Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria, 2021, Samantha N Jensen et al

That's an interesting study @Mij, thanks for posting.

 

That study was on mice forced to swim, not on ME/CFS. I don't think that's a valid model.

 

While I think pwChronicIllness need more of certain compounds than others to alleviate the extra stress put on the system by illness, I find it unlikely that patients have a markedly lower isoflavone content in their diet than healthy controls.
This quote from the background

makes me wonder if increasing isoflavone intake alone would be enough, the bacteria would have to be introduced first. And there are more things that influence which bacteria is able to colonize the gut than one single compound alone.

Edit: I would have liked to see the data of mice fed normal chow in the plots, mice chow usually contains soy which would be a source of isoflavones although likely less than the isoflavone enriched diet.

 

The study said the same thing - the normal feed had a level of isoflavones that was between the levels of the isoflavone-free and high-isoflavone diets:

They do some studies on this too. They found that an isoflavone diet changed the abundance of certain gut bacteria and the differences between the mice on the two different diets correlated with some of the differences found between people with MS and healthy controls. They do note that a suitable diet and a suitable microflora are required.

They wiped out the gut bacteria of the mice with a broad spectrum antibiotic and replaced it with specific bacteria. The mice with the bacteria thought to be protective had much milder illnesses when the EAE was subsequently induced provided they had isoflavones in their diet. The mice needed to have both the isoflavones in the food and the good bacteria in the gut.



Next, they tested a metabolite produced by the protective bacteria:

A sustained intake of the metabolite, Equol, gave the same protection as a high isoflavone diet + bacteria (see the left hand chart).

It's about now I start to get suspicious that this team has shares in a company manufacturing Equol tablets.... Still, it's interesting. Not least because these people and others seem so convinced that they can make mice get something like multiple sclerosis. And because it suggests that frequent dosing of antibiotics might be a contributory factor.

 

It's good they write it as many are unaware of what the mice are regularly fed, which is problematic when extrapolating to what humans eat. The reason I wanted the normal chow mice data included in the other plots is because we see different prevalences of illnesses between people who move from countries with low to high prevalence, and this is believed to be due to among other things lifestyle. While some dietary change occurs when people move from one country to another, they also often eat food that is part of the diet of the contry they came from, though maybe not in the same amount. The normal chow might have a more realistic level of isoflavones than the high isoflavone diet (though there are other problems with regular chow that makes it unsuitable as a stand-in for "a regular diet").

I missed the part where they used the antibiotic.

While isoflavones are not a large component in the diet in many countries with high prevalence of MS, we have other flavones that are beneficial for gut health and also show antiinflammatory properties (which, as with the isoflavones in this study, have been linked to the microbiome).

I really dislike this focus on a single component and/or food. It is typically something that is easy to isolate and that can be turned into a supplement to use in a study (and I guess potentially sold). I'd be more interested if similar effects can be seen with a whole food diet that includes different flavones (but each with likely lower amounts than what is used here).

You can give mice (and humans) carrageenan and it will cause/worsen gut inflammation in suceptible individuals, causing relapse of inflammatory bowel disease. In both cases as soon as integrity of the gut wall is part of the equation vitamin D status is important (which is also associated with MS prevalence), though I'm not sure what threshold would be relevant here as most studies are done on cell lines (and observational studies on human health and vitamin D, with their own issues such as using different threshold for deficien/sufficient vitamin D status). At high enough levels vitamin D protects barrier integrity by increasing expression and/or improving localisation of tight junction proteins. Additionally other nutrients such as vitamin A, zinc and glutamine are beneficial. Other compounds (not just flavones) that can make bacteria create beneficial compounds such as short chain fatty acids... there are more "stressors" in the gut of people who eat diets than mice that get standarized chow.

A very good question. Looking at single compounds in mice where one can control the rest of the diet (and environment) more or less 100% is not something that can be easily translated to humans.