Microbiome and the Influence on the Immune System
Microbiome and the Influence on the Immune System:
The composition of the microbiome can be a factor of susceptibility of the basic function of the immune system. The gut microbiota also regulates many aspects of innate and acquired immunity, protecting the host from pathogen invasion and chronic inflammation (Mallappa et al., 2012). Recently, investigators related the imbalances in gut microbiota with susceptibility to infections, immune-based disorders. In addition, the gut microbiota is also demonstrating associations with obesity and insulin resistance. For example, numerous studies indicate that the host microbiome can influence susceptibility to certain microbes such as Campylobacter, which is often seen in anxiety disorders. In fact, a book by Martin Blaser called “Missing Microbes” discusses that the alteration of the human microbiome could be one of the factors attributed to the rise of conditions such as food allergies, asthma, celiac disease and intestinal disorders such as IBD. His theory is that the modern medical practices, that includes overuse of antibiotics, may have negatively shifted the microbiome in a way that is affecting human health detrimentally. “The use of antimicrobial drugs is known to be associated with the development of certain infectious diseases, such as colitis and candidiasis, through disruption of the host-associated microbiome” (Casadevall and Pirofski, 2018). It is hypothesized that the establishment of this microbiome occurs during the first 3 years of life, and disruptions in this establishment during this time can have long term implications (Blaser, 2016). For example, 50% of babies in the US are born by C-section, and this can be the beginning of some of the various disruptions in the delicate microbiome balance. This is not limited to bacteria, but also fungal and viral elements of the microbiome, that are also demonstrating a role in human health as well.
Nutritional intervention: Probiotics
A nutritional intervention to address the microbiome is the use of probiotics. Probiotics are defined by the World Health Organization as “live microorganisms that can provide benefits to human health when administered in adequate amounts, which confer a beneficial health effect on the host” (WHO/2001). Probiotics are live organisms that, when ingested in adequate quantities, exert a health benefit on the host. Probiotics can directly stimulate the growth of beneficial bacteria and competitively exclude the number of more harmful, toxin producing microbiota (Zhou & Foster, 2015). Lactobacillus, Bifidobacterium, and Saccharomyces are three extensively studied and commonly used probiotics in humans and animals. S. boulardii, for example, can induce higher levels of IL-10 and SIgA, which gives it characteristics of immunomodulation in the intestine (Vieira, Teixeira, & Martins, 2013). Some studies indicate that Saccharomyces cerevisiae strain 905 can significantly reduce the translocation and dissemination of some pathogenic bacteria such as Salmonella typhimuirium after oral infectious challenges in lab mice.
Four main beneficial effects of probiotics on the intestinal mucosal defense system include the following:
- Probiotics can block pathogenic bacteria by producing substances that directly compete with pathogens for adherence to the intestinal epithelium.
- Probiotics can enhance intestinal barrier function and stimulate protective responses from epithelial cells. This can lower the chance of bacteria translocating into the blood stream and entering systemically. This function may decrease infections and immune related reactions, thus supporting the health of the immune system (Enviormedica, n.d).
- Probiotics are able to modulate the immune system and pathogen induced inflammation through TLR regulated signaling pathways.
- Probiotic treatment can elevate SIgA in the intestine, as well as IgA and IgM in the serum and also increase the production of the anti-inflammatory cytokine: IL-10 (Vieira et al., 2013).
Nutritional intervention: Prebiotics
Prebiotics are defined as food ingredients composed of oligosaccharides that are not digestible by the host. They have a beneficial effect on host health through selective stimulation of the growth of specific members of the gut microbiota (Vieira et al., 2013). Currently, inulin and galactooligosaccharides that are present in certain plants as storage carbohydrates fulfill the criteria as a prebiotic. Any type of dietary food that can promote the growth of beneficial bacteria and promote gut health can be considered a prebiotic. These include fiber carbohydrates (cellulose, pectin, gums, beta-glucan, lignin) that are not digested in the upper GI tract. It is thought that these substances can be selectively fermented in the colon by residential bacteria into short-chain fatty acids (SCFA’s) such as acetate, propionate, butyrate, and lactate (Vieira et al., 2013). A decrease in healthy microbiota and SCFA’s is characteristic of patients with IBD. One of the most studied SCFA’s is butyrate, as it is a major energy source of colonic epithelial cells that can affect the barrier function and reduce oxidative DNA damage. “Butyrate, which is more highly produced on a resistant starch, soluble fiber and inulin diet, was also associated with increased percentages
Diet has the strongest and most direct effects on gut microbial colonization due to the bacteria’s preference for different energy sources. Over the past decades, our diet has changed dramatically. The consumption of fiber has decreased and there is an increase in high fat, high calorie, processed foods. This happens to correlate with the number of people affected by inflammatory diseases that is on the rise. It seems likely that the change to the Western diet is accompanied by altering our microbiota and increasing the susceptibility to inflammatory disease.
“Thus, diet is closely related to the species present in the gut microbiota” (Vieira et al., 2013). The two most abundant phyla are Bacteroidetes and Firmicutes. The fiber in food can significantly shift the gut microbiota composition and directly affect the mucosal immune system, which can possibly result in improvement in inflammatory disorders and enhance the immune response. The molecular mechanisms that might explain how a diet enriched in fiber affects the immune system is starting to surface. Other protective mechanisms are involved besides production of SCFA’s:
- Prebiotics can provide resistance to colonization by pathogenic bacteria by inhibiting the adherence of pathogens on the gut epithelium (Vieira et al., 2013).
- Prebiotics can prevent diarrhea and constipation
- Prebiotics can exert positive effects on lipid metabolism
- Prebiotics can stimulate mineral adsorption
All of the above are indirectly mediated by regulation of the intestinal microbiota. “Given the strong immuno-modulatory function of SCFAs, the production of microbe-derived metabolites using prebiotics is being explored as a promising avenue for prophylactic and therapeutic intervention in gut inflammation” (Vieira et al., 2013). As a result, studies on prebiotics are exploding in search of promising new therapies to treat disease and adjuvant therapy along with probiotics, forming symbiotics.
Probiotics can regulate host innate and adaptive immune responses by modulating the functions of dendritic cells, macrophages, and T and B lymphocytes. One of the mechanisms of probiotics regulating immunomodulatory functions is through the activation of TLR’s. For example, one study demonstrated how probiotics can activate innate immunity to “prime adaptive immune response” (Yan & Polk, 2011). A probiotics mixture consisting of L. acidophilus, L. casei, L. reuteri, B. bifidium, and Streptococcus thermophilus stimulated regulatory dendritic cells that express high levels of certain cytokines (such as IL-10, TGF-β, COX-2, and indoleamine 2,3-dioxygenase) to active mechanisms to increase the suppressor activity of CD4CD25 T regulatory cells. In addition, this probiotic mixture induced both T-cell and B-cell “hyporesponsiveness” and downregulated T helper (Th) 1, Th2, and Th17 cytokines without inducing programmed cell death (apoptosis).
Intestinal Epithelial Cells
Probiotics can repair damaged epithelial barrier while producing antibacterial substances and protective proteins, as well as regulate intestinal epithelial immune function (such as cytokine production) (Yan & Polk, 2011). “Many of these responses result from probiotic stimulation of specific intracellular signaling pathways in the epithelial cells” (Yan & Polk, 2011). For example, l. johnonsii has the ability to upregulate TLR7 and TLR9, which may indicate that the probiotic is able to stimulate the gut immunity. “These findings suggest that probiotics regulation of innate immunity in intestinal epithelial cells may serve as a mechanism for disease prevention and treatment” (Yan & Polk, 2011).
Although most of the effects of probiotics are beneficial, several negative effects should be considered before therapeutic application. The biggest concern is within the immune-compromised patients, as there is a risk of sepsis, bacteriemia and fungemia. Probiotic therapy should be discussed with the patient’s medical practitioner.
American Society for Microbiology. (2016, September 6). Missing Microbes with Dr. Martin Blaser. Retrieved 2018, May 4 from https://www.youtube.com/watch?v=KwK_O0ahDKo
Environmedica. (n.d.). Probiotics for Immune System Support. Retrieved 2018, May 3 from https://www.enviromedica.com/probiotics-immune-system
Mallappa, R. H., Rokana, N., Duary, R. K., Panwar, H., Batish, V. K., & Grover, S. (2012). Management of metabolic syndrome through probiotic and prebiotic interventions. Indian J Endocrinol Metab, 16(1), 20-27. doi:10.4103/2230-8210.91178
Vieira, A. T., Teixeira, M. M., & Martins, F. S. (2013). The role of probiotics and prebiotics in inducing gut immunity. Front Immunol, 4, 445. doi:10.3389/fimmu.2013.00445
Yan, F., & Polk, D. B. (2011). Probiotics and immune health. Curr Opin Gastroenterol, 27(6), 496-501. doi:10.1097/MOG.0b013e32834baa4d
Zhou, L., & Foster, J. A. (2015). Psychobiotics and the gut-brain axis: in the pursuit of happiness. Neuropsychiatr Dis Treat, 11, 715-723. doi:10.2147/ndt.S61997