This 2021 rodent study investigated effects of dietary isoflavones and gut microbiota:

“Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system (CNS) that results in sensory, motor, and/or cognitive dysfunction. This is due to complex interactions of genetic and environmental factors that trigger activation of autoreactive T cells, leading to subsequent immune cell infiltration into the CNS, neurodegeneration, and axonal damage.

Genetic influences on MS have been well characterized, such as the strong association of certain human leukocyte antigen haplotypes with disease. In contrast, environmental factors – which account for around 70% of disease risk – remain understudied.

In humans, certain gut bacteria digest phytoestrogens, which are plant-based compounds that resemble estrogen. Isoflavones are a major class of phytoestrogens that are highly abundant in legumes such as soy. Humans do not have the necessary enzymes to break down isoflavones, and rely on gut microbiota to harvest these biologically active metabolites.

In the present study, we demonstrate that experimental autoimmune encephalomyelitis (EAE), an animal model for MS, is suppressed in mice fed a diet supplemented with isoflavones.

Adlercreutzia equolifaciens and Parabacteroides distasonis, which metabolize isoflavones, were more abundant in mice on an isoflavone diet. Both genera were enriched in healthy individuals but depleted in patients with MS. Conversely, Akkermansia muciniphila was found in greater abundance in mice on an isoflavone-free diet, and this genus is commonly enriched in patients with MS compared to healthy individuals.

We demonstrate that bacterial therapy with P. distasonis and A. equolifaciens results in markedly different clinical disease scores depending on diet of the host. In the absence of isoflavones, isoflavone-metabolizing bacteria may begin to metabolize host products, such as mucins, resulting in a proinflammatory state.

Considering the interplay between diet and gut bacteria is critical when developing dietary and gut microbiome-based therapies for MS and other diseases.”

https://www.science.org/doi/10.1126/sciadv.abd4595 “Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis”

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Parabacteroides distasonis is my second most abundant gut microbiota species at 11.076%. Its main function is to metabolize carbohydrates, which are the bulk of my diet. Haven’t focused on isoflavones.

If you want to increase isoflavones with a soy product like tofu, try to eat it raw, steamed, or simmered in soup. Broiling, grilling, or sautéing tofu causes a dramatic rise in AGEs.

I came across this study by its citation in Dr. Paul Clayton’s rambling blog post Stranger together.