Leveraging diet to engineer the gut microbiome

Autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, have distinct clinical presentations but share underlying patterns of gut microbiome

perturbation and intestinal barrier dysfunction. Their potentially common microbial drivers advocate for treatment strategies aimed at restoring appropriate microbiome function, but

individual variation in host factors makes a uniform approach unlikely. In this Perspective, we consolidate knowledge on diet–microbiome interactions in local inflammation, gut microbiota

imbalance and host immune dysregulation. By understanding and incorporating the effects of individual dietary components on microbial metabolic output and host physiology, we examine the

potential for diet-based therapies for autoimmune disease prevention and treatment. We also discuss tools targeting the gut microbiome, such as faecal microbiota transplantation, probiotics

and orthogonal niche engineering, which could be optimized using custom dietary interventions. These approaches highlight paths towards leveraging diet for precise engineering of the gut

microbiome at a time of increasing autoimmune disease.

This work was supported by the following grants in the laboratory of M.S.D.: Luxembourg National Research Fund (FNR) CORE grants (C15/BM/10318186 and C18/BM/12585940) to M.S.D.; M.B. was

supported by a European Commission Horizon 2020 Marie Skłodowska-Curie Actions individual fellowship (897408); M.W. was supported by a Fulbright grant for Visiting Scholars from the

Commission for Educational Exchange between the United States of America, Belgium and Luxembourg; E.T.G. was supported by the Luxembourg National Research Fund PRIDE (17/11823097) and the

Fondation du Pélican de Mie et Pierre Hippert-Faber, under the aegis of the Fondation de Luxembourg. G.V.P. was supported by a fellowship from the W. Garfield Weston Foundation and E.C.M.

acknowledges the financial support from National Institutes of Health (DK118024).

These authors contributed equally: Mathis Wolter, Erica T. Grant.

Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg

Mathis Wolter, Erica T. Grant, Marie Boudaud, Alex Steimle & Mahesh S. Desai

Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg

Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark

All authors have contributed to the writing and editing of the manuscript.

Nature Reviews Gastroenterology & Hepatology thanks R. Carmody and the other, anonymous, reviewers for their contribution to the peer review of this work.

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