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The Gut-Mast Cell Connection: SIBO, Digestion, and Supporting Gut Health
- Rachel Jessey
- Oct 15, 2023
- 12 min read
Updated: Apr 17
If you’re one of the many people with histamine intolerance or mast cell activation syndrome (MCAS), it is likely that you also struggle with gut issues - you are not alone, a large majority of people I work with who experience histamine or mast cell issues also present with some type of digestive problem.
The gut and mast cells have an intricate, two-way relationship. Inflammation in the digestive system can trigger mast cell degranulation and histamine release. At the same time, mast cell mediators circulating in the bloodstream can damage the intestinal lining, causing further gut issues. It’s a vicious cycle however, calming mast cells and histamine responses while supporting gut health helps to stabilise things.
In this post, we’ll cover the following topics:
The gut gases
Structural Causes of SIBO and Other Gut Problems
Poor Motility and Nerve Function
Other Causes of SIBO and Gut Problems
The Importance of Stomach Acid and Enzymes for Digestion
Butyrate and its nourishing effects on the gut lining.
How intestinal hyperpermeability can trigger mast cells.
My back-to-basics approach
Supporting the most sensitive of clients
Let’s get started with the gut gases
Deuterium vs. Hydrogen in the Gut
Hydrogen (¹H) is the most abundant element in the universe and a key byproduct of microbial fermentation in the gut. Deuterium (²H), sometimes called “heavy hydrogen,” contains one extra neutron and is naturally present at about 150 parts per million in water.
Certain gut microbes preferentially incorporate deuterium into metabolic intermediates, which can alter reaction rates or the stability of biomolecules.
Early research suggests that deuterium‑enriched molecules might influence cellular stress responses or redox balance. Though still hypothetical, shifts in local deuterium concentrations could subtly modulate gut epithelial health.
Hydrogen Gas: Friend and Foe
When carbohydrates reach the colon or small intestine, resident microbes ferment them, releasing hydrogen gas (H₂). While excess H₂ can lead to bloating, distension, and discomfort, it also carries potential benefits:
Antioxidant signaling: Low concentrations of H₂ can act as a selective antioxidant, neutralizing hydroxyl radicals without disrupting beneficial reactive oxygen species (ROS) involved in immune signalling.
Cellular protection: Animal studies have shown that inhaled or orally delivered hydrogen water can reduce intestinal inflammation and protect tight junction integrity.
However, symptomatically, H₂ accumulation often correlates with SIBO or carbohydrate malabsorption. The key is not to eliminate hydrogen producers entirely, but to balance gas production with efficient consumption pathways
.
Hydrogen Sulfide: The Antimicrobial Agent
Hydrogen sulfide (H₂S), notorious for its “rotten egg” odour, serves important functions in the gut:
Antimicrobial action: At micromolar concentrations, H₂S inhibits pathogenic bacteria by disrupting their respiratory enzymes and cell membranes. It also neutralises certain bacterial peptides that can trigger inflammation.
Mucosal signalling: Low levels of H₂S act as a gasotransmitter, promoting mucous secretion and enhancing epithelial repair. Crucially, too much H₂S can be toxic to host cells, so its production and consumption must be tightly regulated.
The Sulfur Pathway: From Sulfate to Sulfide
Sulfate uptake: Dietary sulfur (from cruciferous vegetables, proteins) enters the gut largely as sulfate (SO₄²⁻).
Activation: Sulfur‑reducing bacteria (e.g., Desulfovibrio spp.) convert sulfate to sulfite (SO₃²⁻) then to H₂S via the dissimilatory sulfate reduction pathway.
Detoxification: Other microbes (e.g., Bilophila wadsworthia) and host enzymes oxidise excess H₂S back to thiosulfate or sulfate, preventing accumulation.
Maintaining a balanced community of producers and consumers is critical. Disruption from antimicrobial interventions such as by antibiotics and herbs that wipe out H₂S‑oxidisers, can lead to H₂S buildup and mucosal damage.
Methane’s Role: Capturing Hydrogen and Carbon
Methanogenic archaea consume H₂ and carbon dioxide to produce methane (CH₄). This process:
Reduces hydrogen pressure, preventing excessive H₂ accumulation and related symptoms.
Channels carbon into CH₄, which is excreted, thus removing excess fermentative carbon from the system.
But methane is not inert in the host:
Histamine modulation: Methanogens can influence the levels of histamine‑producing bacteria, potentially by competing for H₂ or altering local pH. Since histamine affects gut motility and inflammation, this has clinical relevance for histamine intolerance.
Methylation cycles: Some pathways intersect with methyl groups: for example, methylotrophic archaea use methane to generate methyl donors that can feed into folate‑mediated one‑carbon metabolism, influencing DNA methylation and epigenetic regulatio
Structural Causes of SIBO and Other Gut Problems
When dealing with chronic gut issues, it’s important to first rule out any anatomical or structural factors that could be contributing. For example, a hiatus hernia, prolapse, adhesions, a tilted pelvis or even surgical procedures such as a hysterectomy can all mechanically alter the shape and function of the digestive tract. Nerve damage, dysautonomia or irritation in the abdominal region can also impair proper motility and flow.
First and foremost it is important to consult with a medical professional prior to seeking holistic support because if there is something structurally out of balance or something needs medical intervention then this needs to be addressed as a priority.
Poor Motility and Nerve Function
Assuming no major anatomical abnormalities are found, the next thing to explore is gut motility, which is simply defined as the movement and flow of food through the digestive tract. Mast cells release histamine that alters gut contractions, so calming mast cells may restore motility and gastrointestinal function.
There are also a few interrelated factors that impact motility:
Stomach acid production
Digestive enzyme levels and bile flow
Vagal tone
Migrating motor complex (MMC) function
Inefficient stomach acid production is incredibly common in my clinical practice. This condition is otherwise known as hypochloridria, it hampers digestion and contributes to changes in the gut microbiome. Stomach acid production naturally declines with age, which is one reason why many people find meat hard to digest as they get older because stomach acid helps with the breakdown of protein. Inefficient stomach acid also occurs when you lack vital nutrients such as chloride, zinc and vitamin B1, however infections, food poisoning, or medication use can also contribute to this. One of the most inappropriately used medications in the world are called proton pump inhibitors (PPI’s), such as omeprazole or lansoprazole. Very often people are left on these medications for far too long. Continuous suppression of stomach acid contributes to nutritional deficiencies and negatively affects the health of the gut microbiome and increases the risk of colonisation of pathogenic microbes, including Clostridium difficile and salmonella. Research has found that people on long term PPI have a higher prevalence of oral cavity bacteria translocating to the gastrointestinal microbiome. If you have been on long term PPI medication, please discuss these risks with your GP.
Low digestive enzyme levels and poor bile flow can also impair the break down of foods, undigested food can feed opportunistic bacteria and yeasts that contribute to SIBO type symptoms, which includes excessive burping, gas, indigestions and painful bloating.. Bile is equally important, not only with helping to digest and absorb fats and vitamins A, D, E and K, but bile helps to produce and environment where pathogenic microbes do not have the opportunity to overgrow and proliferate.
The vagus nerve serves as a highway that sends signals promoting motility. Vagus nerve damage or imbalance has a profound effect on digestion. This manifests as either constipation or chronic diarrhoea, but the vagus nerve also regulates the opening and closing of the sphincters of the stomach, the contraction of the gallbladder and the release of pancreatic juices. In my most sensitive of cases, dietary and supplementation interventions do not work until nervous system imbalances have been addressed and I refer these people on the DNRS programme or to a polyvagal expert.
The migrating motor complex (MMC) are responsible for sweeping debris out of the small intestine between meals. To work properly, it requires a period of “down time” of around 3-4 hours after eating. Frequent snacking inhibits the action of MMC. Bacterial-produced metabolites can directly influence gut motility, leading to a cascade of effects and feedback mechanisms impacting the production of the metabolite itself. Gut bacteria replicate and produce their metabolites based on the availability of nutrients. Metabolites impact gut motility, which, in turn, modifies the fluid flow.
The takeaway from all of this is that supporting motility requires a multi-pronged approach some of those approaches may include:
Supplement to support stomach acid and digestive enzyme production
Support for healthy bile flow
Vagus nerve exercises
Allowing 3-4 hours between meals for MMC activation
Identify any food intolerances of other causes listed below
Other Causes of SIBO and Gut Problems:
Aside from anatomical and motility factors, there are a few other potential causes of SIBO and gut issues to rule out:
Previous history of food poisoning
Medications like PPIs or antibiotics
High stress levels
Nutrient deficiencies
Underlying infections and pathogens
Spike protein persistence
Mould toxicity
Blood sugar imbalances
Thyroid dysfunction
Of relevance for those with mast cell activation is mould toxicity which is almost certainly a common trigger for both digestive symptoms and histamine intolerance and this is something that I see time and time again in my practice.
High cortisol from chronic stress also negatively impacts digestion, immunity, and the microbiomes, so stress management becomes an important factor in supporting gastrointestinal health.
The Importance of Stomach Acid and Enzymes for Digestion
I've hinted a few times to the importance of stomach acid (HCl), digestive enzymes, and optimal bile flow for effective digestion on several occasions. Let's delve deeper into these crucial aspects.
Insufficient HCl can hinder the efficient breakdown of food particles. This not only places extra demands on digestive enzymes and bile but also leads to bacterial fermentation further up in the small intestine. This is a contributing factor to the development of SIBO, as low stomach acid allows for its progression. HCl also plays a pivotal role in activating the enzyme pepsin, necessary for protein digestion, and intrinsic factor, which aids in B12 metabolism. Moreover, ferric iron, the primary form of iron in plant foods, requires an acidic environment with a pH of 3 or lower to maintain stability for optimal absorption. This explains why individuals with SIBO may encounter nutritional deficiencies.
Pancreatic enzymes, released from the pancreas into the small intestine, rely on the presence of an acidic chyme from the stomach to function effectively. In the absence of this acidity, their impact is compromised. Furthermore, low stomach acid interferes with the initiation of the migrating motor complex, as previously discussed. In summary, low stomach acid sets the stage for incomplete digestion, bacterial overgrowth, and impaired motility—a perfect combination contributing to SIBO.
While Betaine HCL, digestive enzymes, and bile acids are frequently used interventions, I prefer to explore more natural approaches. These include incorporating bitter foods, supporting the nervous system, and naturally elevating stomach acid levels through optimising saliva production and thorough chewing.
Butyrates role in the digestive tract
Butyrate and other short chain fatty acids (SCFAs) play several important roles in gut health:
Serve as fuel for enterocytes (intestinal cells).
Modulate gene expression and inflammation.
Improve gut barrier integrity.
Increase absorption of vitamins and minerals.
Butyrate is also an HDAC inhibitor and anti-inflammatory that helps calm mast cells. It’s been shown in studies to reduce allergic reactions.
The primary issue I often observe in most SIBO intervention protocols is the exclusion of foods that promote a healthy microbiome, along with the use of potent anti-fungals followed by the introduction of probiotics. and excessive amounts of butyrate supplementation. I believe this approach may further exacerbate the dysregulation of the gut microbiome. I'll delve deeper into the shortcomings of current SIBO protocols and the issue of probiotic and butyrate contamination in a separate post.
Returning to the topic of butyrate, this short-chain fatty acid is produced through the fermentation of resistant starches. Research consistently demonstrates that resistant starches play a pivotal role in shaping the gut microbiome and producing not only butyrate but also other essential short-chain fatty acids. While butyrate is available in supplement form, it's essential to recognise that butyrate production involves a complex interplay between dietary components and gut microbes. Flooding the gut with an end-stage metabolite like butyrate may potentially exacerbate existing imbalances. Incorporating resistant starches into your diet can be easily achieved by consuming overnight oats, cooked and cooled potatoes, and rice.
Intestinal permeability or leaky gut:
Another crucial aspect to consider is intestinal hyper-permeability, commonly referred to as "Leaky Gut." Mast cell activation syndrome is known to increase intestinal paracellular permeability, in simple terms, widening the gaps between the cells lining the gut. This permits the passage of intestinal metabolites into the systemic circulation, triggering an immune response. This sets in motion a vicious cycle of mast cell activation, originating from the initial source and now compounded by the leaky gut mechanism.
Limitations of the Functional Medicine SIBO Model and the Pitfalls of “Killing Off”
Most functional medicine protocols for SIBO emphasise two core steps: (1) starving or eradicating excess bacteria with strict diets or antimicrobials, and (2) repopulating with “beneficial” microbes via probiotics. While this approach often yields short‑term symptom relief, it overlooks several key aspects of gut ecology and gas dynamics:
Collateral Damage to Gas‐ConsumersBroad‑spectrum antibiotics, herbal antimicrobials, and elemental diets don’t distinguish between “bad” fermenters and essential hydrogenotrophs (methanogens, sulfate‑oxidizers). Eliminating these gas‑consumers removes critical sinks for hydrogen and sulfide, leaving behind a system still prone to gas buildup, dysbiosis, and symptom recurrence.
Neglect of Sulfur and Isotope Pathways
By focusing solely on bacterial counts, traditional protocols ignore how sulfur‑reducing and -oxidizing microbes maintain mucosal health through controlled H₂S signaling, or how deuterium content might modulate microbial enzyme activity. Without supporting these pathways, you can’t restore the gut’s full metabolic network.
Rebound Overgrowth and Opportunism
“Sterilising” the small intestine creates ecological voids. Pathogens or fungi can rapidly colonise these niches, often leading to more severe dysbiosis than before. In effect, you trade one overgrowth for another.
Short‑Sighted Biomarker Focus
Breath tests measure H₂ and CH₄ but say nothing about isotopic ratios, sulfide flux, or downstream effects on histamine and methylation cycles. Eradication protocols that reduce breath hydrogen may look successful on paper, yet leave deeper imbalances unaddressed.
Missed Therapeutic Opportunities
Rather than indiscriminate killing, a more nuanced strategy would dampen pathogenic fermenters while nurturing hydrogenotrophs, sulfide‑oxidizers, and pathways that channel gases into beneficial signalling or safe excretion.
In summary, the conventional functional medicine SIBO model treats symptoms by “clear‑cutting” the microbiome, but this blunt approach can disrupt the very gas‑cycling and isotope‑mediated systems vital for long‑term gut resilience. A precision strategy—one that balances eradication with ecosystem support—is essential for durable recovery.
Things that you can do
Step 1: Start with a low deuterium food plan, natural spring water or sparkling water if tolerated.
Step 2: Next, focus on optimising digestive function by targeting the gut-brain axis. The approach will vary depending on the severity of symptoms.
Step 3: Balance redox reactions, by aligning circadian biology, getting in nature and supporting vagal tone
Step 4: Improvement in the microbiome often becomes apparent after implementing the initial three steps. However, specific support may be required for the oral, nasal, and gut microbiomes.
In conclusion, while I've suggested various interventions within this discussion, it is crucial that individuals collaborate with a knowledgeable practitioner well-versed in histamine-related issues to uncover any underlying factors contributing to leaky gut and SIBO, such as infections or digestive dysfunction. Keep in mind that supplements can interact with medications, so it's imperative to conduct a comprehensive assessment of drug-nutrient interactions before incorporating supplements. Additionally, if you have structural issues within your digestive tract, hernias, gallstones, cysts, adhesions, a predisposition to bowel blockages, kidney disease, or cancer, DO NOT self-prescribe supplements. Always seek the guidance of a qualified professional.
With patience and an integrated approach, you can break the cycle of gut issues provoking mast cell activation and vice versa.
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