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  • Review Article
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Neutrophils: from IBD to the gut microbiota

Nature Reviews Gastroenterology & Hepatology volume 21, pages 184–197 (2024)Cite this article

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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.

Key points

  • The study of neutrophils in inflammatory bowel disease (IBD) has revealed unexpected complexities, with heterogeneous populations and dual functions, both deleterious and protective, for the host.

  • Strong evidence supports an association between defects in neutrophil functions, alterations of the gut microbiota and intestinal inflammation.

  • Neutrophils influence microbiota composition and function, especially in inflammatory conditions.

  • The intestinal microbiota regulates neutrophil production and function, from activation to maturation.

  • Several microbiota-derived metabolites have been identified as modulators of neutrophil activity.

  • It is crucial to elucidate the roles played by neutrophils in host–microbiota interactions to develop new ways to tackle complex diseases associated with microbiota alterations, such as IBD.

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Fig. 1: The role of neutrophils in the development of an IBD-like phenotype.
Fig. 2: Expression levels of IBD susceptibility genes in immune cells.
Fig. 3: Overview of the dialogue between neutrophils and the microbiota.

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Author notes

  1. Jurate Skerniskyte

    Present address: Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania

Authors and Affiliations

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

    Camille Danne & Harry Sokol

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

    Camille Danne & Harry Sokol

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

    Jurate Skerniskyte & Benoit Marteyn

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

    Benoit Marteyn

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

    Benoit Marteyn

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

    Harry Sokol

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H.S. reports lecture fees, board membership or consultancy from Amgen, Fresenius, IPSEN, Actial, Astellas, Danone, THAC, Biose, BiomX, Eligo, Immusmol, Adare, Nestlé, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, AbbVie, has stocks from Enterome Bioscience and is co-founder of Exeliom Biosciences. The other authors declare no competing interests.

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Danne, C., Skerniskyte, J., Marteyn, B. et al. Neutrophils: from IBD to the gut microbiota. Nat Rev Gastroenterol Hepatol 21, 184–197 (2024). https://doi.org/10.1038/s41575-023-00871-3

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