A research team led by Professor Wong Wing Tak Jack, from the School of Life Sciences at The Chinese University of Hong Kong (CUHK), has made a significant breakthrough in geriatric gut health research. The team’s study reveals that hydroxylated coumarin derivatives, a class of plant-derived phenolic compounds, effectively reshape the gut microbiome environment in ageing mice and regulate metabolic pathways to mitigate ageing-related gut dysbiosis. This pioneering work has been published as a cover article in the leading international journal, Journal of Agricultural and Food Chemistry.

Ageing Population and Gut Dysbiosis: A Pressing Public Health Challenge with Scarce Interventions

With the global ageing population expanding, age-related gastrointestinal disorders and systemic diseases, such as metabolic syndrome and cardiovascular diseases, have become major public health challenges. Age-related gut dysbiosis, characterised by reduced microbial diversity and overgrowth of pathogenic bacteria, is closely linked to oxidative stress and impaired detoxification pathways, forming a vicious cycle of microbial imbalance and host dysfunction. However, effective gut-targeted interventions for the elderly remain limited.

Key Findings: Hydroxylation-Driven Modulation of Gut Microbiota and Metabolism

To address ageing-related issues, Prof. Wong’s research team employ simulated colonic fermentation models, which include aged fecal inocula, integrating antioxidant profiling, short-chain fatty acids (SCFAs) analysis, 16S rRNA sequencing, and untargeted metabolomics, to explore the effects of three naturally occurring coumarin derivatives (coumarin, umbelliferone, and esculetin) with distinct hydroxylation patterns. These experimental approaches avoid the ethical and practical constraints associated with in vivo aged rodent models, thereby enabling precise investigation of the structure-activity relationships among these coumarin compounds.

Notably, our results reveal clear hydroxylation-dependent regulatory effects on gut homeostasis; (1) Esculetin, a di-hydroxylated derivative, exhibits the most comprehensive beneficial efficacy, significantly increasing the production of acetate and propionate while enriching beneficial microbial taxa such as Ileibacterium and Enterococcus; (2) Umbelliferone, a mono-hydroxylated derivative, selectively promotes butyrate synthesis and enriched Bacteroides, a genus associated with gut health; (3) Non-hydroxylated coumarin shows only modest induction of SCFAs; (4) Impressively, all three coumarin derivatives are found to release antioxidant metabolites, a phenomenon that correlates closely with microbiota-mediated detoxification processes in the gut.

“Our study establishes hydroxylated coumarins as promising prebiotics for ageing gut health, providing a clear mechanistic basis for the development of gut-targeted strategies for ageing residents,” said Professor Wong. The findings offer new insights into the interplay between dietary plant compounds, gut microbiota, and host metabolism, paving the way for novel dietary supplements or therapeutic agents to improve geriatric health. Silver economy is one of the focuses of the Hong Kong government now. Thus, we believe that our findings will greatly benefit society and ageing populations, stimulating the economy and improving social living happiness.

For the full research, please visit: https://pubs.acs.org/doi/10.1021/acs.jafc.5c10344