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Histamine & Gut Health

Histamine & Gut Health
Histamine & Gut Health
Scientific studies show that histamine intolerance and the gut microbiome are connected. Here, we outline histamine's effect on the gut mucosa, how a leaky gut can worsen your histamine intolerance, and which specific microbes play vital roles.


This is part 2 of the Histamin series. Read part 1: Histamine Intolerance and part 3: Histamine and Irritable Bowl Syndrome(IBS) to get a bigger understanding about histamine and histamine intolerance. 


The current state of the art

Histamine is a signal molecule with broad effects throughout the body, as described in (Histamin part A). White blood cells, such as mast cells and basophils, produce histamine, as do certain microbes. Histamine is present in relatively high levels in the gastrointestinal tract, especially during inflammatory responses. Low levels of DAO, one of the enzymes which break down histamine, is typically the cause of a histamine overload which leads to the symptoms of histamine intolerance (HIT).


Histamine's effect on the gut mucosa 

The mucous membranes in the body are in constant contact with microorganisms, food, and inhaled antigens and works as a first line of defense. Mucosal surfaces are also the home of the microbiome, with an essential role for the host's health, such as to support the immune system. 

 In the gut, the mucous lining (filled with histamine-producing mast cells) protects the intestinal wall from irritants. If this mucous lining is disturbed (e.g., as a result of dysbiosis) and particles from food touch the wall directly, it will irritate and cause an immune response and trigger the mast cells to release histamine (and other compounds) as a safety mechanism. Over time, this will result in excess levels of histamine in the body.  

Additionally, the mucus lining constantly produces and releases DAO, which ensures the breakdown of histamine, both from foods and produced by microbes in the gut. Gut dysbiosis promotes mucosal inflammation and damage of the DAO-producing cells, which results in reduced levels and function of DAO and therefore inefficient breakdown of histamine. Increased histamine levels in the body will then occur, followed by HIT symptoms.  


A leaky gut can affect the histamine release

The intestinal wall is responsible for selective permeability: letting the good stuff (vitamins, minerals, etc.) enter the body, and keeping the bad stuff (toxins, pathogens, whole food particles) out of the body. This is ensured by barriers, including a layer of epithelium cells tightly packed and held together. However, if this layer is disturbed, unwanted particles can leak out to the bloodstream, resulting in the condition known as “leaky gut”.

 Abnormal compounds in the bloodstream are a threat to the immune system and result in inflammation, which trigger the release of histamine. With a leaky gut, this inflammation becomes constant, which may result in excess histamine and HIT symptoms. 


 The relation between the gut and HIT  

A disturbed microbiome is suggested to be a main driver behind histamine intolerance. Gut dysbiosis and reduced alpha-diversity are frequently observed in HIT patients. This is shown by reduced abundances of bacteria related to gut health: Bifidobacteriaceae, Butyricimonas and Hespellia, as well as increased levels of the more harmful bacteria Proteobacteria. 

 Furthermore, HIT patients have shown to  have more histamine-producing bacteria in the gut,  such as Escherichia coli, Lactobacillus vaginalis, and Morganella morganii. This may contribute to higher levels of histamine in the body, more inflammation, and is linked to inflammatory diseases, such as asthma and IBD. 


Take away messages

  • Both mucosal inflammation and leaky gut may contribute to higher levels of histamine and therefore symptoms of HIT.
  • Gut dysbiosis and reduced alpha-diversity is observed in HIT patients, so restoring and maintaining a healthy gut microbiome is important to improve the symptoms of HIT.
  • Histamine intolerance and gut health is a relatively new field of research, and further studies are required to. 

Author:  Ingeborg Amble Holtmann