The research article by Sander and colleagues¹ in this issue of Gut, reports their results for expression of histamine receptor subtypes in the human intestinal tract from normal individuals and patients with symptoms of the irritable bowel syndrome (IBS) and/or food allergies (see page 498). Work of this nature was overdue because most of the available histological and functional data for histamine receptors in the small and large intestine were obtained from animal models. The authors’ principal findings for the human bowel are in general agreement with the animal literature that reports on expression of the histamine H₁, H₂, and H₄ receptor subtypes in the enteric nervous system (ENS), intestinal musculature, mucosal epithelium, and immune/inflammatory cells. In contrast, the finding by Sander and colleagues¹ that histamine H₃ receptors are not expressed in the human bowel was unexpected in view of the clearcut evidence for functional involvement of the H₃ receptor subtype in the nervous control of motility, secretion, and blood flow in guinea pig intestine, which serves as the primary animal model.^2–5

The authors’ evidence for altered expression of histamine H₁ and H₂ receptor subtypes in mucosal biopsies from the terminal ileum and large intestine of patients with symptoms of food allergy and/or IBS is consistent with current concepts for the involvement of histamine release from enteric mast cells and its paracrine signalling function in the ENS as an underlying factor in these two disorders.^5–8 Histamine is not expressed by enteric neurones and is not a neurotransmitter in …