The report published in Science Advances suggested that antibiotic use increases the risk of inflammatory bowel disease (IBD; e.g., Crohn’s disease and ulcerative colitis), which affect about 1% of the global population.
Shai Bel, PhD, and his research team at the Azrieli Faculty of Medicine of Bar-Ilan University raised the possibly that their discovery could upend the understanding of antibiotic effects and IBD development.
IBD involves erosion of the mucosal layer that serves as a critical barrier between the gut microbiome and the immune system, but the exact causes of the disease remain unclear, although some studies have indicated a link between antibiotic use and an increased risk of developing IBD.
“We have discovered that antibiotic use actually damages the protective mucus layer that separates the immune system in the gut from the microbiome,” Dr. Bel explained. The results of the study indicated that antibiotics, whether administered orally or via injection, disrupt the mucus layer, facilitating bacterial penetration and increasing the risk of gut inflammation.
The report in Science Advances described how the researchers used a bacteria-free mouse model, antibiotic treatment, fecal microbiota transplant, RNA sequencing followed by machine learning, and ex vivo mucus secretion measurements to determine 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,” the researchers explained. “Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.”
The study pointed out that the use of antibiotics is so prolific in both medicine and agriculture that resistant microbes have arisen, adding that the extensive use “is based on the assumption that, other than toxicity issues when used in large doses, antibiotics disrupt biological processes in microbes and not the host. Yet, recent research in germ-free (GF) animals is beginning to uncover the overlooked effects that antibiotics have on the host.”
The researchers also question the link between antibiotic-induced alteration to the gut microbiota and other diseases such as obesity and diabetes.
Dr. Bel calls “striking” the finding that “antibiotics” impact on the mucus barrier is not due to alterations in the microbiome but rather affects the cells in the intestinal wall responsible for mucus production. Dr. Bel added, “This finding shatters the paradigm that antibiotics harm only bacteria and not our own cells.”
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