Histamine-producing gut bacteria is one of the leading causes of histamine intolerance I see in my client base.
It is well established that bacteria can produce histamine in fermented foods.
Still, an emerging body of research shows 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 sources of histamine in the human body.
Indeed, an imbalanced microbiome of the three root causes of histamine intolerance and mast cell activation.
Once the histamine-producing bacteria are addressed and the microbiome balanced, histamine tolerance is restored.
Here is a summary of some essential research on the role of our microbiome and histamine intolerance.
1. Histamine Producing Gut Bacteria Study 1
There has long been a hypothesis about a link between microbiota and asthma.
A recent study found the amount of histamine-producing bacteria in asthmatics was significantly higher than in non-asthmatics.
The histamine-secreting bacteria were escherichia coli, morganii morganii, and lactobacillus vaginalis, commonly associated with fish-related food poisoning. Furthermore, the higher the Morganii morganii, the more pronounced the symptoms.
As a result, increased levels of histamine-producing gut bacteria interact with histamine receptors to cause asthma symptoms.
2. Histamine Producing Gut Bacteria Study 2
It is well established that the immune system heavily depends on how the gastrointestinal tract handles histamine.
Depending on which histamine receptor is activated, histamine can have pro-inflammatory and anti-inflammatory effects on the immune system.
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.
In two other studies, it was demonstrated that higher histamine-producing bacteria blocked the anti-inflammatory H2 receptor.
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 had 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 the bacteria produces determines whether the immunoregulatory effects are pathological versus protective.
3. Histamine Producing Gut Bacteria Study 3
A 2017 study identified that the production or degradation of histamine and other biogenic amines was a key function of microbiota inhabitants.
A few strains could produce histamine at levels well above the maximum safety limits. However, the number increased dramatically when incubated with other biogenic amines (cavedeine and putrescine).
This led researchers to conclude that histamine appears to have a complex regulation system with other biogenic amines. For example, Escherichia coli, a histamine-producing bacteria well linked to histamine food poisoning, is only toxic because of other biogenic amines.
4. Histamine Producing Bacteria Study 4
In another 2017 study, 51 saliva samples collected from patients with respiratory problems were tested for 255 bacteria. Fifty strains of klebsiella pneumonia 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 can also be treated with herbs.
5. 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 64 participants, including 8 with diamine oxidase (DAO) deficiency and 25 with histamine intolerance (without DAO). DAO deficiency was not the sole driving factor.
The microbiome analysis showed that the histamine intolerant group had results suggestive of dysbiosis and intestinal barrier dysfunction.
6. Histamine Producing Bacteria Study 6
A 2022 study compared the microbiome composition of histamine intolerant and healthy individuals.
Dysbiosis of the gut microbiota was observed in the histamine intolerance group who, compared with the healthy individuals, had a significantly lower proportion of prevotellaceae, ruminococcus, faecalibacterium, and faecablibacterium prausnitzii, which are bacteria related to gut health.
They also had a significantly higher abundance of histamine-secreting bacteria, including the genera staphylococcus and proteus, several unidentified genera belonging to the family enterobacteriaceae and the species clostridium perfringens and enterococcus faecalis.
A greater abundance of histamine-producing bacteria would favor the accumulation of high levels of histamine in the gut, its subsequent absorption in plasma, and the appearance of adverse effects, even in individuals without DAO deficiency.
7. Histamine Producing Bacteria Study 7
A 2022 study also identified that klebsiella aerogenes was a hyper-producer of histamine.
The study also linked histamine-producing gut bacteria to irritable bowel syndrome.
In the study, histamine-producing bacteria activate histamine receptor 4 and attract mast cells to the colon leading to irritable bowel syndrome.
Beyond Individual Bacteria
The 2018 study raised the issue of whether the overall composition of the microbiota is more critical than the specific strains. Are we not seeing the forest for the trees?
The recent emergence of whole microbiota sequencing products has significantly increased our knowledge of the microbiome.
This has led researchers to conclude that the interaction between humans and the gut colonizing microbiota relies on mutualism.
Whereas we used to be focused on individual strains being good or bad, it is evident that a healthy microbiome can naturally balance itself.
Testing for Histamine-Producing Bacteria
Whereas we used to be focused on individual strains being all good or all bad for people with histamine intolerance, this is no longer our understanding.
Much can be achieved by giving the microbiome what it needs to balance itself. This includes the four Ps of good gut health, prebiotics, probiotics, polyphenols, and postbiotics, most of which can be obtained from our diet or supplements. A binder such as Toxaprevent or Zeobind can also be added in to bind histamine in the gut.
This is my preferred way of working initially.
However, when there are significant histamine imbalances, particularly to the hyper producers of histamine such as morganella species, klebsiella species, or klebsiella pneumoniae, then some anti-microbial treatment is typically needed.
My preferred test for assessing gut health remains The Gi-Map which tests for the following histamine-producing opportunistic bacteria:
Escherichia species, and
Research into the role of histamine-producing gut bacteria is still in its infancy.
Nevertheless, there is mounting evidence that one of the hidden sources of histamine intolerance is the gut microbiome.
Moreover, from a practical perspective, I am consistently reversing histamine intolerance by manipulating the microbiome alone.
I consider it one of the three root causes of histamine intolerance and mast cell activation.
Much progress can still be made without conclusive research, even among the most sensitive people.
To learn more about bacteria that activate mast cells, check out my blog post, Bacteria and Mast Cells: Rethinking Mast Cell Activation.
Almayah, A. A., and A. H. Issa. “Ibrahim Hk “Virulence factors and antibiotic susceptibility patterns of Klebsiella pneumonia strains Histamine producing bacteria isolated from sputum”.” Sci. J. Med. Res 1.4 (2017): 103-109.
Björnsdóttir-Butler, Kristin, et al. “Development of molecular-based methods for determination of high histamine producing bacteria in fish.” International journal of food microbiology139.3 (2010): 161-167.
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.
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.