 Antibiotic induced microbiome depletion is one of the most common approaches to modulate the gut microbiome. Here the authors demonstrate that it affects gut homeostasis and glucose metabolism by decreasing luminal short chain fatty acids and leading to a shift of energy utilisation by colonocytes. This article was authored by Amir Zirinpa, Amandine Che, Jeng Jing Zhechu, and others.