Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation

Area of Science:

• Microbiome research
• Neuroimmunology
• Nutritional science

Background:

• Environmental factors like diet and gut microbiota significantly influence multiple sclerosis (MS) etiopathogenesis.
• An isoflavone-rich (ISO) diet has previously demonstrated reduced MS severity in the experimental autoimmune encephalomyelitis (EAE) animal model.
• People with MS (PwMS) often lack gut bacteria capable of metabolizing phytoestrogens, similar to mice on a phytoestrogen-free (PF) diet.

Purpose of the Study:

• To investigate the impact of phytoestrogens on gut microbiota, inflammatory responses, and EAE disease severity.
• To determine if switching mice from a PF diet to an ISO diet alters microbiota composition and function.
• To assess the potential of an ISO diet as a therapeutic strategy for MS.

Main Methods:

• Mice previously on a PF diet were switched to an ISO diet.
• Gut microbiota composition and functional pathways (LPS biosynthesis) were analyzed.
• Lipopolysaccharide (LPS) from fecal samples was used to stimulate macrophages in vitro.
• EAE disease severity and mortality were monitored in mice switched to the ISO diet.

Main Results:

• Switching from an ISO to a PF diet decreased beneficial bacteria like *Bifidobacterium* species.
• Dietary changes influenced lipopolysaccharide (LPS) biosynthesis pathways in the gut microbiota.
• Fecal LPS from ISO-fed mice induced greater anti-inflammatory cytokine production compared to PF-fed mice.
• Mice switched to an ISO diet showed a trend towards reduced EAE severity and mortality.

Conclusions:

• An isoflavone-rich diet modulates gut microbiota's LPS biosynthesis.
• This dietary intervention promotes an anti-inflammatory response.
• An ISO diet shows potential in decreasing multiple sclerosis disease severity.