Histamine Intolerance & Gut Health

Recent research shows a clear connection between histamine intolerance (HIT) and the gut microbiome. In this article, we examine how histamine affects the intestinal lining, how a “leaky gut” can worsen histamine intolerance, and which specific microbes are involved in HIT.

This is Part 2 of the Histamine series. Also read Part 1: Histamine Intolerance and Part 3: Histamine and Irritable Bowel Syndrome (IBS) to gain a deeper understanding of histamine and histamine intolerance.

What Do We Know Today?

As described in the previous article on histamine intolerance, histamine is a signaling molecule with a wide range of effects throughout the body. White blood cells (such as mast cells and basophils) as well as certain microbes produce histamine. Histamine is found at relatively high levels in the gastrointestinal tract, especially during inflammatory responses. Low levels of the histamine-degrading enzyme DAO are a common cause of elevated histamine levels in the body, leading to symptoms of histamine intolerance (HIT).

The Effect of Histamine on the Intestinal Lining

The body’s mucosal surfaces are constantly exposed to food, microorganisms, and inhaled particles and act as a protective barrier against the outside world. At the same time, these surfaces are home to the microbiome and play an important role in host health, particularly immune function.

In the gut, the mucosal lining protects the intestinal wall from unwanted particles. If this lining is damaged and food particles come into direct contact with the intestinal wall, irritation and immune activation occur. This causes mast cells to release histamine as a protective response, which over time can lead to high histamine levels in the body. In addition, the DAO enzyme is continuously produced and released in the intestinal lining, ensuring the breakdown of histamine.

Dysbiosis—an imbalance between beneficial and harmful gut bacteria—can cause inflammation of the mucosa and damage DAO-producing cells. This results in reduced DAO levels and activity, leading to impaired histamine breakdown. The resulting increase in histamine levels contributes to HIT symptoms.

“Leaky Gut” and Histamine Release

The intestinal barrier allows beneficial substances such as vitamins and minerals to enter the body while keeping harmful substances—such as toxins, pathogens, and large food particles—out. Several protective layers ensure this, including a tightly packed layer of epithelial cells. When this barrier becomes compromised, unwanted particles can leak into the bloodstream, a condition known as “leaky gut.”

These abnormal particles are recognized by the immune system as a threat, triggering inflammation and the release of histamine. In the case of leaky gut, this inflammation becomes chronic, leading to persistently elevated histamine levels and HIT symptoms.

The Link Between the Gut and HIT

An altered gut microbiome is now recognized as an important factor in histamine intolerance. HIT patients often show dysbiosis and reduced alpha diversity. This includes decreased levels of beneficial bacteria associated with gut health—such as Bifidobacteriaceae, Butyricimonas, and Hespellia—and increased levels of potentially harmful bacteria, particularly Proteobacteria.

In addition, HIT patients have been found to harbor higher numbers of histamine-producing bacteria, including Escherichia coli, Lactobacillus vaginalis, and Morganella morganii. These microbes can contribute to higher histamine levels, increased inflammation, and are associated with inflammatory conditions such as asthma and IBD.

Key Takeaways

• Damage to the intestinal lining and leaky gut can increase histamine levels and worsen HIT symptoms.

• Dysbiosis and reduced alpha diversity are common in HIT patients, making restoration and maintenance of a healthy gut microbiome essential for symptom management.

• The relationship between histamine intolerance and gut health is a relatively new and complex research field, and further studies are needed to deepen our understanding.