Dr. Justin Sonnenburg

Yeah, there's a big field that's emerging now that we refer to as kind of reprogramming the gut microbiome.

And the issue that I think we're seeing in the field is that...

microbiomes quite often, whether they're diseased or healthy, exist in stable states.

They kind of tend towards this well that has gravity to it in a way, biological gravity, where it's really hard to dislodge that community from that state.

So even individuals, for instance, that get antibiotics

You take oral antibiotics, the community takes this huge hit.

We know that a bunch of microbes die, the composition changes, and that represents a period of vulnerability where pathogens can come in and take over and cause disease.

But if that doesn't happen, the microbiota kind of works its way back to something that is not exactly like, but similar to the pre-antibiotic treatment.

We know with dietary perturbations,

quite often you'll see a really rapid change to the gut microbiome and then this it's almost like a memory where it snaps back to this something that's very similar to the original state even though the diet remains different and so there's this incredible what we refer to as resilience of the gut microbiome and and resistance to change or at least resistance to establishing a new stable state

So that doesn't mean it's hopeless to change an unhealthy microbiome to a healthy microbiome, but it does mean that we need to think carefully about restructuring these communities in ways where we can achieve a new stable state that will resist the microbial community getting pulled back to that original state.

And one of the kind of simplest and nicest examples of this is an experiment that we performed with mice, where we're feeding mice a normal mouse diet, a lot of nutrients there for the gut microbiota, things like dietary fiber.

And we switched those mice, half the mice, to a low fiber diet.

And we were basically asking the question that, you know, if you switch to kind of a Western-like diet, a low fiber, higher fat diet, what happens to the gut microbiota?

And we saw the microbiota change, it lost diversity.

It was very similar to what we see in the difference between industrialized and traditional populations.

But when we brought back a healthy diet, a lot of the microbes returned, you know, it was fairly, you know, there was this kind of memory where it went back to very similar to its original state.

The difference is that when we put the mice on the low fiber, high fat diet, and then kept them on that for multiple generations, we saw this progressive deterioration over the course of generations where by the fourth generation, the gut microbiome was a fraction of what it originally was.

Let's say 30% of the species only remained something like 70% of the species had gone extinct or appeared to have gone extinct.

we then put those mice back onto a high fiber diet and we didn't see recovery.