Regional Diets Targeting Gut Microbial Dynamics to Support Prolonged Healthspan

Abstract

In the last 150 years, we have seen a significant increase in average life expectancy, associated with a shift from infectious to non-communicable diseases. The rising incidence of these diseases, for which age is often the largest risk factor, highlights the need for contemporary societies to improve healthy ageing for their growing silver generations. As ageing is an inevitable, non-reversing and highly individualised process, we need to better understand how non-genetic factors like diet choices and commensal gut microbes can modulate the biology of ageing. In this review, we discuss how geographical and ethnic variations influence habitual dietary patterns, nutrient structure, and gut microbial profiles with potential impact on the human healthspan. Several gut microbial genera have been associated with healthy elderly populations but are highly variable across populations. It seems unlikely that a universal pro-longevity gut microbiome exists. Rather, the optimal microbiome appears to be conditional on the microbial functionality acting on regional- and ethnicity-specific trends driven by cultural food context. We also highlight dietary and microbial factors that have been observed to elicit individual and clustered biological responses. Finally, we identify next generation avenues to modify otherwise fixed host functions and the individual ageing trajectory by manipulating the malleable gut microbiome with regionally adapted, personalised food intervention regimens targeted at prolonging human healthspan.

Keywords: bioactive compounds; gut microbiome; gut microbiota; healthy ageing; personalised diet; phytonutrients; prolonged healthspan.

FIGURE 1

An individual’s healthspan is determined by inter-organ crosstalk of genetic, and modifiable environmental and lifestyle events that may be illustrated as a characteristic fingerprint, which influences body physiology, metabolism, and excretion.

FIGURE 2

Life-long accumulation of damage to body functions and organ systems leads to a discrepancy between chronological and biological ageing. Further, these individual nodes and inter-organ crosstalk may contribute to variability of an individual’s ageing process.

FIGURE 3

The holobiont genome comprise of the human host genome (fixed at conception with limited accumulation of somatic mutations throughout life) and dynamic microbiome (amenable to change following dietary variations). Dietary intake and habits of the human host can determine the genomic configuration and transcriptional activity of the commensal gut microbiota that break down ingested foods to produce bioactive metabolites with a wide range of effects on the human host. Illustration was created with BioRender.com.

FIGURE 4

Centenarians harbour distinct gut microbial species and community structures unique to the region, suggesting that microbial functional and biochemical properties are pivotal to healthy ageing, rather than the phylogenetic composition. Data adapted from Claesson et al. (2012), Fang et al. (2015), Biagi et al. (2016), Kong et al. (2016), Bian et al. (2017); Bong-Soo et al. (2019), Naito et al. (2019), Salazar et al. (2019), Tuikhar et al. (2019), Wu et al. (2019), and Luan et al. (2020).

FIGURE 5

An illustration of how physiology (individualised ageing profile) and host-microbiome synergy may characterise an individual approaching their twilight. Introducing regionally adapted, personalised dietary intervention to select for or nurture the malleable gut microbiome may alter the ageing trajectory to compensate for age-related loss of physiological functionality.