A new mouse model study at the University of Iowa has found that a diet rich in isoflavone, a phytoestrogen, might protect against multiple sclerosis (MS). The same study team previously found that isoflavone-metabolizing gut bacteria are less abundant in patients with MS.

The present study findings were published in Science Advances and highlight the role of diet and gut microbiome in disease development. 

The team noted that an isoflavone-rich diet suppressed experimental autoimmune encephalitis (EAE) in mice. This was demonstrated by placing female mice on either an isoflavone-rich or isoflavone-free diet for 6 weeks, and then inducing EAE using the myelin oligodendrocyte glycoprotein (MOG) epitope, MOG35-55/CFA. The mice on an isoflavone-free diet showed a severe disease course, whereas EAE was greatly diminished in mice on isoflavone.

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Decreased proinflammatory cellular infiltration was also seen in mice placed on an isoflavone-rich diet. The study found a reduced number of infiltrating CD4+ T cells in the central nervous system (CNS) compared to mice on an isoflavone-free diet 20 days after inducing EAE, consistent with lower disease severity.  

The study findings also suggest that isoflavones promote an immunological environment that is less conducive for autoinflammation through the activation of autoreactive antigen-specific CD4+ T cells. This was shown by the decreased frequency of MOG35-55-specific CD4+ T cells that were also positive for CD44 or Ki67 in mice on an isoflavone-rich diet, and by the slower proliferation of cells in the spleen and draining lymph nodes of those mice. The team has also been able to specify equol, an isoflavone metabolite formed by gut bacteria, as a key to disease protection against MS.

“Interestingly, previous human studies have demonstrated that patients with multiple sclerosis lack these bacteria compared to individuals without MS,” said Ashutosh Mangalam, PhD, study lead and associate professor of pathology at the University of Iowa in Iowa City. He believes that their study findings provide further evidence that isoflavone-rich diets along with isoflavone-metabolizing gut bacteria could serve as a possible treatment for MS.


Jensen SN, Cady NM, Shahi SK, et al. Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis. Sci Adv. 2021;7(28):eabd4595. doi: 10.1126/sciadv.abd4595

A plant-based diet combined with a healthy microbiome may protect against multiple sclerosis. University of Iowa Carver College of Medicine. July 12, 2021. Accessed July 19, 2021.