Multi-omics insights implicate the remodeling of the intestinal structure and microbiome in aging

Shaohua Chen; Chengbang Wang; Xiong Zou; Hanwen Li; Guanglin Yang; Xiaotao Su; Zengnan Mo

doi:10.3389/fgene.2024.1450064

Multi-omics insights implicate the remodeling of the intestinal structure and microbiome in aging

Front Genet. 2024 Nov 12:15:1450064. doi: 10.3389/fgene.2024.1450064. eCollection 2024.

Authors

Shaohua Chen^#^{1

2}, Chengbang Wang^#², Xiong Zou², Hanwen Li², Guanglin Yang^{1

2}, Xiaotao Su^{2

3}, Zengnan Mo^{2

4}

Affiliations

¹ Department of Urology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
² Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.
³ Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, China.
⁴ Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, China.

^# Contributed equally.

Abstract

Background: Aging can impair the ability of elderly individuals to fight infections and trigger persistent systemic inflammation, a condition known as inflammaging. However, the mechanisms underlying the development of inflammaging remain unknown.

Methods: We conducted 16S rRNA sequencing of intestinal contents from young and old C57BL/6J mice to elucidate changes in gut microbiota diversity and microbial community composition after aging. Aging-related differential bacterial taxa were then identified, and their abundance trends were validated in human samples. The variances in intestinal barrier function and circulating endotoxin between groups were also assessed. Furthermore, widely targeted metabolomics was conducted to characterize metabolic profiles after aging and to investigate the key metabolic pathways enriched by the differential metabolites.

Results: Our findings demonstrated an increase in relative proportion of pathogenic bacteria with age, a trend also revealed in healthy populations of different age groups. Additionally, aging individuals exhibited reduced intestinal barrier function and increased circulating endotoxin levels. Widely targeted metabolomics revealed a significant increase in various secondary bile acid metabolites after aging, positively correlated with the relative abundance of several aging-related bacterial taxa. Furthermore, old group had lower levels of various anti-inflammatory or beneficial metabolites. Enrichment analysis identified the starch and sucrose metabolism pathway as potentially the most significantly impacted signaling pathway during aging.

Conclusion: This study aimed to provide insights into the complex interactions involved in organismal inflammaging through microbial multi-omics. These findings lay a solid foundation for future research aimed at identifying novel biomarkers for the clinical diagnosis of aging-related diseases or potential therapeutic targets.

Keywords: aging; gut microbiota; inflammaging; intestinal epithelial cells; metabolism.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by Youth Program of Scientific Research Foundation of Guangxi Medical University Cancer Hospital (Grant No. 2023-02), Guangxi Research Foundation for Basic Capability Improvement of Young and Middle-aged Teachers in Universities (Grant No. 2024KY0124), Guangxi Key Research and Development Project (Grant No. Guike AB21196022), Guangxi Science and Technology Major Project (Grant No. Guike AA22096032), Guangxi Science and Technology Major Project (Grant No. Guike AA22398), The National Natural Science Foundation of China (82270806), Major Project of Guangxi Innovation Driven (AA18118016), Guangxi key Laboratory for Genomic and Personalized Medicine (Grant number 22-35-17).