Histamine Metabolism in IBD: Towards Precision Nutrition

Abstract

Patients with Inflammatory Bowel Disease (IBD) exhibit a dysregulated immune response that may be further exacerbated by bioactive compounds, such as histamine. Current dietary guidelines for IBD primarily focus on symptom management and flare-up prevention, yet targeted nutritional strategies addressing histamine metabolism remain largely unexplored. This narrative review aims to summarize the existing literature on the complex interplay between IBD and histamine metabolism and propose a novel dietary framework for managing IBD progression in patients with histamine intolerance (HIT). Relevant studies were identified through a comprehensive literature search of PubMed/MEDLINE, Google Scholar, ScienceDirect, Scopus, and Web of Science. The proposed low-histamine diet (LHD) aims to reduce the overall histamine burden in the body through two primary strategies: (1) minimizing exogenous intake by limiting high-histamine and histamine-releasing foods and (2) reducing endogenous histamine production by modulating gut microbiota composition, specifically targeting histamine-producing bacteria. In parallel, identifying individuals who are histamine-intolerant and understanding the role of histamine-degrading enzymes, such as diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT), are emerging as important areas of focus. Despite growing interest in the role of histamine and mast cell activation in gut inflammation, no clinical trials have investigated the effects of a low-histamine diet in IBD populations. Therefore, future research should prioritize the implementation of LHD interventions in IBD patients to evaluate their generalizability and clinical applicability.

Keywords: Crohn’s disease; DAO; IBD; histamine; histamine intolerance; histamine-producing bacteria; low-histamine diet; mast cell activation; nutrition; ulcerative colitis.

Figure 1

Histamine’s endogenous and exogenous sources, synthesis, and degradation enzymes intra- and extracellularly. Abbreviations: diamine oxidase (DAO); histamine-N-methyltransferase (HNMT).

Figure 2

Histamine-producing bacteria’s metabolism and gut epithelial diffusion. Abbreviations: histidine decarboxylase (HDC).