Promotion of Healthy Aging Through the Nexus of Gut Microbiota and Dietary Phytochemicals

Abstract

Aging is associated with the decline of tissue and cellular functions, which can promote the development of age-related diseases like cancer, cardiovascular disease, neurodegeneration, and disorders of the musculoskeletal and immune systems. Healthspan is the length of time an individual is in good health and free from chronic diseases and disabilities associated with aging. Two modifiable factors that can influence healthspan, promote healthy aging, and prevent the development of age-related diseases, are diet and microbiota in the gastrointestinal tract (gut microbiota). This review will discuss how dietary phytochemicals and gut microbiota can work in concert to promote a healthy gut and healthy aging. First, an overview is provided of how the gut microbiota influences healthy aging through its impact on gut barrier integrity, immune function, mitochondria function, and oxidative stress. Next, the mechanisms by which phytochemicals effect gut health, inflammation, and nurture a diverse and healthy microbial composition are discussed. Lastly, we discuss how the gut microbiota can directly influence health by producing bioactive metabolites from phytochemicals in food like urolithin A, equol, hesperetin, and sulforaphane. These and other phytochemical-derived microbial metabolites that may promote healthspan are discussed. Importantly, an individual's capacity to produce health-promoting microbial metabolites from cruciferous vegetables, berries, nuts, citrus, and soy products will be dependent on the specific bacteria present in the individual's gut.

Keywords: diet; dysbiosis; gut health; gut microbiome; healthspan; lifespan; microbial metabolite; phytochemicals.

FIGURE 1

Aging is typically associated with cellular and tissue level dysfunction that adversely affects healthspan and lifespan and promotes the development of cancer, osteoporosis, sarcopenia, neurodegeneration, and cardiovascular and metabolic diseases. Consuming foods or supplements with phytochemicals can promote a healthy gastrointestinal tract, which in turn can promote healthy aging. Additionally some bacteria in the gut can produce metabolites that act locally (e.g. improve intestinal barrier function) or are absorbed and act in distant tissues (e.g. brain and muscle) to improve healthspan. Created in BioRender. BioRender.com/a48l667.

FIGURE 2

The interplay between age-related dysbiosis, intestinal permeability, and other hallmarks of aging that results in local and systemic inflammation. Dysbiosis contributes to increased intestinal permeability, altered microbial metabolite production, and release of microbial products and endotoxin into circulation that contributes to systemic inflammation. At the same time, mitochondrial dysfunction, cellular senescence, and inflammaging trigger local inflammatory response that further drives dysbiosis. Systemic chronic inflammation in turn further amplifies dysbiosis and age-related dysfunction that contributes to neuroinflammation and age-related diseases. Created in BioRender. BioRender.com/y74r211. mtDNA, mitochondrial DNA; ROS, reactive oxygen species; SASP, senescence-associated secretory phenotype.

FIGURE 3

Phytochemicals’ multifaceted effects on an aging gut environment with intestinal permeability and chronic inflammation. Many phytochemicals have direct anti-inflammatory effects by targeting cellular signaling pathways. Phytochemicals can also promote intestinal homeostasis by modulating microbial composition, improving function of the gut microbiota by producing microbial metabolites, like SCFAs. Phytochemicals can also be metabolized by gut microbiota into more potent compounds, which act directly on the intestinal mucosa and in some cases are absorbed and enter circulation. Created in BioRender. https://BioRender.com/j57f597. SCFA, short-chain fatty acids.