The role of gut microbiota in immune homeostasis and autoimmunity

Abstract

Keeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body's health. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis. Moreover, it has recently become obvious that alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders. Here we review the advances in our understanding of how the gut microbiota regulates innate and adaptive immune homeostasis, which in turn can affect the development of not only intestinal but also systemic autoimmune diseases. Exploring the interaction of gut microbes and the host immune system will not only allow us to understand the pathogenesis of autoimmune diseases but will also provide us new foundations for the design of novel immuno-or microbebased therapies.

GUT-the Trojan Horse in Remote Organs’ Autoimmunity

“…Multiple animal models of human ADs suggest a direct involvement of the commensal microbiota, when invaded with the pathogenic dysbiota, in disease development. Under germ-free conditions no disease is developing in the animal models of inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis, supporting the notion of "no bags, no disease", while in some others they are only attenuated [16]. Causality is strengthened by the reintroduction of specific pathbiont restoring the AD severity.…”

“…Data is accumulating that intestinal luminal environmental factors might perturbate the regulatory mechanisms of the tight junction, resulting in a leaky gut thus breaking equilibrium between tolerance and immunity to nonself-antigens. Nutrients, toxins, allergens, carcinogens, intestinal infections, dysbiotic bacteria, drugs and stress and the recently described industrial processed food additives, can breach the tight junction integrity [3,4,[7][8][9][10]12,13,[15][16][17][18]23,24,28,29]. In fact, TJ dysfunction seems to be a primary defect in AD [28][29][30].…”

Microbiome and Human Health: Review

“…26 Mikrobiyotanın immün sistem üzerinde, kısa zincirli yağ asitleri gibi çeşitli metabolitlerin üretimini sağlayarak mukus salgılanma-sını artırması, REGIIIγ ve REGIIIβ gibi antimikrobiyal molekülleri üretmesi gibi doğrudan veya dolaylı çeşitli etkileri bulunmaktadır. [27][28][29][30] Örneğin; Bacteroides thetaiotaomicron epitelyal tabakadaki paneth hücrelerini uyararak anjiyogenin üretimini artırır. Böylece barsak submukozal kapiler ağının başlatılmasını sağlar.…”

The Gut Microbiota and Inflammation in Rheumatoid Arthritis

“…Evidences support the existence of immune cross talks between the microbiota-derived products and the gut epithelium that involves molecular exchange of bacterial signals recognized by host receptors to mediate beneicial outcomes for both the microbiome and human beings [42][43][44][45][46][47]. The gut microbiota have the potential to efectively stimulate and direct the host innate and adaptive immune responses in humans by triggering instructional signals to the immune cells, particularly regulatory T (Treg)-cell and T-helper (Th) cell diferentiation.…”

“…SCFAs are actively produced by anaerobic microbiota in the colon as fermentation products of digestion-resistant dietary ibers [46,47]. SCFAs produced locally in the colon are either absorbed and metabolized within the colonocytes or transported into the circulation to reach other organs, such as the liver and muscles.…”