Distinct gut bacteria identified in octogenarians linked to aging and health

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Sep 11 2024

Research uncovers unique gut bacteria in Singaporean seniors, revealing how the microbiome could hold the key to healthier aging

In a recent study published in Nature Communications, researchers investigated gut microbiome function in aging using deep shotgun metagenomic sequences of elderly Singaporeans.

Background

The rising prevalence of chronic aging-related disorders in Asia is attributable to fast demographic shifts. The absence of high-quality in vivo data makes it difficult to grasp the complicated roles of gut microbial variables in healthy aging. There is a need to find lifestyle, nutritional, and pharmacological therapies for healthy aging among Asian cultures.

Studies have discovered links between gut microbiota and age, with various gender- and age-related trajectories. Healthy aging and frailty indices are associated with gut microbiota status, and compositional diversity may be a biomarker for healthy aging. Cohort size and age range hamper attempts to define the gut microbiome in older individuals using shotgun metagenomics.

About the study

In the present study, researchers studied species-level gut microbiome alterations as a function of age in Singapore's community-living octogenarians.

Study datasets included SG90 (234 individuals aged 77 to 97 years), SPMP (109 individuals aged 53 to 74 years), type 2 diabetes study (171 individuals aged 21 to 70 years old), and CPE (82 individuals aged 21 to 80 years). Participants provided blood samples to assess fasting blood glucose, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, high-sensitivity C-reactive protein (hs-CRP), aspartate aminotransferase (AST), alanine transaminase (ALT), and Vitamin B₁₂ levels.

Their stool samples underwent shotgun metagenomic sequencing to reveal high-resolution species-level taxonomic profiles. Researchers corrected these profiles for batch effects using age group as a covariate. They extracted deoxyribonucleic acid (DNA) from the stool samples for enrichment polymerase chain reaction (PCR).

Researchers performed joint species-level analysis and quantified gene expression and pathway abundances. Metabolic pathway analysis indicated the four major pathways for butyrate production. The team also undertook functional and microbial diversity analyses. They associated intestinal microbiota with primary markers for cardiometabolic health, liver health, and inflammation to identify additional gut microbial functions related to healthy aging.

Researchers supplemented C57BL6/J mice with 4% calcium alpha-ketoglutarate (AKG) and analyzed their fecal shotgun metagenomic sequences after three months. Metabolic network analysis yielded metabolic support index (MSI) values for the species identified concerning gut microbes. The HMP Unified Metabolic Analysis Network (HUMAnN2) determined the relative abundance of microbial pathways in gut metagenomes using the Kyoto Encyclopedia of Genes and Genomes (KEGG) as a reference.

Generalized linear models (GLM) and logistic regressions with permutational multivariate analysis of variance (PERMANOVA) identified gut microbes associated with age and clinical phenotypes. To assess the reproducibility of the study findings, researchers identified microbial associations across six additional cohorts of Western and Asian origin. They normalized data using cumulative sum scaling (CSS), total sum scaling (TSS), and association analysis techniques.

Results

There were specific age-related shifts in the gut microbiome characterized by reduced microbial richness, Firmicutes, and Parasutterella counts. In contrast, aging enriched beta diversity in the gut, Acidaminococcaceae genus, Bacteroides xylanisolvens, and Alistipes shahii. These changes indicate potential metabolic expansion in aged individuals towards pathways using amino acids such as L-lysine as precursors relative to the pyruvate-to-butyrate production pathway. Advanced age reduced Roseburia inulinivorans and Faecalibacterium prausnitzii, microbes crucial to butyrate production.

Extending these discoveries to major clinical parameters revealed more than ten robust relationships with inflammatory, cardiometabolic, and hepatic function. These included pathobionts like Klebsiella pneumoniae and potential probiotics like Parabacteroides goldsteinii. The findings emphasize the microbiome's importance as an indicator of healthy aging.

Sugar metabolism pathways are more developed in younger people, whereas mono-, di-, and polysaccharide breakdown is more developed among elders. Microbial glycolytic pathways for simple sugar metabolism are more prevalent in healthy people over 90. Younger people tend to have more microbial lipid metabolism pathways, whereas elders have more amino acid metabolism pathways.

Dietary AKG supplementation in elderly mice enhanced longevity, alleviated inflammation, and decreased frailty indicators. Shotgun metagenomic sequences in stool samples of AKG-supplemented mice revealed a comparable growth in butyrate synthesis pathways in healthy aged mice. The pathways involved in converting lysine to butyrate showed the highest enrichment. Elevated hs-CRP levels relate to Escherichia coli and Streptococcus species, both connected with rheumatoid arthritis, which often develops in middle life.

Conclusion

The study showed a change in microbial richness and functional guilds related to aging, namely in the gut of old Asians. Bacteroides species were the most significant contributors. The researchers discovered strong species-level correlations between gut microbes, clinical markers, and aging-related symptoms. Species richness dropped with age, although beta diversity rose in extreme age ranges.

The diversity in richness and uniqueness trends between cohorts demands more investigation using consistent datasets and, maybe, long-read sequencing. The relationships discovered can be used as biomarkers for healthy aging and identifying those at risk for age-related disorders.