November 01, 2014 10:00 pm

histamine intolerance, mast cell activation, IBS, IBD, Alison Vickery, Health, Australia

The histamine intolerance IBS and IBD connection are not well known.

Histamine intolerance is a symptom of a wide variety of diseases.

This blog post looks at irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD, including Crohn’s disease and ulcerative colitis).

IBS, IBD, histamine producing bacteria, histamine intolerance, gut health, alison vickery, health, australia

Irritable Bowel Syndrome (IBS)

IBS is related to a disrupted gut immune response and disrupted intestinal micro-organisms.

People with IBS are known to have more mast cells in just the diseased area than other people. Their mast cells spontaneously secrete higher amounts of histamine, and increased histamine levels are associated with worse symptoms.


Inflammatory Bowel Diseases (IBD)

Crohn’s disease and ulcerative colitis are thought to result from a disrupted interaction between; the gut’s immune system, intestinal micro-organisms, and genetic mutations.

Studies showed that people with IBD have an increased number of mast cells in the gut and an increased rate of histamine secretion, but unlike IBS, they have reduced function of both the DAO and HNMT genes.  DAO once again metabolizes extra-cellular histamine, whereas HNMT metabolizes intra-cellular histamine.


The Immune System

An auto-immune response is usually a tightly regulated process that prevents immune-related diseases.

It consists of a pro-inflammatory response (which initiates an immune reaction to protect the body from an infection) and an anti-inflammatory response (which halts the immune reaction to innocuous environmental antigens).

The immune system is in a chronic pro-inflammatory state in IBS and IBD. It can no longer perform the anti-inflammatory role and instead responds to various innocuous environmental antigens.


histamine intolerance, mast cell activation, microbiome, dysbiosis, alison vickery, health, Australia


Histamine plays a role in the development and severity of IBS and IBD.

It is currently speculated that histamine is directly or indirectly involved in the immune response by inducing tolerance or sensitization to a substance.

Four known histamine receptors (H1, H2, H3, and H4) are currently involved in the immune system.

H1R and H4R are thought to be pro-inflammatory and initiate an immune reaction. H2R and H3R are thought to be anti-inflammatory and halt an immune reaction.

H1R antagonists are commonly used to suppress the short-term pro-inflammatory response.  Long-term use is thought to alter the equilibrium of the immune system. There are currently no H4R antagonists available, although one drug is being used in clinical trials (with the ominous name of JNJ-7777120).

Similarly, some studies show that prolonged use of H2R antagonists may contribute to developing IgE-mediated food allergies. There are currently no H3R antagonists available.

This is an emerging hypothesis that still needs more validation.



The intestinal microbiota composition plays a pathological role in developing IBS and IBD.

At the same time, some bacteria are known to affect the histamine receptor activity and play an anti-inflammatory type protective role. In particular, bifidobacterium infantis 35624 and lactobacillus rhamnosus have been proven to regulate the H2 receptor.

This explains why people with IBD and IBS get relief from their symptoms with these specific bacteria.


Mast cells

Mast cells are also crucial in IBD and IBS, as mast cells accumulate at the visible line of demarcation between normal and abnormal mucosa. It is unknown if the mast cells are causing further damage or limiting the expansion of damage. Ketotifen (a mast cell stabilizer) is proven to reduce IBS symptoms.

Similarly, butyrate, particularly Pure Encapsulations Sun Butyrate, is known to act as a mast cell stabilizer and is helpful for IBS and IBD.


Genetic Mutations

Genetic DAO and HNMT mutations are known to be active in IBD sufferers. 23and Me collects this data, and prometheus reports on these mutations.


histamine intolerance, mast cell activation, autoimmunity, Alison Vickery, Health, Australia


Histamine intolerance is a symptom of many diseases, including IBD and IBS. The similarity of the symptoms requires expert diagnosis and may explain the variations in dietary and treatment experiences.

Current treatment strategies appear to promote H2R expression through targeted probiotics such as bifidobacterium infantis 35624 and Lactobacillus rhamnosus, which is thought to regulate not only the immune system but protect against allergic sensitization and the development of auto-immune disorders.

Ketitofen and a low histamine diet are also effective in reducing symptoms. As is Pure Encapsulations Sun Butyrate.

There is much that is still not known.


Additional Reading

Smolinska S, Jutel M, Crameri R, O’Mahony L. Histamine and gut mucosal immune regulation. Allergy 2013; DOI: 10.1111/all.12330.