This blog, written by Tolerance, explores the link between small intestinal bacterial overgrowth (SIBO) and histamine intolerance, including how gut dysbiosis, histamine-producing bacteria and reduced diamine oxidase (DAO) activity may contribute to symptoms. Learn to recognise signs of histamine intolerance following SIBO treatment, understand the role of gut health and explore practical approaches to dietary management, client assessment and DAO supplementation.
You’ve been supporting a client with a course of antimicrobials for a case of SIBO. After their course, the bloating settles but the headaches and reactions to fermented and aged foods keep occurring. You don’t want to read this as the protocol having failed, but realise now that there must be something else occurring that was previously unidentified.
For many people, that additional factor is histamine. At Tolerance, histamine and food intolerance is our sole focus. Here we will set out the evidence that shows the link between histamine intolerance and SIBO and why clients can potentially develop histamine challenges during recovery from SIBO.
The histamine bucket
Histamine intolerance is often described as a bucket. Our internal histamine bucket fills from two sources: exogenous histamine that is eaten in food and drink, and endogenous histamine, which is released by the body's own mast cells. Diamine oxidase (DAO) is primarily produced in the small intestinal lining, and is the main enzyme responsible for degradation of histamine in the gut before it is absorbed. When the combined load outpaces clearance, the bucket overflows and symptoms follow.
That framing matters here because SIBO can act on both sides of the equation at once.
Histamine intolerance is heavily rooted in the gut
Schnedl and Enko conducted a review that argues that histamine intolerance is primarily a gastrointestinal disorder. They note that within the gut, DAO is the main enzyme degrading histamine from food and from the microbiota, and that DAO activity has been proposed as a marker of intestinal mucosal integrity. In inflammatory bowel disease, reduced DAO activity tracked the degree of mucosal damage.
The same study also places SIBO alongside IBS and functional dyspepsia as conditions whose symptom profiles overlap with histamine intolerance, and suggests measuring serum DAO in well-defined patients to help clarify this link.
Bacteria as a histamine source
Some gut bacteria produce histamine themselves. They carry an enzyme called histidine decarboxylase, which converts histidine from protein-rich foods into histamine. Where those bacteria are over-represented, they may contribute to the intestinal histamine pool, regardless of histamine obtained from food.
The clearest demonstration of this comes from animal work, although human evidence is growing. De Palma and colleagues colonised germ-free mice with faecal microbiota from patients with IBS, and identified Klebsiella aerogenes, carrying a variant of the histidine decarboxylase gene, as a major histamine producer. The histamine it generated drove visceral hypersensitivity through H4 receptor signalling.
In humans, the evidence sits at the level of microbial composition rather than cause and effect. Sánchez-Pérez and colleagues compared the gut microbiota of 12 patients with histamine intolerance against 14 healthy controls, and found significantly more histamine-secreting bacteria in the histamine intolerance group (including Staphylococcus, Proteus, Clostridium perfringens and Enterococcus faecalis), alongside significantly less of the bacteria generally associated with gut health. An earlier and smaller study by Schink and colleagues found elevated Proteobacteria and raised stool zonulin, which together point towards dysbiosis and an impaired intestinal barrier.
It’s worth noting that neither of these studies looked at SIBO specifically, and both were small in sample. Taken together, what they establish is the principle rather than demonstrating that the observed microbial differences cause symptoms.
The two-way pressure
This is where SIBO becomes relevant to the histamine bucket, because bacterial overgrowth in the small intestine could influence histamine exposure through the following two-way mechanism .
First, the translocation and overgrowth of histamine-producing bacteria in the small intestine, close to where absorption takes place.Second the inflammation that accompanies overgrowth affects the intestinal lining, which is where DAO is produced. This may result in more histamine being produced, and potentially reduced DAO enzyme available to clear it.
Sánchez-Pérez and colleagues make a similar point about dysbiosis more broadly. They suggest that an over-representation of histamine-forming bacteria could itself be one origin of histamine intolerance, and that the capacity to degrade that histamine would be easily overwhelmed in a client who already has a DAO deficiency.
It is worth clarifying that no study has yet tested this directly in SIBO patients, and the link between mucosal damage and reduced DAO production is evidenced in inflammatory bowel disease and coeliac disease rather than in SIBO. This mechanism should therefore be considered a hypothesis for further investigation, rather than an established explanation for persistent symptoms following a SIBO protocol.
What to look out for in clinic
The symptom overlap between SIBO and histamine intolerance is what makes this easy to miss. The pattern of symptoms, their relationship to food and their timing may help guide further assessment.
Things worth noting in a client who has received support for SIBO:
- Symptoms outside the gut that persist after treatment, particularly headache, flushing, urticaria, palpitations or rhinitis
- Reactions that cluster around aged, fermented, cured or leftover foods and alcohol, rather than around fermentable carbohydrates
- A partial response to a low FODMAP approach, which can be explained in part by the overlap between high-FODMAP and high-histamine foods
- Bloating that persists as the dominant complaint, which is as characteristic of histamine intolerance as it is of SIBO
- Other contributors to the bucket, including stress, alcohol, DAO-inhibiting medications (e.g. certain NSAIDs, antidepressants and diuretics) and conditions such as coeliac or inflammatory bowel disease
Serum DAO is worth interpreting with care. Schnedl and Enko note that serum values have not been established to correlate with DAO activity in the gut. Practitioners should also note that serum DAO levels fluctuate due to dietary, hormonal and external factors. Genetic testing can indicate a predisposition to reduced DAO production, but it cannot confirm a deficiency that has been acquired through gut damage or medication.
Sequencing the work
Where SIBO is confirmed within a client, addressing that remains the priority. The histamine question is usually best considered either alongside or after this initial work as the mucosa has the opportunity to recover.
A supervised, time-limited low-histamine elimination diet with structured reintroduction is the practical route to identifying personal thresholds and triggers. It should always remain an investigative tool rather than a long-term solution, as the restriction carries real nutritional risk, particularly vitamin C, omega 3 and magnesium deficiencies/insufficiencies. For this reason Tolerance always advises healthcare practitioner supervision of a low-histamine diet. It’s worth flagging to clients that a lot of foods pointed to in order to promote overall gut health (e.g. kefir, sauerkraut, kimchi, etc.) are fermented and naturally high in histamine, and may therefore not be suitable.
Where DAO supplementation fits
Aperitif, our DAO enzyme food supplement, is designed to be taken before histamine-rich food or drink to supplement the body's own DAO in the gut. It acts on dietary histamine, so in a SIBO context it sits alongside the work on bacterial load and mucosal recovery rather than in place of it. For some clients, DAO supplementation can form part of a broader plan while thresholds are being established, or it may be used to help reintroduce higher-histamine foods into the diet.
About Tolerance
Tolerance was founded by Andrew Sears and Sean Golding in 2024, and is the UK's only brand dedicated to histamine intolerance. Their first product, Aperitif, is a diamine oxidase enzyme supplement that contains 48,000 HDU per capsule, along with 15% of the RDI of vitamin C, an essential DAO cofactor. Tolerance partners with specialist nutritional practitioners and offers histamine genetic testing in partnership Lifecode Gx, all with one aim: helping people with histamine intolerance say yes to more of the food and drink they love. Tolerance has an extensive library of histamine related content on their website here.
References
- Schnedl WJ, Enko D. Histamine intolerance originates in the gut. Nutrients. 2021;13(4):1262.
- De Palma G et al. Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice. Sci Transl Med. 2022;14(655):eabj1895.
- Sánchez-Pérez S et al. Intestinal dysbiosis in patients with histamine intolerance. Nutrients. 2022;14(9):1774.
- Schink M et al. Microbial patterns in patients with histamine intolerance. J Physiol Pharmacol. 2018;69(4):579-593.