The Limits of Lifestyle in Metabolic Disease: How the Microbiome Shapes Exercise Response

There is now overwhelming evidence that structured physical exercise exerts broad and durable benefits on human health, with demonstrable population-level effects on metabolic comorbidities, glycaemic control, and all-cause mortality.1–3 However, these positive effects are not uniformly distributed. Inter-individual variability in metabolic response to exercise is substantial, with reported rates of non-response ranging from 7% to 69%.4–6 The liver is no exception to this heterogeneity. Exercise confers clear weight-independent benefits in metabolic dysfunction-associated steatohepatitis (MASH), with multiple intervention studies demonstrating improvements in liver fat fraction and fibroinflammatory burden.