Many people in Asia can expect to live longer, but will they do so in good health? With over a third of the region’s population expected to be 60 years or older by 2050, there’s an increasing urgency to understand the complex factors that shape healthy ageing.
A key player might be our gut microbiomes. As we age, those tiny communities of bacterial and fungal species can shift in surprisingly consistent patterns linked to age-related diseases and frailty. However, to date, most studies in this area have captured a relatively low-resolution view of these connections, notes Aarthi Ravikrishnan, a Scientist at the A*STAR Genome Institute of Singapore (A*STAR GIS).
“Older genomic methods, such as 16s rRNA sequencing, only detect microbes that match specific genes,” Ravikrishnan explained. “It’s like assessing the variety of mixed Lego bricks by focusing on the most common colours.”
To dive deeper, recent studies have turned to shotgun metagenomics, a next-generation DNA sequencing technique that breaks up all the genetic material present in a sample, then randomly sequences them, increasing the odds of catching rare species.
“Shotgun metagenomics is a powerful tool for studying the full diversity of complex microbial communities in detail,” added Indrik Wijaya, an A*STAR GIS Bioinformatics Specialist.
Yet these studies have been limited by small cohort sizes, making it difficult to account for confounding factors like diet, medication and lifestyle. To get a clearer view, Ravikrishnan and Wijaya worked with colleagues from A*STAR GIS including Niranjan Nagarajan, Associate Director and Senior Director; the A*STAR Singapore Immunology Network (A*STAR SIgN); the A*STAR Institute for Human Development and Potential (A*STAR IHDP); and the Yong Loo Lin School of Medicine, National University of Singapore, to apply shotgun metagenomics on a large cohort from SG90: a decades-long population study of community-dwelling elderly persons in Singapore.
“[SG90] provided a rich health dataset which helped us effectively control for those confounding factors in our models,” said Ravikrishnan.
With metagenomic data on the microbiomes of over 200 SG90 participants, the team integrated data from younger Singaporean and Asian cohorts into statistical models, looking for age-related patterns.
“One thing that stood out was the age-related decline of Faecalibacterium prausnitzii, a key butyrate-producing bacterium. Butyrate maintains gut health by reducing inflammation, supporting gut barrier integrity and facilitating gut-brain communication,” said the researchers. “Intriguingly, F. prausnitzii’s decline came with the rise of Alistipes and Bacteroides species that teamed up to become major butyrate producers, potentially taking over F. prausnitzii’s role in gut health. We saw these functional enrichments repeated in mouse models of healthy ageing, suggesting they may play similar roles in promoting that state.”
The team also found microbial associations with clinical biomarkers, such as fasting blood glucose, which could support non-invasive tests and interventions for healthy ageing trajectories.
Moving forward, the team plans to isolate and characterise key microbial strains linked with healthy ageing from their study, as well as assess their effectiveness as supplements for reducing frailty. “We believe these experiments will provide critical insights and facilitate the translation of our findings into practical applications for improving healthy ageing,” they concluded.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Genome Institute of Singapore (A*STAR GIS), A*STAR Singapore Immunology Network (A*STAR SIgN) and A*STAR Institute for Human Development and Potential (A*STAR IHDP).
