Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging

Liang Sun*, Zhiming Li, Caiyou Hu, Jiahong Ding, Qi Zhou, Guofang Pang, Zhu Wu, Ruiyue Yang, Shenghui Li, Jian Li, Jianping Cai, Yuzhe Sun, Rui Li, Hefu Zhen, Shuqin Sun, Jianmin Zhang, Mingyan Fang, Zhihua Chen, Yuan Lv, Qizhi CaoYanan Sun, Ranhui Gong, Zezhi Huang, Yong Duan, Hengshuo Liu, Jun Dong, Junchun Li, Jie Ruan, Haorong Lu, Benjin He, Ninghu Li, Tao Li, Wenbin Xue, Yan Li, Juan Shen, Fan Yang, Cheng Zhao, Qinghua Liang, Mingrong Zhang, Chen Chen, Huan Gong, Yong Hou, Jian Wang, Ying Zhang, Huanming Yang, Shida Zhu, Liang Xiao, Zhen Jin, Haiyun Guo, Peng Zhao, Susanne Brix, Xun Xu, Huijue Jia, Karsten Kristiansen, Ze Yang, Chao Nie

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.

Original languageEnglish
Article numbere14028
JournalAging Cell
Volume22
Issue number12
Number of pages20
ISSN1474-9718
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Keywords

  • aging
  • gut microbiota
  • renal function
  • serum metabolome

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