Is a healthy and stable gut microbiome difficult or impossible to restore among the following types of patients: 1) types of individuals in the study that you mentioned in which three or more generations on a low-fiber diet led to permanent loss of key microbes; 2) individuals who had never been colonized (normally those born via C-section are formula-fed); 3) individuals whose mucosal microbiome and immune system vigilantly exclude newcomers resulting in unsuccessful colonization of probiotics?

Great question. Really good question. I think the way to think about this is to kind of zoom out and say, “There are many different factors that influence the health of our microbiome,” and you’ve named a few, and then we could also add, “The more environmental factors that are under our control like the quality of our diet—stress is huge for the microbiome, exercise has a big impact, our intake of microbiota-accessible carbohydrate, aka fiber, avoiding medications that disrupt the microbiome as much as possible like antibiotics, which most people know about, but there are also many others like NSAIDs [nonsteroidal anti-inflammatory drugs], birth control.” I have a whole article about this that we can probably find and put in the chat section. Think of it this way, like, the more of those factors that are off, the more likely that the microbiome will be disrupted, and the more of those factors that are aligned and in the right place, the more likely it will be that you’ll be able to build or rebuild a healthy microbiome. Now, it doesn’t mean that someone who’s had every one of those factors perfect will have the highest likelihood of having an optimal microbiome. So, maybe a hunter–gatherer, for example. Someone who maybe has a few [of] those factors working against them, though, still has a good chance to have a healthy microbiome if they’re doing everything right. They may never have the super optimal microbiome that somebody like a hunter–gatherer living in a pristine environment would, but unfortunately, none of us fall into that category living in the industrial world. It’s really kind of a case of having to do the best you can and trying to work at this to influence the things that we do have control over and trying not to sweat too much [about] the rest of it. That’s, I think, a good way to support our patients.