Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes

Aarthi Ravikrishnan, Indrik Wijaya, Eileen Png, Kern Rei Chng, Eliza Xin Pei Ho, Amanda Hui Qi Ng, Ahmad Nazri Mohamed Naim, Jean-Sebastien Gounot, Shou Ping Guan, Jasinda Lee Hanqing, Lihuan Guan, Chenhao Li, Jia Yu Koh, Paola Florez Sessions, Woon-Puay Koh, Lei Feng, Tze Pin Ng, Anis Larbi, Andrea B. Maier, Brian K. Kennedy and Niranjan Nagarajan ()
Additional contact information
Aarthi Ravikrishnan: Agency for Science, Technology and Research (A*STAR)
Indrik Wijaya: Agency for Science, Technology and Research (A*STAR)
Eileen Png: Agency for Science, Technology and Research (A*STAR)
Kern Rei Chng: Agency for Science, Technology and Research (A*STAR)
Eliza Xin Pei Ho: Agency for Science, Technology and Research (A*STAR)
Amanda Hui Qi Ng: Agency for Science, Technology and Research (A*STAR)
Ahmad Nazri Mohamed Naim: Agency for Science, Technology and Research (A*STAR)
Jean-Sebastien Gounot: Agency for Science, Technology and Research (A*STAR)
Shou Ping Guan: National University of Singapore
Jasinda Lee Hanqing: National University of Singapore
Lihuan Guan: National University of Singapore
Chenhao Li: Agency for Science, Technology and Research (A*STAR)
Jia Yu Koh: Agency for Science, Technology and Research (A*STAR)
Paola Florez Sessions: Agency for Science, Technology and Research (A*STAR)
Woon-Puay Koh: National University of Singapore
Lei Feng: National University of Singapore
Tze Pin Ng: National University of Singapore
Anis Larbi: Agency for Science Technology and Research (A*STAR)
Andrea B. Maier: National University of Singapore
Brian K. Kennedy: National University of Singapore
Niranjan Nagarajan: Agency for Science, Technology and Research (A*STAR)

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome’s role as biomarkers and potential targets for promoting healthy aging.

Date: 2024
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DOI: 10.1038/s41467-024-52097-9

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