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

The NHC Key Laboratory of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, China. BGI Research, Shenzhen, China. China National GeneBank, BGI Research, Shenzhen, China. Shenzhen Key Laboratory of Neurogenomics, BGI Research, Shenzhen, China. State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, and Human Phenome Institute, Fudan University, Shanghai, China. Jiangbin Hospital, Nanning, China. Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China. School of Gerontology, Binzhou Medical University, Yantai, China. Office of Longevity Cultural, People's Government of Yongfu County, Guilin, China. Yunnan Key Laboratory of Laboratory Medicine, Kunming, China. Yunnan Institute of Experimental Diagnosis, Kunming, China. Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, BGI Research, Shenzhen, China. Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI Research, Shenzhen, China. Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark. Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research, Shenzhen, China. Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark. Qingdao-Europe Advanced Institute for Life Sciences, Qingdao, Shandong, China.

Aging cell. 2023;(12):e14028
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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.