Dietary switch and intermittent fasting ameliorate the disrupted postprandial short-chain fatty acid response in diet-induced obese mice.

Abstract

Intermittent fasting holds promise as a prevention for obesity, but its effects on established obesity remain uncertain. We examined two intermittent fasting regimens in diet-induced obese mice, either maintained on a hypercaloric diet or switched to normal chow diet, and compared their effects with those of dietary switch alone (12 mice/group). We assessed metabolic parameters, gut microbiota composition, and fasting and postprandial short-chain fatty acids (SCFAs) levels. Additionally, faecal microbiota was analysed before and after diet-induced weight loss in 18 individuals with obesity. Intermittent fasting with a hypercaloric diet effectively mitigated weight gain and improved metabolic health-glucose, insulin, total cholesterol, triglycerides, and glucose tolerance (p < 0.05) to an extent comparable with dietary switch. Intermittent fasting increased faecal SCFAs levels, especially postprandially (acetate, propionate, and butyrate, p < 0.05), mirroring dietary switch. Combining intermittent fasting with dietary switch yielded the greatest improvement in glucose tolerance (p < 0.01) and exerted a more pronounced effect on gut microbiota composition (28 significant genera), albeit with reduced SCFA changes. The relative abundance of Alistipes finegoldii was associated with postprandial SCFAs levels and/or metabolic parameters in both mice and humans. Intermittent fasting on a hypercaloric diet protects against obesity, while combining intermittent fasting with dietary switch improves glucose metabolism independently of body weight. Both effects are associated with specific microbiota changes and postprandial SCFA dynamics, highlighting the connection between intermittent fasting, microbiota, and metabolic health. Supported by the Institute of Health "Carlos III", Ministry of Science and Innovation and "La Caixa" Foundation.