Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense

Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense

Abstract Older individuals experience increased susceptibility and mortality to bacterial infections, but the underlying etiology remains unclear. Herein, it is shown that aging‐associated reduction of commensal Parabacteroides goldsteinii (P. goldsteinii) in both aged mice and humans critically con...

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Main Authors: Peng Gu, Rongjuan Wei, Ruofan Liu, Qin Yang, Yuxuan He, Jianbin Guan, Wenhao He, Jiaxin Li, Yunfei Zhao, Li Xie, Jie He, Qingling Guo, Jiajia Hu, Jingna Bao, Wandang Wang, Jiayin Guo, Zhenhua Zeng, Zhongqing Chen, Yong Jiang, Zhanguo Liu, Peng Chen
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Advanced Science
Subjects:
aging
bacterial infection
gut microbiome
macrophage
Online Access:https://doi.org/10.1002/advs.202411008
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Summary:Abstract Older individuals experience increased susceptibility and mortality to bacterial infections, but the underlying etiology remains unclear. Herein, it is shown that aging‐associated reduction of commensal Parabacteroides goldsteinii (P. goldsteinii) in both aged mice and humans critically contributes to worse outcomes of bacterial infection. The colonization of live P. goldsteinii conferred protection against aging‐associated bacterial infections. Metabolomic profiling reveals a protective compound, apigenin, generated by P. goldsteinii, antagonizes bacterial clearance defects in aged mice. AMP‐binding protein (ampB) is identified as a key gene involved in apigenin synthesis in P. goldsteinii using homologous recombination in bacteria. Mechanistically, apigenin binds directly to the potential sites on Fgr (M341 and D404), preventing its inhibitory role on Vav1 phosphorylation, and therefore promoting the activation of Cdc42/Rac1, Arp2/3 expression and subsequent actin reorganization, which contributes to the enhanced phagocytosis of macrophages to bacteria. Collectively, the findings suggest that dysbiosis of the gut microbiota may impair host defense mechanisms and increase susceptibility to bacterial infections in older adults and highlight the microbiota‐apigenin‐Fgr axis as a possible route to ameliorate aging‐associated antibacterial defects.
ISSN:2198-3844

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