Gut Microbiota, Macrophages and Diet: An Intriguing New Triangle in Intestinal Fibrosis

Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD) without specific treatment. As macrophages are the key actors in inflammatory responses and the wound healing process, they have been extensively studied in chronic diseases these past decades. By their exceptional ability to integrate diverse stimuli in their surrounding environment, macrophages display a multitude of phenotypes to underpin a broad spectrum of functions, from the initiation to the resolution of inflammation following injury. The hypothesis that distinct macrophage subtypes could be involved in fibrogenesis and wound healing is emerging and could open up new therapeutic perspectives in the treatment of intestinal fibrosis. Gut microbiota and diet are two key factors capable of modifying intestinal macrophage profiles, shaping their specific function. Defects in macrophage polarisation, inadequate dietary habits, and alteration of microbiota composition may contribute to the development of intestinal fibrosis. In this review, we describe the intriguing triangle between intestinal macrophages, diet, and gut microbiota in homeostasis and how the perturbation of this discreet balance may lead to a pro-fibrotic environment and influence fibrogenesis in the gut.