Clostridium butyricum Restores Intestinal Barrier Integrity via the IL-22/Reg3 Pathway Following Traumatic Brain Injury in Mice

作者：Min Liu, Min Liu, Ying Pang, Ying Pang, Li Xu, Li Xu, Tongjie Ji, Junyu Yang, Dan Huang, Meng Cheng, M H Chen, Bingsong Huang, Siyi Xu, Kaijun Zhao, Jing Zhang, Takehiko Yokomizo, Chunlong Zhong · 发表于：Journal of Neurotrauma · 年份：2025 · DOI：10.1177/08977151251367404 · 被引用次数：5 · 研究领域：Gut microbiota and health、Enhanced Recovery After Surgery、Clostridium difficile and Clostridium perfringens research

Traumatic brain injury (TBI) disrupts the intestinal barrier, linking brain trauma to systemic inflammation and secondary complications. This study investigated the role of gut microbiota and its metabolites in intestinal barrier dysfunction following TBI, using a controlled cortical impact mouse model. TBI-induced gut dysbiosis was characterized by reduced microbial diversity and a loss of butyrate-producing bacteria, which led to decreased levels of short-chain fatty acids (SCFAs), particularly butyric acid. This disruption compromised the interleukin-22/regenerating islet-derived protein 3 (IL-22/Reg3) signaling pathway, which is essential for maintaining gut barrier integrity. Supplementation with Clostridium butyricum restored butyric acid production, enhanced IL-22/Reg3 expression, and alleviated TBI-induced intestinal permeability. These findings identify the SCFA/IL-22/Reg3 axis as a key mediator of gut barrier homeostasis after TBI and highlight the potential therapeutic role of butyrate-producing probiotics in managing TBI-associated intestinal complications.