Neuro-Immuno-Gastroenterology by Cris Constantinescu Razvan Arsenescu & Violeta Arsenescu

Author:Cris Constantinescu, Razvan Arsenescu & Violeta Arsenescu
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

Nutrient Effect on Gut-Brain Inflammatory Axis

The nutrient effect on central nervous system (CNS) function has been shown to be either direct via metabolites generated during digestion or indirect through complex interaction with gut microbiota and the gut-associated lymphatic tissue (GALT) (Fig. 8.1).

Dietary Metabolites: CNS Pathway

The blood-brain barrier assures selective transport of various dietary-derived compounds that circulate in the plasma. In general, the ability to diffuse across the barrier is a function of the lipid solubility, but molecules with low solubility will benefit from a carrier-mediated transport. Furthermore, vitamins and essential amino acids are not synthesized in the brain and require specific transport systems; their availability in the brain is dependent on the diet and could be limited by substrate competition [17].

Western diet has been associated with obesity epidemic and a rising incidence of autoimmune disorders [18]. Saturated fat has been linked to the development of MS [19] and restriction of animal fat may alter the disease course. The relative concentration of dietary polyunsaturated fatty acids (PUFA) can alter the outcome of chronic inflammation. N-3 fatty acids are found in plant oils (i.e., α-linolenic acid) and fish oils (i.e., EPA and DHA) and exert anti-inflammatory activity. On the other hand, excess of n-6 fatty acids (i.e., linoleic acid) may promote an inflammatory milieu by stimulating the production of arachidonic acid (AA) and downstream production of pro-inflammatory prostaglandins, leukotrienes, and thromboxanes. N-3 fatty acid-derived resolvins D1 and E1 can decrease microglial production of TNFα and IL-6 and, thus, mitigate neuroinflammatory conditions [20]. In an animal model of cuprizone-induced demyelination, n-3 PUFAs docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids were able to reduce the neurodegenerative process and improve motor and cognitive functions [21]. Mechanistically, this was linked to decreased microglial production of interferon gamma (IFNγ), increased myelin phagocytosis, and a shift toward M2 phenotype. Similar protective activity was observed in vascular neurodegenerative disease models [22]. Several randomized control studies have addressed the role of n-3 PUFAs (EPA and DHA) in patients with multiple sclerosis [23, 24]. Until now, there was no significant effect on MRI disease activity, rate, or severity of relapses. All studies used comparable daily doses of EPA and DHA.

Molecular mimicry between host and microbial components may lead to pathological activation of the immune system. A study in children with central nervous system (CNS) inflammatory demyelination revealed autoreactive T cells, as well as abnormal T cell responses against multiple cow-milk proteins [25], such as butyrophilin (BTN). Interestingly, butyrophilin resembles the MS autoantigen, myelin oligodendrocyte glycoprotein (MOG). In a rat model of EAE, BTN administration resulted in accumulation of meningeal and perivascular infiltrates of T cells and macrophages throughout the brain [26]. Furthermore, MOG-specific T cells that were activated by exposure to BTN or/and transfer of BTN-induced T cells, reacted to MOG antigen, thus proving the molecular mimicry mechanism. Based on clinical and preclinical studies, MS patients may choose to refrain from consuming cow’s milk, a rich source of BTN. On the other hand, this cross-reactivity with the MS-putative antigen may be exploited

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