Unique Gut Bacteria Found in Singapore Seniors

Researchers used deep shotgun metagenomic sequences of Singapore seniors to analyze the function of the gut microbiome in aging, a study that was just published in Nature Communications.

Context
Rapid demographic changes in Asia are the cause of the increased prevalence of chronic aging-related illnesses in that region. It is challenging to understand the intricate roles of gut microbial factors in healthy aging due to the lack of high-quality in vivo data. Asian cultures need to identify pharmaceutical, dietary, and lifestyle therapies for good aging.

Research has shown that gut microbiota and age are correlated, with different trajectories associated with age and gender. Gut microbiota status is linked to frailty indices and healthy aging, and compositional diversity may be a biomarker for both. Attempts to use shotgun metagenomics to identify the gut microbiome in older adults are hampered by the cohort size and age range.

About the Study

In the current study, scientists examined how age affects species-level gut microbiome changes in Singapore’s community-dwelling octogenarians.

The type 2 diabetes study (171 participants aged 21 to 70 years old), SG90 (234 participants aged 77 to 97 years), SPMP (109 participants aged 53 to 74 years), and CPE (82 participants aged 21 to 80 years) were among the study datasets. In order to measure the levels of aspartate aminotransferase (AST), alanine transaminase (ALT), vitamin B12, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, and high-sensitivity C-reactive protein (hs-CRP), the participants gave blood samples.

Shotgun metagenomic sequencing of their feces samples produced high-resolution species-level taxonomic profiles. Researchers used age group as a covariate to adjust these profiles for batch effects. For the enrichment polymerase chain reaction (PCR), they separated the deoxyribonucleic acid (DNA) from the stool samples.

Researchers measured pathway abundances and gene expression at the combined species-level. The four main routes for the synthesis of butyrate were identified via metabolic pathway analysis. Additionally, the group conducted assessments of microbiological and functional diversity. They associated intestinal microbiota with primary markers for cardiometabolic health, liver health, and inflammation to identify additional gut microbial functions related to healthy aging.

After giving C57BL6/J mice 4% calcium alpha-ketoglutarate (AKG) as a supplement, researchers examined the fecal shotgun metagenomic sequences of the mice three months later. Metabolic support index (MSI) values were obtained for the gut bacteria species by metabolic network analysis. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) as a guide, the HMP Unified Metabolic Analysis Network (HUMAnN2) ascertained the relative abundance of microbial pathways in gut metagenomes.

Gut microorganisms were linked to age and clinical characteristics using generalized linear models (GLM) and logistic regressions with permutational multivariate analysis of variance (PERMANOVA). Six further cohorts of Western and Asian descent were examined for microbiological correlations in order to evaluate the repeatability of the study findings. They used association analysis, total sum scaling (TSS), and cumulative sum scaling (CSS) to normalize the data.

In summary
The study, which focused on the guts of elderly Asians, revealed alterations in microbial richness and functional guilds associated with aging. The majority of the main donors were Bacteroides species. Strong species-level relationships between gut microorganisms, clinical indicators, and symptoms associated with aging were found by the researchers. While beta diversity increased in the outer reaches of the age range, species richness decreased with age.

Further research utilizing consistent datasets and possibly long-read sequencing is necessary due to the variation in richness and uniqueness trends throughout cohorts. The correlations found can serve as biomarkers for both identifying people at risk for age-related illnesses and for healthy aging.

For more information: Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes, Nature Communications, https://doi.org/10.1038/s41467-024-52097-9