Nat Rev Gastroenterol Hepatol. 2023 Dec 18. doi: 10.1038/s41575-023-00871-3.Online ahead of print.

Camille Danne ^1 2, Jurate Skerniskyte ^3 4, Benoit Marteyn ^3 5 6, Harry Sokol ^7 8 9

Author information

¹Sorbonne Université, INSERM UMRS-938, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint-Antoine, Service de Gastroentérologie, Paris, France. camille.danne@inserm.fr.

²Paris Center For Microbiome Medicine (PaCeMM) FHU, Paris, France. camille.danne@inserm.fr.

³CNRS, UPR 9002, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire, Architecture et Réactivité de l'ARN, Strasbourg, France.

⁴Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.

⁵University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg, France.

⁶Institut Pasteur, Université de Paris, Inserm 1225 Unité de Pathogenèse des Infections Vasculaires, Paris, France.

⁷Sorbonne Université, INSERM UMRS-938, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint-Antoine, Service de Gastroentérologie, Paris, France.

⁸Paris Center For Microbiome Medicine (PaCeMM) FHU, Paris, France.

⁹Université Paris-Saclay, INRAe, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that results from dysfunction in innate and/or adaptive immune responses. Impaired innate immunity, which leads to lack of control of an altered intestinal microbiota and to activation of the adaptive immune system, promotes a secondary inflammatory response that is responsible for tissue damage. Neutrophils are key players in innate immunity in IBD, but their roles have been neglected compared with those of other immune cells. The latest studies on neutrophils in IBD have revealed unexpected complexities, with heterogeneous populations and dual functions, both deleterious and protective, for the host. In parallel, interconnections between disease development, intestinal microbiota and neutrophils have been highlighted. Numerous IBD susceptibility genes (such as NOD2, NCF4, LRRK2, CARD9) are involved in neutrophil functions related to defence against microorganisms. Moreover, severe monogenic diseases involving dysfunctional neutrophils, including chronic granulomatous disease, are characterized by intestinal inflammation that mimics IBD and by alterations in the intestinal microbiota. This observation demonstrates the dialogue between neutrophils, gut inflammation and the microbiota. Neutrophils affect microbiota composition and function in several ways. In return, microbial factors, including metabolites, regulate neutrophil production and function directly and indirectly. It is crucial to further investigate the diverse roles played by neutrophils in host-microbiota interactions, both at steady state and in inflammatory conditions, to develop new IBD therapies. In this Review, we discuss the roles of neutrophils in IBD, in light of emerging evidence proving strong interconnections between neutrophils and the gut microbiota, especially in an inflammatory context.