In order to support the gut immune function nutrients and foods should address;
- Colonisation of the microbiota
- Production of SIgA
- Integrity of the mucosal epithelial layer
The colonisation of the microbiota and production of SIgA will indirectly also lead to the integrity of the mucosal epithelial layer as they are the first line of defence in addressing antigens that may cause damage to the epithelial layer. The microbiota also produce the SCFAs providing membrane integrity.
Probiotic & Prebiotic Foods
Probiotic and prebiotic foods are important to ensure a diverse gut microbiome. A diverse microbiome is supportive of gut wall integrity, Treg cell function, NK cell activity, production of cytokines, an appropriate immune response through interaction with GALT and the destruction of pathogenic bacteria.
Prebiotics are the food source for probiotics. Undigested fibre from prebiotic foods can be converted into the short-chain fatty acids (SCFAs) by bacteria in the colon. Butyrate in particular may improve intestinal function and integrity. Hence supporting the gut microflora through the consumption of pre and probiotic foods will not only allow the beneficial bacteria to colonise but also lead to the production of butyrate and the integrity of the intestinal wall. It has been shown that a low fibre diet increases the colonisation of mucus degrading bacteria resulting in a decrease of mucus.
Polyphenols are compounds within plants that are mainly indigestible by humans. They, therefore, are a food source for the gut microbiota and through the colonisation of the commensal bacteria result in the inhibition of pathogenic bacteria. They have in particular been shown to increase SCFA microbe producers Akkermansia and Bifidobacteria.
Compounds in garlic such as allicin that are non-nutritional but biologically active give garlic its age-old reputation as an antimicrobial. It has been shown to be effective against bacteria such as Salmonella, Escherichia, Klebsiella and Helicobacter. The mechanism of action explained is the inhibitory effect of allicin on sulfhydryl enzymes that can extend the life of microorganisms. Garlic has also been shown to have broad-spectrum antimicrobial activity against viruses, fungi and worms but there are few studies examining the mechanism of action.
The essential oils of oregano thyme and clove have all been studied for their antimicrobial activity. Essential oils are compounds in plants that give them their pungent taste and smell. Spices at culinary doses have also been associated with modifying the gut microbiota via prebiotic effects. Including culinary antimicrobials as part of everyday cooking will aid in maintaining the gut microbiota.
Curcumin has been shown to have a positive effect on the gut microbiome, intestinal permeability and have anti-pathogenic and antioxidant effects. Oral supplementation with curcumin has been shown to increase intestinal alkaline phosphatase (IAP) and consequently increase the deactivation of lipopolysaccharides (LPS). When LPS is deactivated a decrease in tight junction proteins is not expressed and the membrane integrity preserved. Curcumin also binds to the vitamin D receptor (VDR) on epithelial cells initiating cell signalling and an increase in tight junction proteins. Curcumin reduces the expression of cholesterol transporter and therefore there is a reduction in chylomicron secretion. LPS in the intestinal lumen is bound to chylomicrons and in this form translocated into the intestinal cells. With a reduction in chylomicrons, there is therefore a reduction in LPS translocation and damage to the intestinal layer.
Indigestible polysaccharides (large, complex sugar molecules) play a whole host of biological roles, from adding bulk to the stool, acting as prebiotic agents, through to delivering immunomodulatory activity. Beta-glucans, polysaccharides that are produced by bacteria, yeast, fungi and many plants, are very useful in supporting the immune system.
Beta-glucans have been studied for over 40 years. Much of this research has been carried out in Japan and the USA. These compounds have been shown to stimulate the production of NK cells, and also regulate T helper cells. For many years it was believed that beta-glucans delivered their activity on a lock and key basis. It was thought that there were receptor sites on the surface of specific leukocytes, that bound with beta-glucan in order to instigate an effect upon the cells impacting their behaviour.
However, this theory was reevaluated when beta-glucan was found intact in stool samples. It passed through the digestive tract intact yet still delivered its physiological effects of increasing NK cell numbers and interacting with the Th subgroup expression. Beta-glucan polysaccharides are similar in structure to polysaccharides displayed on the outer surface of some types of bacteria. It is now believed that when the beta-glucan polysaccharides pass over Peyer’s patches the immune cell detect this as being pathogen, and release cytokines, to recruit and stimulate the correct immunological responses. Beta-glucan has also been shown to increase the levels of SIgA.
Vitamin A is crucial to the health of mucous membranes of the gastrointestinal tract. Vitamin A improves cell migration and proliferation. IL-22 is a cytokine important in maintaining epithelial tight junctions and vitamin A is involved in the regulation of IL-22 responses. Retinoic acid (vitamin A) has also been shown to improve the intestinal barrier function by facilitating toll-like receptor 4 (TLR4) function. TLRs are membrane proteins that recognise microbes that have breached the physical barrier. They are found on the surface membranes of macrophages and dendritic cells and are part of the innate immune response. TLR4 recognises bacterial lipopolysaccharides (LPS) and other pathogen components produced during epithelial tissue damage.
Vitamin D upregulates key mucous membrane defence chemicals that defend the membranes against pathogen adhesion. Studies show that vitamin D supplementation aids in the epithelial membrane integrity hence reducing leaky gut. In one study patients suffering from Crohn’s disease and supplemented with 2000IU daily vitamin D for 3 months, had more intact intestinal linings than the control group. They also had lower levels of inflammation measured by C reactive protein levels. Investigations into the role of the vitamin D receptor (VDR) in maintaining intestinal barrier function have been performed and shown that VDR has a critical role in maintaining tight junctions by increasing the expression of Tight junction (TJ) proteins. Vitamin D deficiency increases the risk of leaky gut.
Glutamine provides gastrointestinal support, improving gut IgA levels and gut wall integrity. It increases the number of small intestine cells, the number and height of villi and regulates tight junctions. It is a fuel source for the proliferation and differentiation of the epithelial cells. Deficiency in glutamine has not only been shown to be associated with increased intestinal wall permeability but also supplementation can restore the integrity of the wall. L-Glutamine is described as a conditionally essential amino acid. This is because it can be produced from amino acids endogenously, however prolonged exercise and stress (including severe infections) result in L-glutamine depletion and exogenous glutamine is required under these conditions. Studies show that glutamine depletion results in mucosal ulceration and atrophy of the intestinal villi.
Zinc impacts a diverse number of mechanisms within the body including DNA replication, coenzymes including those involved in inflammation and anti-oxidation, immune cell function and regulation of apoptosis. Zinc deficiency has been shown to impact epithelial integrity due to changes in the TJs as well as inducing cell apoptosis.