Le Cosquer Guillaume, Pannier Melissa, Meunier Elodie, Thevenin Julie, Pyhourquet Elise, Guyonnet Sophie, Vellas Bruno, Santin Yohan, Guiard Bruno, Parini Angelo, Buscail Louis, Bournet Barbara, Guillemet Damien, Deraison Celine, Vergnolle Nathalie, Motta Jean-Paul
Institute of Digestive Health Research (IRSD), INSERM, Toulouse University, INRAe, ENVT, University Toulouse III Paul Sabatier (UPS), Toulouse, France.
Department of Gastroenterology and Pancreatology, Toulouse University Hospital (CHU Toulouse), Toulouse, France and Toulouse University, University Toulouse III Paul Sabatier (UPS), Toulouse, France.
NPJ Biofilms Microbiomes. 2025 May 22;11(1):84. doi: 10.1038/s41522-025-00716-8.
Pathophysiological mechanisms of unhealthy aging, particularly the transition from robustness to frailty, remain poorly understood. Despite extensive microbiome research on taxonomy, the behavior of early prefrail gut bacteria in their natural community-host mucosal tissue context remains unexplored. Using fecal samples from the INSPIRE-T aging human cohort, we characterized gut microbiota phenotype during prefrailty stages using a polymicrobial biofilm model. Results revealed that prefrail-derived biofilms exhibited distinct taxonomic and physical alterations, enhanced dispersal, and increased epithelial virulence compared to robust counterparts. Multiparametric analyses linked biofilm characteristics to clinical traits, suggesting their potential as aging status indicators. Polyphenol-rich grape pomace extract partially reversed prefrail biofilm alterations and reduced proinflammatory prefrail biofilm responses in vitro. Microbiota from prefrail-aged mice induced colon damage in antibiotic-treated recipients, establishing a prefrail microbiome-inflammation causality. Overall, the findings identified novel prefrail microbiome characteristics, established causal inflammatory links, and supported microbiota-targeted geroprotective interventions for the prefrail populations.
不健康衰老的病理生理机制，尤其是从强健到虚弱的转变，仍知之甚少。尽管对微生物组进行了广泛的分类学研究，但在自然群落-宿主黏膜组织环境中，早期虚弱前期肠道细菌的行为仍未得到探索。我们使用INSPIRE-T衰老人类队列的粪便样本，通过多微生物生物膜模型对虚弱前期阶段的肠道微生物群表型进行了表征。结果显示，与强健个体的对应物相比，虚弱前期来源的生物膜表现出明显的分类学和物理变化、更强的扩散能力以及更高的上皮毒性。多参数分析将生物膜特征与临床特征联系起来，表明它们有可能作为衰老状态指标。富含多酚的葡萄渣提取物部分逆转了虚弱前期生物膜的变化，并在体外降低了促炎的虚弱前期生物膜反应。虚弱前期小鼠的微生物群在抗生素处理的受体中诱发了结肠损伤，确立了虚弱前期微生物组与炎症之间的因果关系。总体而言，这些发现确定了新的虚弱前期微生物组特征，建立了因果性炎症联系，并支持针对虚弱前期人群的以微生物群为靶点的老年保护干预措施。
