研究动态
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微生物刺激通过胆素信号传导,使肠上皮细胞释放催产素。

Microbial stimulation of oxytocin release from the intestinal epithelium via secretin signaling.

发表日期:2023 Dec
作者: Heather A Danhof, Jihwan Lee, Aanchal Thapa, Robert A Britton, Sara C Di Rienzi
来源: Brain Structure & Function

摘要:

肠道微生物影响肠道和远离肠道的器官的健康。Limosilactobacillus reuteri 是一种人类肠道微生物,能促进正常的肠道传输、抗炎免疫系统、创伤愈合、小鼠中的正常社交行为,以及预防骨质吸收。催产素影响这些功能,催产素信号对于L. reuteri介导的伤口愈合和社交行为至关重要;然而,肠道中导致催产素刺激和有益效果的事件目前尚不明确。在这里,我们通过单细胞RNA-Seq数据集的分析和人类和小鼠肠道组织的成像技术,报道了在肠道上皮中存在进化保守的催产素产生。此外,人类肠道器官样体能够产生催产素,证明肠道上皮足以产生催产素。我们发现L. reuteri能促进人类肠道组织和人类肠道器官样体中的催产素分泌。最后,我们证明L. reuteri刺激催产素分泌与肠道激素分泌素相关,而该激素由肠内分泌细胞产生,而催产素本身则由肠上皮细胞产生。综上所述,本研究表明催产素在肠道上皮中由肠上皮细胞产生和分泌,这是对于L. reuteri刺激分泌素刺激的机制洞察。该研究因此确定了催产素作为一种肠道激素,并提供了肠道微生物促进宿主健康的机制研究。
Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, human intestinal organoids produce oxytocin, demonstrating that the intestinal epithelium is sufficient to produce oxytocin. We find that L. reuteri facilitates oxytocin secretion from human intestinal tissue and human intestinal organoids. Finally, we demonstrate that stimulation of oxytocin secretion by L. reuteri is dependent on the gut hormone secretin, which is produced in enteroendocrine cells, while oxytocin itself is produced in enterocytes. Altogether, this work demonstrates that oxytocin is produced and secreted from enterocytes in the intestinal epithelium in response to secretin stimulated by L. reuteri. This work thereby identifies oxytocin as an intestinal hormone and provides mechanistic insight into avenues by which gut microbes promote host health.