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The link between the gut and the immune system in IBS


Mast cells are found in many parts of the body, but are concentrated in parts that are vulnerable to the outside world. The skin, the nasal passages, sinuses, the lungs and the gut. They are there to protect us but when levels rise above our tolerance, they can have a double edged sword & cause more issues than they should.

IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, ranging from constipation to diarrhea, and everything in between. Mast cells play a prominent role in the development of functional GI disorders, particularly IBS, reflux, & chronic or cyclical nausea. Mast cells are key components in inflammatory reactions. Upon activation, they release histamine, heparin, and nerve growth factor, among many other mediators that modulate immune response and nerve sensitization. This is important for pain perception/ hypersensitivity. Mast cell population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS).

As well as influencing gut nerve endings, proteases released by mast cells may also affect the integrity of the gut wall. The mucosal barrier acts as a semipermeable barrier allowing the absorption of nutrients but limiting the transport of potentially harmful antigens and microorganisms. Several studies have suggested that an increase in intestinal permeability could be a key factor of IBS progression. Overall, these studies clearly suggest that barrier function breakdown, with the possibility of bacterial invasion and low-grade immune system activation, plays an important role in the development of IBS symptoms, including pain hypersensitivity. This effect can be reinforced by the direct activation of mast cells in stressful situations. This highlights the consideration of IBS as a brain–gut axis disorder. Stress makes it worse.

Small intestinal bacterial overgrowth (SIBO) was shown to be common in those Mast Cell issues, as well as headaches, rashes, Postural Orthostatic Tachycardia Syndrome (POTS), period pain/ heavy periods. Diamine oxidase (DAO) is an enzyme that helps break down excess histamine in your body. We often are unable to make enough of this enzyme if we are low in zinc. Then what should be a normal level of histamine, begins to overflow and gut or allergy like symptoms can occur.

There is a histamine receptor on certain cells in the stomach that stimulates acid secretion. Many drugs used to reduce acid production are actually antihistamines. For example Zantac & Tagamet. These antihistamines are known as H2 blockers. Taking these longer term, has health implications, but the knowledge that they can be effective allows us to understand the mechanism of how histamine affects the digestive tract and then go on to use food / natural substances that can have a similar effect but without the risks.

Nutrients such as vitamin C, D & E, quercetin & antioxidants from fruits, berries, vegetables & green tea can help to stabilise mast cells and stop them releasing their contents. Hence the quality of the diet is important. Gluten and diets rich in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) have received significant attention. FODMAPs for some people are associated with the development of IBS /IBS-related symptoms. Changes in histamine levels, one of the key mediators released during mast cell activation, are reduced in IBS patients under a low FODMAPs diet, thus indicating why a low FODMAP diet can help. Please remember that a low FODMAP diet is designed to be a short term solution, to give relief from symptoms whilst you work on the underlying driver. Long term it will reduce bacterial diversity, and diversity is good for a healthy immune & digestive system.

Following a low histamine diet at least in the short term can be really life changing for some people. Histamine triggering foods include dairy, fermented drinks such as alcohol, vinegars, kombucha, kefir, as well as aged foods such as salami, deli meats, bacon, ham etc. Tinned foods such as tuna, or jarred/ preserved foods such as olives can also be an issue. Eating foods that have been in the fridge for several days will also cause increase in amine levels- this can trigger a histamine response. Fresh is best, especially for seafood.

So hopefully this article may give you an insight into the role histamine plays the development of IBS and other gut issues such as reflux and chronic nausea & ways that you can help to reduce the release of histamine by mast cells.

Lesley x

Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021 Apr 12;13(4):1262. doi: 10.3390/nu13041262. PMID: 33921522; PMCID: PMC8069563.

Uranga JA, Martínez V, Abalo R. Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use. Molecules. 2020 Sep 20;25(18):4314. doi: 10.3390/molecules25184314. PMID: 32962285; PMCID: PMC7570512.

Weinstock, L.B., Pace, L.A., Rezaie, A. et al. Mast Cell Activation Syndrome: A Primer for the Gastroenterologist. Dig Dis Sci 66, 965–982 (2021).

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