Mechanisms by which gut microorganisms influence food sensitivities

Abstract

Finely tuned mechanisms enable the gastrointestinal tract to break down dietary components into nutrients without mounting, in the majority of cases, a dysregulated immune or functional host response. However, adverse reactions to food have been steadily increasing, and evidence suggests that this process is environmental. Adverse food reactions can be divided according to their underlying pathophysiology into food intolerances, when, for instance, there is deficiency of a host enzyme required to digest the food component, and food sensitivities, when immune mechanisms are involved. In this Review, we discuss the clinical and experimental evidence for enteric infections and/or alterations in the gut microbiota in inciting food sensitivity. We focus on mechanisms by which microorganisms might provide direct pro-inflammatory signals to the host promoting breakdown of oral tolerance to food antigens or indirect pathways that involve the metabolism of protein antigens and other dietary components by gut microorganisms. Better understanding of these mechanisms will help in the development of preventive and therapeutic strategies for food sensitivities.

Key points

  • The mechanisms underlying the expression of food sensitivities remain unclear; however, several studies demonstrate that gut microorganisms, along with other host predisposing factors, dictate the development of these conditions.

  • Gut microorganisms can degrade or modify immunogenic food antigens or allergens, increasing or reducing their immunogenicity.

  • Dietary food components that are insufficiently digested by host enzymes become bacterial substrates, leading to the production of metabolites such as short-chain fatty acids, which are involved in gut homeostasis.

  • One key factor in the development of food sensitivities is intestinal barrier dysfunction, which can be influenced by gut microorganisms and pathogens through different pathways.

  • Mucosal dendritic cells present dietary antigens to naive T helper cells, promoting their differentiation into peripheral T regulatory cells; virus–host interactions abrogate this response, inducing a pathogenic response to antigens.

  • Enteric parasites induce T helper 2 cell immunity and protect against food allergy; this contradiction is explained by the observation that parasites induce IL-10, which blocks type 2 immunity.

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Fig. 1: Classification of adverse reaction to food according to underlying pathophysiology.
Fig. 2: Microbial metabolism in the pathogenesis of food sensitivities.
Fig. 3: Microorganisms can promote food sensitivities.

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Acknowledgements

E.F.V. is funded by Canadian Institute of Health Research grant MOP#142773 and holds a Canada Research Chair in Microbiota, Inflammation and Nutrition. A.C. holds a fellowship award from the Farncombe Family. M.M. was awarded a Crohn’s & Colitis Foundation of America Research fellowship award (ID: 480735). B.J. is funded by grants R01DK098435, R01DK100619 and R01DK067180 and by Digestive Diseases Research Core Center grant P30 DK42086. The authors thank R. Hinterleitner for critically editing the Review.

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Nature Reviews Gastroenterology & Hepatology thanks M. D. Kulis, H. Sampson and H. Tlaskalova-Hogenova for their contribution to the peer review of this work.

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Caminero, A., Meisel, M., Jabri, B. et al. Mechanisms by which gut microorganisms influence food sensitivities. Nat Rev Gastroenterol Hepatol 16, 7–18 (2019). https://doi.org/10.1038/s41575-018-0064-z

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