Intestinal mucins play a crucial role in the mucosal barrier, serving as the body's initial defense against microorganisms. However, how the host regulates the secretion and glycosylation of these mucins in response to bacterial invasion remains unclear. Our study demonstrates that when exposed to Streptococcus gallolyticus (SGG), a gut pathobiont, the host mucosa promptly adjusts the behavior of specialized goblet cells (GCs) located in the middle of the crypts. A subset of these cells undergoes a remodeling, becoming intercrypt goblet cells (icGCs), which do not detach from the surface but instead migrate along intercrypt spaces while secreting a mucus impermeable to bacterial pathogens. Significantly, a non-piliated SGG mutant unable to bind to mucus fails to induce icGCs, allowing its translocation through the mucosa and submucosa. Interestingly, a closely related nonpathogenic bacterium, SGM, able to bind to mucus, also triggers the differentiation of GCs into icGCs. This discovery opens new avenues for treating patients with a "leaky gut" as observed in intestinal diseases such as inflammatory bowel diseases and metabolic disorders, but also patients with a history of repeated antibiotic use. Utilizing mucus-adherent probiotics to induce icGCs represents a promising strategy for reinforcing the mucosal barrier.

中文翻译：

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细菌感染后隐窝杯状细胞的诱导：恢复粘膜屏障的有前途的治疗靶点。


肠道粘蛋白在粘膜屏障中起着至关重要的作用，是身体抵御微生物的初始防御。然而，宿主如何调节这些粘蛋白的分泌和糖基化以响应细菌入侵仍不清楚。我们的研究表明，当暴露于肠道致病菌没食子溶性链球菌 （SGG） 时，宿主粘膜会迅速调整位于隐窝中间的特殊杯状细胞 （GC） 的行为。这些细胞的一个子集经历重塑，成为加密杯状细胞 （icGC），它们不会从表面分离，而是沿着加密间隙迁移，同时分泌对细菌病原体不透性的粘液。值得注意的是，无法与粘液结合的非毛化 SGG 突变体无法诱导 icGCs，允许其通过粘膜和粘膜下层易位。有趣的是，一种密切相关的非致病性细菌 SGM 能够与粘液结合，也触发 GC 分化为 icGC。这一发现为治疗在炎症性肠病和代谢紊乱等肠道疾病中观察到的“肠漏”患者开辟了新的途径，也为治疗有反复使用抗生素史的患者开辟了新的途径。利用粘液粘附益生菌诱导 icGC 代表了加强粘膜屏障的一种有前途的策略。