Real-world of Limosilactobacillus reuteri in mitigation of acute experimental colitis

作者：Ningning Yue, Hailan Zhao, Peng Hu, Yuan Zhang, Cheng‐mei Tian, Kong Chen, Zhiliang Mai, Longbin Huang, Qianjun Luo, Daoru Wei, Ruiyue Shi, Shao-Hui Tang, Yuqiang Nie, Yujie Liang, Jun Yao, Lisheng Wang, Defeng Li · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03158-8 · 被引用次数：26 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research、Infant Nutrition and Health

Probiotics have been proposed as a potential strategy for managing ulcerative colitis (UC). However, the underlying mechanisms mediating microbiota-host crosstalk remain largely elusive. Here, we report that Limosilactobacillus reuteri (L. reuteri), as a probiotic, secretes cytoplasmic membrane vesicles (CMVs) that communicate with host cells, alter host physiology, and alleviate dextran sulfate sodium (DSS)-induced colitis. First, L. reuteri-CMVs selectively promoted the proliferation of the beneficial bacterium Akkermansia muciniphila (AKK) by upregulating the expression of glycosidases (beta-N-acetylhexosaminidase and alpha-N-acetylglucosaminidase) involved in glycan degradation and metabolic pathways and restored the disrupted gut microbiota balance. Second, L. reuteri-CMVs were taken up by intestinal epithelial cells (IECs), elevated the expression of ZO-1, E-cadherin (Cdh1), and Occludin (Ocln), decreased intestinal permeability, and exerted protective effects on epithelial tight junction functionality. RNA sequencing analysis demonstrated that L. reuteri-CMVs repaired intestinal barrier by activating the HIF-1 signaling pathway and upregulating HMOX1 expression. Third, L. reuteri-CMVs increased the population of double positive (DP) CD4+CD8+ T cells in the intestinal epithelial layer, suppressing gut inflammation and maintaining gut mucosal homeostasis. Finally, L. reuteri-CMVs exhibited satisfactory stability and safety in the gastrointestinal tract and specifically t...