Mast Cells and IBS- What is the Connection?

Mast cells are a type of immune cell and are of importance when it comes to the initiation of inflammation within the body. 

When activated they release many different compounds or mediators (see list below) that influence the body’s immune system response. Mast cells are typically found around blood vessels, neurons, muscle cells, glands, and hair follicles.

They are the highest concentrations inside the body, such as in the intestinal mucosa, where pathogens, allergens, and other environmental agents are met.

Examples of several mast cell mediators:

• Amines (histamine, dopamine, polyamines)
• Proteases (tryptase, chymase, carboxypeptidase A)
• Cytokines (tumor necrosis factor, interleukins)
• Chemokines
• Growth factors
• Peptides
• Reactive oxygen species
• Phospholipid metabolites (prostaglandin E2)

With IBS-D (diarrhea), research has shown that there is an increase in mast cells in the colon mucosal lining leading to an increase in mast cell mediators. An increase in mediators like prostaglandin E2, tryptase, histamine, and cytokines has been shown to cause gut epithelial barrier loss in animal models- suggesting this could lead to leaky gut or gut permeability.

Additionally, animal studies identified that rodents fed diets high in fructose-oligosaccharides and fructose had an increase in gram-negative bacteria resulting in increased lipopolysaccharide (LPS). LPS can also lead to increased gut permeability which triggers inflammation both locally (in the gut) and systemically (throughout the body). This increased inflammation from LPS can possibly trigger mast cell activation. This suggests that FODMAP-induced IBS symptoms might involve mast cell activation.

A 2021 study conducted by Singh et al. found that a diet high in FODMAPs (this induces gastrointestinal symptoms in patients with IBS) led to greater concentrations of mast cell activation within the colon and led to colonic barrier loss due to increased LPS (lipopolysaccharide) levels. They demonstrated that a Low FODMAP diet improved colonic barrier function and overall reduced mast cell activation and decreased fecal LPS levels. This is important to note, as following a Low FODMAP diet has been shown to reduce the severity of IBS in symptomatic individuals.

In addition to a LOW FODMAP diet, there is more ongoing research to identify if other nutrient-derived bioactive compounds (aka nutraceuticals) can influence mast cell activation by reducing the compounds released during mast cell activation which may result in reducing gut permeability and inflammation.

The components that are actively being investigated include:

• Lipids

• Fatty acids (alpha lipoic acid, EPA, DHA, acetate, propionate, and butyrate)

• Cannabinoids (cannabidiol, palmitoylethanolamide)

• Fat-soluble vitamins (vitamin D and vitamin E)

• Amino acids (glutamine and arginine)

• Carotenoids (antioxidant activity)

• Polyphenolic compounds (flavonoids, curcumin, cinnamon extract, or cinnamaldehyde)

If you have IBS, talk with a registered dietitian to learn more about the Low FODMAP diet and to discuss other nutrition interventions that may be appropriate for you. Hopefully, soon, there will be more research outlining further recommendations for the management of IBS symptoms and ways to target gut-induced inflammation. Stay tuned!

1. _{Grabauskas, G., Wu, X., Gao, J., Li, J.-Y., Turgeon, D. K., & Owyang, C. (2020). Prostaglandin E2, produced by mast cells in colon tissues from patients with irritable bowel syndrome, contributes to visceral hypersensitivity in mice. Gastroenterology, 158(8).}
2. _{Singh, P., Grabauskas, G., Zhou, S.-Y., Gao, J., Zhang, Y., & Owyang, C. (2021). High fodmap diet causes barrier loss via lipopolysaccharide-mediated mast cell activation. JCI Insight, 6(22).}
3. _{Uranga, J. A., Martínez, V., & Abalo, R. (2020). Mast cell regulation and irritable bowel syndrome: Effects of food components with potential nutraceutical use. Molecules, 25(18), 4314.}
4. _{Zhou, S.-Y., Gillilland, M., Wu, X., Leelasinjaroen, P., Zhang, G., Zhou, H., Ye, B., Lu, Y., & Owyang, C. (2017). FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction. Journal of Clinical Investigation, 128(1), 267–280.}