Commensal gut flora and brain autoimmunity: a love or hate affair?

Abstract

Multiple sclerosis (MS) and other chronic inflammatory autoimmune diseases represent major public health challenges in industrialised Western society. MS results from an autoimmune attack against myelin structures by self-reactive lymphocytes, which are normal components of the healthy immune repertoire. The nature of the triggers that convert the innocuous self-reactive lymphocytes into an autoaggressive phenotype is poorly understood. In the past, it was primarily suspected that pathogenic infections trigger MS. However, so far, none of the incriminated pathogenic microbes were firmly associated with the disease. A growing body of evidence in animal models of MS implicates the gut microbiota in the induction of central nervous system (CNS) autoimmunity. The mammalian gut harbors a diverse population of microbial organisms which are essential for our well being. There is an increasing understanding that the gut microbiota not only modulates the local immune functions but also affects the systemic immune system. We are only just beginning to understand the nature of the interactions of the gut microbiota with the host's immune system especially in the context of autoimmune diseases. This review will address the influence of intestinal microbiota on immune homeostasis and on the development of autoimmune responses at sites distal to the intestine with a particular emphasis placed on a discussion about CNS autoimmunity.

TNFR2 Deficiency Acts in Concert with Gut Microbiota To Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease

“…However, no etiologic or causal effect has been firmly established. In contrast, our results are consistent with numerous other more recent studies indicating that commensal, rather than pathogenic, bacteria facilitate CNS autoimmune demyelination (29,30,(66)(67)(68). Attenuated MOG-induced EAE development in antibiotic-treated and germ-free mice has linked gut microbiota to CNS demyelination (29,30).…”

Gut Microbiota and Central Nervous System Condemned to Understand Each Other: Their Role in Multiple Sclerosis

“…14 resident bacteria, which respond to diet, obesity, immune system dysfunction, environmental factors, leaky gut, psychosocial stress, early life stress and drug consumption [3,8,9]. Disbiosis (or disbacteriosis) can be generated by a bad understanding between host and microbiota, and, specifically, between the receptors of the former and the ligands derived from the latter.…”

“…Disbiosis (or disbacteriosis) can be generated by a bad understanding between host and microbiota, and, specifically, between the receptors of the former and the ligands derived from the latter. Any of the metabolites produced by the bacterial flora (fermentation products, neuroactive molecules or bacterial immunostimulators like lipopolysaccharides), could cause immunological or even neuropsychiatric disorders [3]. The capacity of certain bacterial antigens such as lipopolysaccharide A to mediate in the traffic and migration of a population of intestinal antigen-presenting cells to the lymphoid tissue, suggests an important cross-talk between the intestinal mucous and the brain/spinal cord [1].…”

“…Thus, the sterilization of the intestine with antibiotics reduces the severity of EAE [3]. All this is due to the attenuation of the proinflammatory response of the T H 1, T H 17 cells, T-regulating cells, invariant natural killers or T and B cells, whereas colonization by segmented filamentous bacteria (SFB) makes them more sensitive [3].…”

“…Gut microbiota is essential in mammals for the correct development of gut flora and the maturation of the host's immune system, generating a complex and delicate balance called "microbioma", whose alteration triggers a dysregulation of the immune response, which ends up exerting effects on the gut tract and CNS [1,[3][4][5][6][7]. However, the mechanisms on which these effects and relationships are established have not currently been clarified.…”