Multiple sclerosis (MS) is an autoimmune neurodegenerative disease targeting the central nervous system with a prevalence of around 2.8 million people globally. The etiopathogenesis of MS is multifactorial and involves environmental factors. Amongst the environmental factors, the gut microbiota is a key player modulating MS. Dietary habits drive the gut microbiome. Thus, dietary shifts change gut microbiome composition, as well as bacterial metabolites and may induce a proinflammatory or anti-inflammatory response. In fact, an isoflavone-rich (ISO) diet was previously shown to reduce the severity of MS in an animal model of experimental autoimmune encephalomyelitis (EAE). However, translation of this concept to clinical trials, where dietary isoflavones may be recommended for MS patients, must have preliminary evidence that providing the isoflavone-rich diet to people with MS (PwMS) who lack phytoestrogen-metabolizing bacteria has beneficial effects. The previous studies of the research group illustrated that the gut microbiota of PwMS resembles the gut microbiota of mice raised without phytoestrogen, a phyto-free diet, and lacking phytoestrogen-metabolizing bacteria. To elucidate the phytoestrogens impact on mice microbiome inflammatory response, and EAE severity, the research group switched the diet of mice raised under a phyto-free (PF) diet to an isoflavone-rich diet. Faecal samples were collected from mice at different time points to evaluate microbiome variation by diet shift. Then, fecal samples were whole genome shotgun sequenced by CosmosID to describe the microbiome composition of samples. Microbiota analysis underlined that the change in diet from one that is ISO to one that is PF reduces beneficial bacteria such as Bifidobacterium species. The variation is not limited to bacterial species. The variation due to the transition from an ISO diet to a PF diet resulted in functional differences in lipopolysaccharide (LPS) biosynthesis pathways. Interestingly, LPS was alone enough to induce anti-inflammatory effects. LPS extracted from the feces of mice fed an ISO diet induced increased production of anti-inflammatory cytokines from bone marrow-derived macrophages relative to faecal-LPS isolated from mice fed a PF diet. Switching from a PF diet to an ISO diet led to reduced EAE severity and mortality. To sum up, the findings illustrated isoflavone-rich diet modulation of LPS biosynthesis of the gut microbiota signalling an anti-inflammatory response and decreasing disease severity, an important insight for MS management. To read more please check the original paper.