by Agency for Science, Technology and Research (A*STAR), Singapore

Aging-associated shifts in gut microbiome richness and relative abundance of key species. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-52097-9

A new study has revealed that gut bacteria may play a key role in aging, and that specific microbes could be targeted to promote healthy aging.

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The Nature Communications study was conducted by scientists from the Agency for Science, Technology and Research Genome Institute of Singapore (A*STAR GIS), in collaboration with researchers from the A*STAR Singapore Immunology Network (A*STAR SIgN), A*STAR Institute for Human Development and Potential (A*STAR IHDP) and the National University of Singapore (NUS).

Aging is a complex, multi-factorial phenomenon with progressive decline in several physiological functions. As Singapore faces a rapidly growing aging population, researchers are seeking ways to understand the aging process and identify key lifestyle and dietary factors to encourage healthy aging.

As part of this effort, the team conducted the first large-scale study on over 200 octogenarians (people aged 80–89) in Singapore. Their investigation revealed how the gut microbiome changes with age, highlighting key microbial species associated with aging, and their potential effects on health.

Using advanced DNA sequencing, the research team discovered a significant decrease in gut bacterial diversity as individuals age. A particularly noteworthy finding was the decline of Faecalibacterium prausnitzii, a crucial bacterium responsible for producing butyrate—an essential short-chain fatty acid that maintains gut health, reduces inflammation, supports gut barrier function, and facilitates gut-brain communication.

Researchers observed an increase in Alistipes and Bacteroides species, with Alistipes utilizing alternative substrates from Bacteroides to generate butyrate. This notable switch may compensate for the reduction of F. prausnitzii, enhancing the metabolic capacity of the elderly gut to produce butyrate and promoting healthier aging.

The team then turned to preclinical models of healthy aging to validate their findings from the human cohort. Despite differences in the microbes present in different host species, the researchers made a surprising discovery that they had remarkably similar functional enrichments, particularly in pathways related to butyrate production. This indicates that although the specific microbes may differ across species, the functional roles they play in fostering healthy aging may be similar.

Additionally, the research team examined the association between gut bacterial changes and health markers such as inflammation, blood sugar and vitamin levels. They identified Parabacteroides goldsteinii, a promising probiotic species associated with fasting blood glucose levels, as well as key gut species like Streptococcus parasanguinis and Bacteroides coprocola, which were linked to serum Vitamin B12 levels, suggesting that these bacteria may serve as indicators for monitoring healthy aging. Recognizing the potential of these associations, the researchers envisaged the development of non-invasive tests for frailty based on gut bacteria analysis.

In the next phase of their research, the team plans to further investigate the identified microbial strains and their metabolic pathways. By using preclinical testing, they aim to explore how these findings can be potentially translated into formulations that promote healthy aging.

Aarthi Ravikrishnan, the lead scientist of the study from A*STAR GIS, commented, “Our research offers key insights into the unique aspects of the gut microbiome and the metabolic shifts associated with aging. This study opens exciting new avenues for exploring the biology of aging, with a particular focus on populations in Asia.”

Associate Professor Niranjan Nagarajan, Associate Director, Genome Architecture, and Senior Group Leader, Laboratory of Metagenomic Technologies and Microbial Systems at A*STAR GIS, added, “Our findings lay the groundwork for future research aimed at developing targeted probiotic and prebiotic therapies to enable healthy aging through gut microbiome modulation.”

Dr. Wan Yue, Executive Director at A*STAR GIS, commented, “This study has unveiled a better understanding and characterization of the gut microbiome in our local aging population and the potential biomarkers or probiotics unique to the Asian population that can improve healthy aging and to identify individuals at risk for aging-associated diseases. This can serve as a useful marker for early detection of diseases and interventions, improving patient prognosis.”

More information: Aarthi Ravikrishnan et al, Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes, Nature Communications (2024). DOI: 10.1038/s41467-024-52097-9

Journal information:Nature Communications

Provided by Agency for Science, Technology and Research (A*STAR), Singapore

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