Antibiotics damage the colonic mucus barrier in a microbiota-independent manner, 2024, Jasmin Sawaed et al

Abstract
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. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer.

Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD.

Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.
LINK

 

Another group of chronic diseases that are linked to antibiotic use are IBDs. Recent epidemiological studies have provided a strong link between antibiotic use and risk for development of IBD, in a dose-dependent manner.

Here, we hypothesized that antibiotic use might lead to development of intestinal inflammation by affecting the colonic mucus barrier. The ability of the mucus barrier to provide separation between the host and its gut microbiota is crucial for maintaining gut homeostasis. Breakdown of this barrier is observed both in animal models of IBD and in patients with IBD. As IBDs are characterized by loss of tolerance to the gut microbiota, it is thought that impairment of the protective mucus barrier can drive these diseases. Without a proper mucus barrier, the microbes come in close contact with host tissues, triggering an immune response.

We found that short-term oral antibiotic treatment was sufficient to impair the separation between host and microbiota in the colon. This phenomenon was true for all the antibiotics we tested.