Exercise improves gut microbial metabolites in an intensity-dependent manner: a pooled analysis of randomized controlled trials

Abstract

Background: Obesity and the metabolic syndrome (MetS) are global health challenges. The gut microbiome, particularly its fermentation products, short-chain fatty acids (SCFAs), is increasingly recognized as a key modulator of cardiometabolic health. Growing evidence suggests that exercise may play a critical role in SCFA production. This study presents a pooled analysis of data from three randomized controlled trials to examine the effects of low-volume high-intensity (HIGH-EX) versus moderate-intensity (MOD-EX) interval training, each combined with single-set resistance training, on SCFAs and cardiometabolic health in obese MetS patients. Methods: Data from 113 patients allocated to 12 weeks of HIGH-EX, MOD-EX, or a control group (CON) were analyzed. Fecal SCFA concentrations, cardiorespiratory fitness (VO2max), muscle strength, inflammation (hsCRP), and MetS severity (MetS z-score) were assessed pre- and post-intervention. Exercise intensity was monitored via regular blood lactate measurements during interval training. Results: HIGH-EX and MOD-EX improved VO2max (+4.2 and +2.7 mL/kg/min), strength across major muscle groups (+19 to 29%), hsCRP (–2.2 and –1.3 mg/L), and MetS z-score (–1.1 and –0.5 units). Only HIGH-EX significantly increased total fecal SCFAs (+30%), including acetate (+27%), propionate (+28%), and butyrate (+43%). Mean blood lactate concentrations during training were strongly correlated with SCFA increases (r = 0.68, p < 0.001). No changes were observed in CON. Conclusions: Low-volume combined interval and resistance training improved fitness and metabolic health at both moderate and higher intensities. However, only HIGH-EX enhanced SCFA production, potentially associated with lactate-mediated microbial adaptations. Exercise intensity may thus be a key determinant of gut-metabolic benefits.