Mapping the gut microbial structural variations in healthy aging within the Chinese population

Area of Science:

• Microbiology
• Genomics
• Gerontology

Background:

• Gut microbiome structural variants (SVs) are increasingly recognized for their role in host health.
• Understanding SVs during human aging is crucial for deciphering the microbiome's impact on healthy aging and age-related diseases.

Purpose of the Study:

• To characterize gut microbial SVs in a large cohort of Chinese participants.
• To identify SVs associated with aging, healthy aging, and age-related chronic diseases.
• To elucidate the mechanistic links between specific SVs, diet, metabolism, and aging outcomes.

Main Methods:

• Whole-genome sequencing of gut microbial communities from 3,230 Chinese participants.
• Bioinformatic analysis to identify and quantify microbial structural variants (SVs).
• Statistical association analyses to link SVs with aging status, healthspan, and disease phenotypes.

Main Results:

• Identified key gut microbial SVs associated with aging, healthy aging, and age-related diseases.
• Observed a pattern of copy number loss in aging-related SVs, with 35 core SVs consistently detected.
• Discovered eight SVs that differentiate healthy from unhealthy aging, irrespective of chronological age.
• A specific 3-kbp deletion SV in Bifidobacterium pseudocatenulatum, involved in plant polysaccharide degradation, was linked to a plant-based diet, bile acid metabolism, and healthy aging.
• Connected SVs to chronic kidney disease through genes in the methionine-homocysteine pathway.

Conclusions:

• Gut microbial SVs are significant biomarkers and potential mediators of human aging.
• Dietary patterns, particularly plant-based diets, influence SVs related to healthy aging.
• Targeting specific microbial SVs and their metabolic functions may offer novel strategies for enhancing healthspan and longevity.