Unlock the science of aging: how gut microbes and plant nutrients collaborate to delay disease and promote a longer, healthier life.
Review: Promotion of healthy aging through the nexus of gut microbiota and dietary phytochemicals. Image Credit: Kateryna Kon / Shutterstock
In a recent study published in the journal Advances in Nutrition, researchers reviewed current knowledge on the benefits of phytochemicals and the role of gut microbiota in influencing human lifespans. They collate findings from almost 200 publications highlighting how interactions between phytochemicals and gut microbes give rise to plant-derived metabolites, such as urolithins, equol, and sulforaphane, which may delay aging and its associated chronic diseases.
The review is divided into three parts – 1. An introduction to human aging and gut microbiota, and the impacts of the latter on the former, 2. The importance of phytochemicals and the mechanisms governing the interactions between these molecules and gut microbiota, and 3. Bioactive metabolites, gut microbes, and the latter’s contribution to healthy aging.
What is aging?
‘Aging’ is the natural process of tissue and cellular function deterioration experienced by all living organisms as they grow old. Advances in modern medicine have substantially extended human lifespans but have unintentionally resulted in a gradually aging population, displaying increased susceptibility to age-associated diseases, including cancers, neurodegeneration, musculoskeletal disorders, cardiovascular diseases (CVDs), and immune system failure.
To address the public health concerns of an increasingly aged society, recent research has focused on ‘healthspan,’ the duration of an individual’s life during which they remain free from age-associated ailments. Research aimed at prolonging human healthspan has identified deregulated nutrient sensing, mitochondrial dysfunction, chronic inflammation, stem cell exhaustion, cellular senescence, and dysbiosis (alterations in gut microbial composition and metabolite-producing performance) as the key hallmarks of aging.
How can we prolong our health span?
Studies on the physiologies of healthy centenarians (persons living for 100 years or more), the gold standard for ideal human aging, suggest that diet and gut microbiota composition and diversity may comprise the most crucial modifiable factors that can help humans stay healthy and disease-free for longer. Gut microbial evaluations of centenarians reveal relative microbial composition patterns similar to those of young adults who are lacking dysbiosis and other hallmarks of aging.
A common revelation in these assessments is that centenarians routinely choose healthy diets rich in plant-based foods, including legumes, vegetables, fruits, nuts, whole grains, and herbs, all known sources of phytochemicals. These plant-derived compounds serve as precursors for beneficial microbial metabolites that support gut barrier integrity and overall gastrointestinal (GI) health. Phytochemicals are plant-derived nonnutritive bioactive compounds that, while previously thought to play minor health roles due to their poor absorptive potential, are increasingly researched for their interplay with gut microbial stability.
Some gut microbes are now known to use certain phytochemicals, such as polyphenols, as raw materials for producing microbial metabolites essential in maintaining gastrointestinal (GI) health and gut barrier integrity. For instance, the gut microbiota can convert ellagitannins from foods like pomegranates into urolithins, which have been linked to anti-inflammatory and antioxidant benefits.
In contrast, excess unhealthy fats and sugary food are usually absent from centenarian diets. Recent evidence highlights the disruptive effects of these dietary items on gut microbial populations and overall intestinal health. Genetics, medication use, and environmental factors also play crucial roles in shaping gut microbial composition and function.
Gut microbiota's role in health and aging
Advances in nutraceutical and gut microbial research aided by the development of next-generation sequencing technologies reveal that the gut microbiome is crucial in maintaining intestinal barrier function, modulating host immunity, maintaining drug and nutrient metabolism, and protecting against invading pathogens. Furthermore, several gut-derived circulatory metabolites have been demonstrated to play key roles in host-microbiota communication (signaling molecules), host immune modulation, and even neurological functioning.
“Various inter-related factors influence the composition and function of the gut microbiota, including host genetics, age, diet, medication, health status, as well as physical activity and social/living environment.”
Aging has been shown to significantly alter the composition of mammalian gut microbial communities – with commensal taxa being gradually replaced by pathobionts. This dysbiosis has been linked to several CVDs, chronic inflammation, neurodegeneration, and certain cancers. However, these changes may be reversible - fecal transplanting experiments in murine models revealed that replacing young mice gut microbiota with those from aged mice can induce age-associated ailments in the former. Conversely, gut microbial transplants from healthy young donors have been observed to ameliorate aging symptoms in aged mice. These findings suggest that gut microbiota manipulation could hold potential for future therapeutic interventions.
Together, these findings may help usher in novel therapeutic interventions that increase human healthspan in the future.
Phytochemicals – direct and indirect influences on healthspan
Food-derived phytochemicals are rapidly rising to the forefront of healthy aging research given their known antioxidant, immune protective, and anti-inflammatory properties. Previously thought to play negligible roles in gut health, recent evidence suggests that phytochemicals (e.g., daidzein, isorhamnetin, and genistein) may serve as signaling molecules, inhibiting nuclear factor kappa B (NF-κB) and promoting nuclear factor erythroid 2-related factor 2 (Nrf2), key modulatory components of pro-inflammatory gene activation and antioxidant defensive systems.
Some phytochemicals are metabolized by gut microbiota, promoting beneficial commensal bacterial communities while suppressing the growth of pathogens (prebiotic function).
“Phytochemicals may exert anti-bacterial, anti-fungal, and anti-viral properties through interacting with microbial proteins, disrupting DNA synthesis and replication, interfering with bacterial cell walls, disrupting biofilms or quorum sensing, and inhibiting energy metabolism.”
In summary
Diet and gut microbiota are increasingly being researched for their influence on human healthspan and their protective effects against age-related diseases. The review highlights how specific microbial metabolites derived from dietary phytochemicals, such as urolithins and equol, may play a crucial role in this process. Simultaneously, phytochemicals are revealed to promote gut health, reduce inflammation, and enhance microbial diversity directly and indirectly (through microbial-host signaling). Together, these lines of research show promise in preventing and treating age-related diseases in the future.
Journal reference:
- Beaver, L. M., Jamieson, P. E., Wong, C. P., Hosseinikia, M., Stevens, J. F., & Ho, E. (2025). Promotion of healthy aging through the nexus of gut microbiota and dietary phytochemicals. Advances in Nutrition, 100376. DOI: 10.1016/j.advnut.2025.100376, https://www.sciencedirect.com/science/article/pii/S2161831325000122