The role of the microbiota in sedentary lifestyle disorders and ageing: lessons from the animal kingdom

A paradox of so-called developed countries is that, as the major historical causes of human mortality are eliminated or mitigated by medical progress, lifestyle-related diseases have become major killers. Furthermore, as lifespan is extended by the combined effects of modern medicine, health span is struggling to keep apace because of the burden of noncommunicable diseases linked to diet and sedentary lifestyle. The gut microbiome is now recognized as a plastic environmental risk factor for many of these diseases, the microbiome being defined as the complex community of co-evolved commensal microbes that breaks down components of a complex diet, modulates innate immunity, and produces signalling molecules and metabolites that can impact on diverse regulatory systems in mammals. Aspects of the so-called ‘Western’ lifestyle linked to disease risk such as energy dense diet and antibiotic treatment are known to affect the composition and function of the microbiome. Here, we review the detailed mechanisms whereby the gut microbiome may modulate risk of diseases linked to sedentary lifestyle and ageing-related health loss. We focus on the comparative value of natural animal models such as hibernation for studying metabolic regulation and the challenge of extrapolating from animal models to processes that occur in human ageing.