HISTAMINE PRODUCING GUT BACTERIA

Histamine producing gut bacteria is one of the leading causes of histamine intolerance in my clients.

It is well established that histamine can be produced by bacteria and yeasts in fermented foods, but there is an emerging body of research, showing that the microbes within the human gut can also produce, regulate, or degrade histamine.

We can therefore no longer assume that mast cells and basophils are the sole source of histamine in the human body.

Indeed, one of the key sources within my client base is dysbiosis or an imbalanced microbiome.  

Once the histamine producing bacteria and yeast are addressed the histamine intolerance reverses.

Despite this clinical experience, the research is still emerging. Here is what we know so far.

Histamine Producing Gut Bacteria Study 1

There has long been a hypothesis that there is a link between the microbiota and asthma.

A recent study found the amount of histamine producing bacteria in asthmatics was significantly higher than non-asthmatics.

Interestingly, the type of histamine secreting bacteria was Escherichia coli, Morganii morganii, and Lactobacillus vaginalis commonly associated with fish-related food poisoning. Furthermore, the higher the levels of Morganii morganii the more pronounced the symptoms. 

As a result is hypothesized that increased levels of histamine producing gut bacteria, interact with histamine receptors, to cause the asthma symptoms.

Histamine Producing Gut Bacteria Study 2

It is well established that the immune system is heavily dependent on how the gastrointestinal tract handles histamine.

Histamine can have both pro-inflammatory or anti-inflammatory effects on the immune system depending on which histamine receptor is activated.

There are currently four known histamine receptors. 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.

However, in one study, it was demonstrated that moderate histamine producing bacteria, stimulated the inflammatory H1 receptor. Whilst in two other studies, it was demonstrated that higher histamine producing bacteria blocked the anti-inflammatory H2R.

Interestingly, histamine levels are increased in patients with irritable bowel syndrome and inflammatory bowel disease, and it was recently shown that inflammatory bowel disease patients have decreased H2 receptor function. Could this be due to very high levels of histamine producing gut bacteria?

It is hypothesized that the amount of histamine produced by the bacteria determines whether the immunoregulatory effects is pathological versus protective. This hypothesis is consistent with research into the progression of mast cell activation.

Histamine Producing Gut Bacteria Study 3

A recent 2017 study, identified that the production or degradation of histamine and other biogenic amines was a common function of microbiota inhabitants. That is it was a key not an incidental function.

A small number of strains could produce histamine at levels well above the maximum safety limits, however, the number increased dramatically when incubated with other biogenic amines (particularly cavedeine and putrescine).

This led researchers to conclude that histamine appears to have a complex system of regulation with other biogenic amines. For example, Escherichia coli, a histamine producing bacteria well linked to histamine food poisoning, is only toxic because of the presence of other biogenic amines.

Histamine Producing Bacteria Study 4

Another 2017 study, of 51 saliva samples, collected from patients with respiratory problems, was tested for 255 bacteria. 50 strains of Klebsiella pneumoniae were identified, and 11 of the 50 strains, were histamine producing. Histamine concentrations were at levels sufficient to cause histamine poisoning.

Klebsiella pneumoniae was found to be able to be treated with the antibiotic Trimethoprim. In my experience, Klebsiella pneumoniae is also able to be treated with herbs.

Histamine Producing Bacteria Study 5

A 2018 study looked at the intestinal bacterial composition in patients with proven histamine intolerance compared to healthy persons.

The study had a total of 64 participants, including 8 with diamine oxidase (DAO) deficiency and 25 with histamine intolerance (without DAO deficiency). Clearly, DAO deficiency is not the sole driving factor.

The microbiome analysis showed that the histamine intolerant group had results suggestive of dysbiosis and intestinal barrier dysfunction. 

List of Histamine Producing Gut Bacteria

There needs to be a fair degree of caution in relying upon the lists that follow. This list will emerge and be refined with further research.

Firstly, these lists are of species, not strains, and it is the strains that determine the histamine reaction. I have not listed the strains as the gastrointestinal tests do not currently report them.

Secondly, there are no large-scale studies, of the 10,000s of microbial species. Most major studies look at no more than 125 strains.  Given what seems to be a complex interplay between the microbiome these types of studies are needed.

Thirdly,  many of the earlier studies are not of the human gut biome. I have included high histamine strains where there is a high degree of consensus.  This is imperfect. A more conclusive list will emerge in time.

With those caveats here is a list of what we know to date.

Bacteria that produce histamine

 

The 2017 study highlighted for the first time that many microbial strains can become histamine producing in the presence of other biogenic amines.

The above table lists the bacteria which produce other biogenic amines. Those with extensive biogenic amines are known to be exceptionally high histamine producers and mast-cell degranulation. 

Beyond Individual Bacteria

The 2018 study raised the issue of whether the overall composition of the microbiota is more important than the specific strains. 

Are we not seeing the forest for the trees? 

The recent emergence of whole microbiota sequencing products such as Thyrve and BiomeFX has generated a significant increase in our knowledge of the microbiome. 

This has lead researchers to conclude that the interaction between humans and the gut colonizing microbiota relies on mutualism. 

The key interrelationships I have found that point to histamine intolerance is: 

  • Low diversity of microbiomes.
  • The association between phyla (classes) of bacteria is more important than individual bacteria. Phyllums are divided into gram-negative and gram-positive bacteria. Gram-negative bacteria (especially Proteobacteria - as above, and Bacteroides - which include many pathogens) are highly indicative of histamine intolerance.
  • Bifido and lactobacilli are the central link in the colon microbiota. High levels of these bacteria are highly indicative of histamine intolerance.
  • Butyrate producers are crucial to controlling gut inflammation and mast cells. The use of butyrate supplements can have a dramatic impact on inflammation and mast cells.
  • Helicobacter Pylori because it contributes to leaky gut.

What I have found is that a significant amount of dysbiosis can be addressed by manipulating the gut biome itself, however, some infections create such a disruption in the microbiome environment that it is expeditious to treat them in their own right. 

Conclusion

Research into the role of histamine producing gut bacteria is still in its infancy. 

Never the less there is mounting evidence that one of the hidden sources of histamine intolerance is the gut microbiome.

Whats more from a practical perspective I am consistently reversing histamine intolerance through manipulation of the microbiome alone.  

In the absence of conclusive research, much progress can still be made even in the most sensitive people. 

References

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Ferstl, Ruth, et al. "Histamine receptor 2 is a key influence in immune responses to intestinal histamine-secreting microbes." Journal of Allergy and Clinical Immunology 134.3 (2014): 744-746.

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Huang, Yvonne J., et al. "The microbiome in allergic disease: Current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology." Journal of Allergy and Clinical Immunology 139.4 (2017): 1099-1110.

Özogul, Fatih, and Yesim Özogul. "The ability of biogenic amines and ammonia production by single bacterial cultures." European Food Research and Technology 225.3-4 (2007): 385-394.

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Kim, Shin-Hee, et al. "Identification of bacteria crucial to histamine accumulation in Pacific mackerel during storage." Journal of food protection 64.10 (2001): 1556-1564.

Björnsdóttir-Butler, Kristin, et al. "Development of molecular-based methods for determination of high histamine producing bacteria in fish." International journal of food microbiology 139.3 (2010): 161-167.

Kim, Shin-Hee, et al. "Identification of the main bacteria contributing to histamine formation in seafood to ensure product safety." Food Science and Biotechnology 12.4 (2003): 451-460.

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Smolinska, S., et al. "Histamine and gut mucosal immune regulation." Allergy 69.3 (2014): 273-281.

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