A recent paper in Cell proposes a new role for macrophages in the distal colonic mucosa, namely the generation of balloon-like processes (BLPs) that sample luminal contents and protect epithelial cells from the toxic effects of fungal metabolites absorbed during this process. Here Allan Mowat and Calum Bain discuss the implications of these novel findings for intestinal physiology and macrophage biology, highlighting how they extend our understanding of how tissue resident macrophages can adapt precisely to the physiological needs of individual anatomical niches.