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Age-related compositional changes and correlations of gut microbiome, serum metabolome, and immune factor in rats

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Abstract

Aging is a complex physiological process associated with degenerative disorder of metabolism and immune function, which contributes to the occurrence of senile diseases. The gut microbiota affects systemic inflammation in aging processes probably through metabolism, but their relationship is still unclear. In this study, 16S-rRNA-sequencing technology, gas chromatography-time-of-flight mass spectrometry (GC-TOFMS)–based metabolic profiling, and immune factor analysis combined with advanced differential and association analysis were employed to investigate the correlation between the microbiome, metabolome, and immune factors in male Wistar rats across lifespan. Our findings showed significant changes in the ileum microbiome and serum metabolome compositions across aging process. A two-level strategy was applied to demonstrate that key metabolites associated with age such as 4-hydroxyproline, proline, and lysine were clustered together and positively correlated with beneficial microbes including Bifidobacterium, Lactobacillus, and Akkermansia. Function analysis explored association between serum metabolite class and specific gut bacteria’s metabolism pathways. Further correlation analysis on all the alteration patterns provided an interaction network of main immune factors such as IL-10, IgA, IgM, and IgG with key gut bacteria and serum metabolites. This study offers new insights into the relationship between immune factors, serum metabolome, and the gut microbiome.

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Funding

This work was financially supported by Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao TongUniversity (YG2016MS40, YG2017MS28), the National Nature Science Foundation of China (30901997 and 31972935), and the National Basic Research Program of China (2012CB910102).

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Author notes

  1. Xia Zhang, Yuping Yang, and Juan Su equally contributed to this study as first authors.

Authors and Affiliations

  1. Key Laboratory of Systems Biomedicine(Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xia Zhang, Yuping Yang, Chongchong Wang, Shaoqiu Chen, Yingfang Lv & Xiaoyan Wang

  2. College of Veterinary Medicine, Nanjing Agriculture University, Nanjing, 210095, China

    Juan Su & Shihao Fan

  3. Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

    Xiaojiao Zheng, Jiajian Liu, Aihua Zhao, Tianlu Chen & Wei Jia

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  1. Xia Zhang
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Correspondence to Tianlu Chen, Wei Jia or Xiaoyan Wang.

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All experiments were carried out strictly in accordance with recommendations on the National Institutes of Health’s Guide for Care and Use of Laboratory Animals. The experimental program was approved by the Center for Laboratory Animals of Shanghai Jiao Tong University.

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Zhang, X., Yang, Y., Su, J. et al. Age-related compositional changes and correlations of gut microbiome, serum metabolome, and immune factor in rats. GeroScience 43, 709–725 (2021). https://doi.org/10.1007/s11357-020-00188-y

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