Summary: A diet rich in isoflavones — plant compounds found in legumes such as soybeans, peanuts and chickpeas — reduces multiple sclerosis‑like symptoms in mice, but only when specific gut bacteria that metabolize those compounds are present.
Source: University of Iowa
Researchers at the University of Iowa report that interactions between diet and the gut microbiome can influence multiple sclerosis (MS) in a mouse model.
In a study led by Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa, mice fed a diet high in isoflavones showed protection against MS‑like symptoms. Isoflavones are phytoestrogens — plant-derived compounds that have structural similarity to estrogen — found in foods such as soybeans, peanuts, chickpeas and other legumes. Crucially, the protective effect depended on the presence of gut bacteria capable of converting isoflavones into active metabolites.
Published July 9 in Science Advances, the study links dietary isoflavones, specific isoflavone‑metabolizing bacteria, and a bacterial metabolite called equol to reduced disease severity in an experimental autoimmune encephalomyelitis (EAE) mouse model, which is commonly used to study MS.
Previous human studies have shown that people with MS have different gut microbiomes compared with individuals without MS, and notably lack some bacteria that can metabolize isoflavones. Mangalam and colleagues designed experiments to test whether those bacterial differences might contribute to disease by altering how the body processes dietary isoflavones.
The team compared mice fed an isoflavone‑rich diet with mice fed an isoflavone‑free diet. Mice on the isoflavone diet developed a gut microbiome composition resembling that of healthy human donors and included bacteria known to metabolize isoflavones. Mice on the isoflavone‑free diet developed a microbiome more similar to that observed in patients with MS and lacked these beneficial bacteria.

The protective benefit of the isoflavone diet required the isoflavone‑metabolizing bacteria: when those bacteria were removed from mice on the isoflavone diet, protection against EAE disappeared. Reintroducing the bacteria restored the diet’s protective effect. The researchers also demonstrated that equol, an isoflavone metabolite produced by gut bacteria, can itself reduce disease severity in the mouse model.
Multiple sclerosis is an autoimmune condition in which the immune system attacks the central nervous system, damaging the myelin sheath that surrounds nerve fibers. Symptoms can include muscle weakness, balance and coordination problems, visual disturbances and cognitive difficulties. Treatments exist that slow disease progression, but there is no cure. MS likely arises from a combination of genetic predisposition and environmental triggers, and the gut microbiome has emerged as a potential environmental contributor to disease onset and progression.
Mangalam and his team, including first author Samantha Jensen, a graduate student in immunology, emphasize that their findings provide mechanistic evidence linking dietary components, gut bacteria, and MS‑related inflammation. The study suggests that restoring or supporting isoflavone‑metabolizing bacteria in the gut could be a strategy to support protective effects from an isoflavone‑rich diet.
The research team included UI scientists Shailesh Shahi and Stephanie Peterson; Katherine Gibson‑Corley at Vanderbilt University; Nicole Cady at the University of Michigan; and Arnav Gupta at the KK Birla Institute in Goa. Funding came in part from the National Multiple Sclerosis Society, the National Institute of Allergy and Infectious Diseases, the National Institute of Environmental Health Sciences, and the Roy J. Carver Charitable Trust.
About this diet and multiple sclerosis research news
Source: University of Iowa
Contact: Jennifer Brown – University of Iowa
Image: The image is in the public domain
Original Research: Open access. “Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis” by Ashutosh Mangalam et al., Science Advances
Abstract
Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis
The gut microbiota is a potential environmental factor that influences the development of multiple sclerosis (MS). Previous work has shown distinct differences between the gut microbiomes of patients with MS and healthy individuals, but the relevance of those differences to disease progression was unclear.
Earlier findings indicated that bacteria capable of metabolizing isoflavones are less abundant in MS patients, suggesting these bacteria might have a protective role. Using a mouse model of MS, the current study demonstrates that an isoflavone‑rich diet reduces disease severity in a manner that depends on the presence of isoflavone‑metabolizing bacteria and on their metabolite equol. Mice fed the isoflavone diet developed a gut microbiome composition resembling healthy human donors, while mice on an isoflavone‑free diet developed a microbiome resembling that of patients with MS.
Overall, the findings indicate that diet‑driven changes to the gut microbiome can modulate autoimmune inflammation and may play a role in MS pathogenesis.