Dietary Isoflavones alter gut microbiota and lipopolysaccharide biosynthesis to reduce inflammation

The etiopathogenesis of multiple sclerosis is strongly affected by the environmental factors such as gut microbiota. Isoflavone diet has been previously shown to reduce severity of multiple sclerosis in animal model EAE. However, the question of how the change of diet to isoflavones in people with MS (PwMS) alters the existing microbiota and may alter MS phenotypic outcome remains obscure. As PwMS gut microbiota resembles gut microbiota of mice raised under phyto-free diet, we utilized the animal model of MS, EAE, and changed the diet of mice raised under phyto-free diet to isoflavone diet to investigate the effects on microbiota and its severity on EAE. Microbiota analysis showed that change in diet from isoflavone to phyto-free reduces beneficial bacteria such as Bifidobacterium species. The alteration of gut microbiota composition was observed along with differences in lipopolysaccharide biosynthesis pathways functionally. Moreover, lipopolysaccharides (LPS) extracted from feces of isoflavone fed mice was able to induce anti-inflammatory cytokine production from the bone marrow derived macrophages. Eventually, mice in which diet was switched from phyto-free to isoflavones exhibited reduced EAE severity and mortality. Overall, our data shows a alternative mechanism of change in LPS biosynthesis by the gut bacteria after diet switch to isoflavones to impart anti-inflammatory response in the gut and affect CNS autoimmunity.