.

Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β production is detrimental during Salmonella infection.

Autophagy-ER stress crosstalk controls mucus secretion and susceptibility to gut inflammation.

Mucus secretion from colonic goblet cells is an important host defense mechanism against the harsh lumenal environment. Yet how mucus secretion is regulated is not well understood. We discovered that constitutive activation of macroautophagy/autophagy via BECN1 (beclin 1) relieves endoplasmic reticulum (ER) stress in goblet cells, which in turn produce a thicker and less penetrable mucus barrier.

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

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.

Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome.

Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infuse gut organ cultures with longitudinal microbiota samples collected from therapy-naive patients with irritable bowel syndrome (IBS) under a low-fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diet.