Gut Commensal Antibiotic-Resistant Parabacteroides goldsteinii Ameliorates Mouse Colitis through Valine–Isobutyrate Metabolism

作者：Ningning He, Mengjie Mu, Xiaofang Li, Qingyuan Hao, Kaiwei Chen, Xinnan Zhao, Yang Sun, Haoyu Wang, Zhijun Wu, Hewei Liang, Mengmeng Wang, Liang Xiao, Tao Yu, Zhipeng Wang, Jixing Peng, Yuanqiang Zou, Shangyong Li · 发表于：Research · 年份：2025 · DOI：10.34133/research.0867 · 被引用次数：10 · 研究领域：Gut microbiota and health、Probiotics and Fermented Foods、Clostridium difficile and Clostridium perfringens research

Antibiotic cocktails (ABX) serve as potent therapeutic interventions for refractory ulcerative colitis (UC), yet invariably induce gut dysbiosis. This study demonstrates that pectin oligosaccharides synergistically enhance ABX efficacy by restoring gut microbiota balance and selectively enriched antibiotic-resistant Parabacteroides goldsteinii in a colitis mouse model. Our results further indicate that the gavage administration of P. goldsteinii AM58-2XD markedly alleviated colitis via enhancing the branched-chain amino acid metabolic pathway, particularly by facilitating valine metabolism. Notably, these anticolitis effects were partially attenuated in P. goldsteinii ΔilvE mutants, which are defective in valine-derived isobutyrate (IBN) biosynthesis. We further demonstrated that exogenous IBN supplementation effectively alleviated colitis symptoms in mice and enhanced gut barrier function via activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. Conditional knockout of PPARγ in Caco-2 intestinal epithelial cells markedly abrogated the IBN-induced enhancement of tight junctions, thereby substantiating the critical role of the IBN-PPARγ pathway in metabolite-mediated mucosal repair. Collectively, we delineate a prebiotic/probiotic–metabolite axis wherein P. goldsteinii facilitates mucosal repair via IBN/PPARγ-dependent epithelial metabolic reprogramming. This insight redefines antibiotic-resistant commensals as precise biotherapeutics for microbiota r...