Diet and the gut microbiome have emerged as important factors in regulating the pathobiology of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. The Mangalam laboratory has previously shown that individuals with MS have distinct gut microbiota, with a specific depletion of gut bacteria responsible for metabolism of dietary phytoestrogen. The importance of phytoestrogen-metabolizing gut bacteria in preventing MS has been verified by the Mangalam laboratory using a mouse model of the disease (experimental autoimmune encephalomyelitis or EAE), where a diet rich in isoflavone (a type of phytoestrogen) protected from severe disease.
In this new study led by Sudeep Ghimire, a postdoctoral scholar in the laboratory, results demonstrated an isoflavone-rich diet suppresses inflammation in EAE through enrichment of beneficial bacteria and modulating bacterial genes linked with inflammation. The team compared the effects of switching animals from an isoflavone-rich diet to an isoflavone-free diet and vice versa, to determine the feasibility of using a diet-based therapy in the clinic. They found that switching to an isoflavone-free diet led to loss of beneficial bacteria within a week, whereas it took almost 4 weeks for beneficial bacteria to recover after switching to a healthy isoflavone-rich diet. Besides fostering the growth of bacteria with the ability to metabolize isoflavone into equol, an isoflavone rich diet also promoted bacteria with reduced levels of lipopolysaccharide (LPS), a bacterial toxin linked with inflammation. LPS extracted from the feces of mice on an isoflavone-rich diet induced lower levels of inflammatory cytokines when cultured with immune cells in vitro. Importantly, the team was able to show that mice switched from an isoflavone-free diet to an isoflavone-rich diet exhibited reduced disease (EAE).
Taken together, the study strengthens the idea that an isoflavone-rich diet in combination with specific gut microbiota, may provide health benefits and can be potentially used as a therapy for inflammatory diseases such as MS.
The study was supported by the NIH (National Institute of Allergy and Infectious Diseases and the National Institute of Environmental Health Sciences), the VA (Veteran Affair Merit Award), and the Roy J. Carver Charitable Trust.
In addition to Drs. Mangalam and Ghimire, the team included Dr. Shailesh Shahi, Peter Lehman, Stephanie Peterson and Nicole Cady at the University of Iowa and Drs. Faraz Rashid and Shailendra Giri at the Henry Ford Health System, Detroit, MI.
The article can be viewed at:
https://www.tandfonline.com/doi/full/10.1080/19490976.2022.2127446