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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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411008 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Peng Gu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-45638ec9ca5e4085873ce4e9794c3546 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-45638ec9ca5e4085873ce4e9794c35462025-08-20T01:49:41ZengWileyAdvanced Science2198-38442025-03-011212n/an/a10.1002/advs.202411008Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial DefensePeng Gu0Rongjuan Wei1Ruofan Liu2Qin Yang3Yuxuan He4Jianbin Guan5Wenhao He6Jiaxin Li7Yunfei Zhao8Li Xie9Jie He10Qingling Guo11Jiajia Hu12Jingna Bao13Wandang Wang14Jiayin Guo15Zhenhua Zeng16Zhongqing Chen17Yong Jiang18Zhanguo Liu19Peng Chen20Department of Critical Care Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Critical Care Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaDepartment of Critical Care Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Critical Care Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaDepartment of Critical Care Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Critical Care Medicine Nanfang Hospital Southern Medical University Guangzhou 510510 ChinaDepartment of Clinical Medicine Laboratory Affiliated Xiaolan Hospital Southern Medical University Zhongshan 528415 ChinaNMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Critical Care Medicine Nanfang Hospital Southern Medical University Guangzhou 510510 ChinaDepartment of Critical Care Medicine Nanfang Hospital Southern Medical University Guangzhou 510510 ChinaDepartment of Pathophysiology Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Critical Care Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaDepartment of Critical Care Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaAbstract 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.https://doi.org/10.1002/advs.202411008agingbacterial infectiongut microbiomemacrophage |
| spellingShingle | 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 Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense Advanced Science aging bacterial infection gut microbiome macrophage |
| title | Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense |
| title_full | Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense |
| title_fullStr | Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense |
| title_full_unstemmed | Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense |
| title_short | Aging‐induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense |
| title_sort | aging induced alternation in the gut microbiota impairs host antibacterial defense |
| topic | aging bacterial infection gut microbiome macrophage |
| url | https://doi.org/10.1002/advs.202411008 |
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