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.

中文翻译：

---

抗生素以不依赖微生物群的方式损害结肠粘液屏障


抗生素的使用是炎症性肠病 （IBD） 发展的危险因素。IBD 的特征是粘液层受损，这不会将肠上皮与微生物群分开。在这里，我们假设抗生素会影响粘液屏障的完整性，从而允许细菌外显并易发生肠道炎症。我们发现抗生素治疗导致结肠粘液屏障破裂和细菌渗透到粘液层中。使用粪便微生物群移植、RNA 测序和机器学习、离体粘液分泌测量和无菌小鼠的抗生素治疗，我们确定抗生素在结肠中诱导内质网应激，从而以微生物群非依赖性方式抑制结肠粘液分泌。这种抗生素诱导的粘液分泌缺陷导致细菌渗透到结肠粘液层，微生物抗原易位到循环中，并在 IBD 小鼠模型中恶化溃疡。因此，抗生素的使用可能通过阻碍粘液产生而易患肠道炎症。