Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation.

The etiopathogenesis of multiple sclerosis (MS) is strongly affected by environmental factors such as diet and the gut microbiota. An isoflavone-rich (ISO) diet was previously shown to reduce the severity of MS in the animal model experimental autoimmune encephalomyelitis (EAE). Translation of this concept to clinical trial where dietary isoflavones may be recommended for MS patients will require preliminary evidence that providing the isoflavone-rich diet to people with MS (PwMS) who lack phytoestrogen-metabolizing bacteria has beneficial effects. We have previously shown that the gut microbiota of PwMS resembles the gut microbiota of mice raised under a phytoestrogen-free (phyto-free) diet in that it lacks phytoestrogen-metabolizing bacteria. To investigate the effects of phytoestrogens on the microbiota inflammatory response and EAE disease severity we switched the diet of mice raised under a phyto-free (PF) diet to an isoflavone-rich diet. Microbiota analysis showed that the change in diet from one that is ISO to one that is PF reduces beneficial bacteria such as Bifidobacterium species. In addition we observed functional differences in lipopolysaccharide (LPS) biosynthesis pathways. Moreover LPS extracted from feces of mice fed an ISO diet induced increased production of anti-inflammatory cytokines from bone marrow-derived macrophages relative to fecal-LPS isolated from mice fed a PF diet. Eventually mice whose diet was switched from a PF diet to an ISO diet trended toward reduced EAE severity and mortality. Overall we show that an isoflavone-rich diet specifically modulates LPS biosynthesis of the gut microbiota imparts an anti-inflammatory response and decreases disease severity.

The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.