Jeffrey M. Kaplan, MD: What I was going to discuss with you, Dr Baker, is what is the relationship between the gut microbiota and risk of relapse?
Matthew J. Baker, MD: Oh, that’s a fascinating question. I think, again, in this era of microbial infection, everyone is acutely aware of the microbes around us, on us, and in us. And patients often ask us about the influence of diet on their MS [multiple sclerosis]. What’s fascinating to me is that cell to cell, we are more bacteria than we are ourselves. We live in this mutualistic environment with these gut bacteria. That’s not necessarily a bad thing, but there are certain groups of bacteria that have a tendency to promote a proinflammatory state.
So we see the same sort of cellular response we see in MS—upregulation of proinflammatory T cells, upregulation of inflammatory cytokines, increased gut permeability. We have identified that there is an association with certain populations of bacteria and MS risk. So if you look at MS patients’ gut bacteria, it‘s similar but distinctly different from those who don’t have MS. We also understand that there is a role the gut microbiome plays in protecting and promoting disease.
We don’t know what the risk is or what the influence is of the gut microbiome on disease progression and relapse activity. One way to evaluate this is to look at a population of patients who were relatively pristine.
There’s a collaborative effort looking at pediatric multiple sclerosis. So, these are kids. They have MS. You know where they’ve been. They’ve had a short lifespan. The parents know what they are feeding them. They know what vaccinations they have had. It’s expected they won’t have a lot of other confounding risk factors—diabetes, hypertension, hypercholesterolemia, obesity, etc. So you can kind of make it a pure population.
And so, they took stool samples and they evaluated for 18 or so classes, or orders, of bacteria that are common. They looked at the relative presence or absence of those bacterial orders and then whether they were high or low in abundance.
What they found was that there were 2 orders of bacteria. These are tongue twisters for me, but one of them was pasteurellales and the other was enterobacterales. These seem to be protective in the risk of relapse in this pediatric population. And interestingly, these are the same bacteria that confer benefits in reducing inflammation, or have a more anti-inflammatory behavior, overall.
Jeffrey M. Kaplan, MD: When do you think gut microbiota is formed in a child? At about what age do you think that develops?
Matthew J. Baker, MD: It’s early on, I believe. I think that has some relationship to whether an individual is breastfed. The mother will pass some of the bacteria on to the baby. And even in the birth canal, I think. As the baby is passing through the birth canal, they will acquire some bacteria from mom that then colonizes the gut. So it would be interesting to kind of see MS risk in those patients or in those who develop MS. Were they delivered by C-section? Were they delivered vaginally? So that is some fascinating data. I don’t think we know for sure, or at least I don’t.
Jeffrey M. Kaplan, MD: How does the gut microbiome contribute to MS onset among high-risk populations, such as family members?
Matthew J. Baker, MD: That is such an interesting question. Another way to look at risk of disease onset, or maybe risk of relapse, is to look at those individuals who may be at higher risk for developing MS. We know that if you have a first-degree relative with multiple sclerosis, you’re more likely to develop MS then someone who doesn’t, or has a second or third or fourth degree, and so on, and so forth. So if you evaluate those individuals and look at MS susceptibility risk, you find the usual suspects in the gut microbiome that promote inflammation.
Some of those usual suspects have a role in metabolism of short-chain fatty acid. So there’s this association between diet, gut microbiota, and genetic susceptibility. It’s all really fascinating data, and I think it’s evolving. What we do with that data in the next few years, I think, is going to be important.