Intermittent Fasting Reduces Obesity-driven Oxidative Stress in the Male Mouse Colon via Changes in Gut Microbiota

BACKGROUND & AIMS: Obesity impairs colon homeostasis by increasing oxidative stress, which is associated with damage to the epithelial barrier and the development of intestinal diseases. Intermittent fasting (IF) improves mitochondrial activity (MA) in metabolic tissues and positively modifies gut microbiota composition, suggesting that this intervention may exert beneficial effects on colon homeostasis. The aim of this study was to evaluate the effect of IF on MA in the colon and its modulation by gut microbiota in a diet-induced obesity mouse model. METHODS: C57BL/6 male mice were fed a control diet or high-fat/high-sucrose diet (HFSD) for 12 weeks, followed by 4 weeks of IF intervention or continued HFSD, with or without antibiotic (AB) treatment. We evaluated MA in colonic mitochondria determined by the oxygen consumption rate and reactive oxygen species (ROS) production, together with gut microbiota composition and metabolome from feces. RESULTS: Mice who underwent IF intervention had a significant decrease in colonic mitochondria oxygen consumption rate and ROS compared with the HFSD group, parameters that were sharply increased by AB administration. Moreover, IF improved colon morphology and epithelial barrier integrity via changes in gut microbiota composition and the metabolome profile, an effect that was modulated by mitochondrial activity and ROS production and not preserved upon AB administration. CONCLUSIONS: We conclude that IF reduces MA in the colon via changes in bacterial taxonomy and metabolites abundance to decrease oxidative stress caused by obesity, establishing a close connection between host MA and gut microbiota.