Fasting and re-feeding independently alter mouse gut microbiota during intermittent fasting

Intermittent fasting (IF) elicits metabolic benefits that are partially driven by the gut microbiome. Studies have focused on endpoint IF-induced changes in the gut microbiome but have not explored whether the oscillating nature of IF elicits day-to-day microbiome changes that could independently affect health. To discriminate the long-term and short-term effects of IF on the gut microbiota, we fasted mice every other day (IF1:1) or every two days (IF1:2), measuring daily changes in body mass and composition, food intake, and gut microbiota composition. We show that short-term effects of fasting and re-feeding on gut microbiota composition outweigh longer-term effects of IF treatment, with composition responding differently to re-feeding and fasting. Re-feeding specifically promoted rapid expansion of Lactobacillus, a bacterial genus linked mechanistically to the metabolic benefits of IF. Our results highlight the plasticity of the gut microbiota, especially re-feeding effects, as a potential contributor to microbiome-mediated metabolic benefits of IF.