Earlier this month, Dr. Kristina Martinez gave a wonderful talk as part of our C2ST Speakeasy series on the bacteria that live in our gut and how they might affect us. I caught up with her afterwards for some follow-up questions.
C2ST: What do you think was the most important takeaway message from your talk?
Dr. Kristina Martinez: I would say the most important takeaway overall is the concept that what we eat – our diet on a daily basis – has a profound impact on the abundance and the type of bacteria we are harboring in our gut and these microbes directly influence our metabolism and our propensity to gain weight on certain diets.
C2ST: There is this association between health and certain profiles of gut bacteria. The direction of influence is presumed to be that the gut microbiota influences health, as opposed to the other way around. How do we know that this direction of influence is correct?
KM: That’s a really good question, and remains an area of focus – the chicken or the egg question. Is the gut microbiota affecting us, or are we are affecting it? I think it definitely appears to go both ways. I think that there is interaction between the microbes affecting the homeostasis and vice versa. One way we can study this is by using the germ-free mice. Using these mice lacking their own microorganisms, you can transfer microbial communities under certain homeostatic pressures – i.e. following high fat feeding or under disease states – and the recipient mouse will often mimic the phenotype of the donor mouse. This is one indication that the microbes are influenced by the host (shaped by the donor) and can subsequently influence the host (in this case the recipient mouse).
C2ST: Last month we had a speaker who was talking about drug addiction, and she speculated that the gut microbiota might be involved in addiction somehow that we have yet to discover. There have been other connections made between the gut microbiota and other psychological conditions. You mentioned Alzheimer’s and autism spectrum disorder in your talk, and other studies have looked at anxiety and PANDAS syndrome. People have been making a lot of hay over this in the media and such, and I wonder if you could comment on how good the evidence is for this link between the mind and the gut, and if you have any idea how that might work.
KM: I think most evidence relating the gut microbiota to the brain is very new, and there will likely be a lot more work to come in regards to Alzheimer’s and autism. There is actually a post-doc in our lab here [at UChicago] who studies the relationship between the gut microbiota and the circadian rhythm – the sleep-wake cycles. There is definitely a strong connection here, at least from animal studies that have been done, that show the bacteria in the gut influence brain gene expression that regulates sleep-wake cycles as well as metabolism. I think overall this research that is coming out between microbiota and behavior is very new and there is a lot more to be learned in this area than is currently understand based on the current literature. As far as an actual mechanism for linking the two, I think one thing that is really big in the field is the study of metabolomics or wide-scale profiling of metabolites. The byproducts of the bacterial metabolism, small molecules, are thought to circulate the blood stream – some can even cross the blood-brain barrier having a direct impact on the brain. So that is one way in which this connection is being investigated.
C2ST: I’ve heard some people speculate that the vagus nerve might also be a mechanism for this interaction.
KM: That has definitely been suggested as well. There could certainly be an impact of these metabolites on the enteric nervous system – the nerves that innervate our intestines – that signal through the vagal nerves and communicate with the brain.
C2ST: There appears to be mounting evidence, as you mentioned in your talk, for the utility of fecal microbiota transplant (FMT) having therapeutic uses, particularly in the treatment of Clostridium difficile infection. It is my understanding that this hasn’t yet gained mainstream traction among physicians. Why do you think this hasn’t been used more widely?
KM: As you can imagine, there are certainly a lot of concerns in performing FMT based on the donor. Some fears are based upon the donor, could FMT transfer disease for example? The largest challenge is creating standards for treatment – when do you treat, how much to you give, how often do you give it? The process is very involved in terms of screening the donors to make sure they don’t have any type of disease or virus that could be transferred to the recipient. As a result, some FMT donors are family or friends, people who the recipient knows and trusts. Regardless of these challenges, FMT is one of the most effective treatments for antibiotic-resistant C. diff and is becoming increasingly popular, at least with some physicians.
C2ST: Do you think doctors are being overly cautious, or do you support their caution?
KM: I support it, but I think the more it’s done and the more evidence we have showing its effectiveness will drive its use. But we’ll see.
C2ST: Given what we know about the gut microbiota so far, is there any way that we can use that information to improve our health or well-being in ways aside from FMT, or has research not progressed that far yet?
KM: I think better understanding intestinal bacteria in general and how we can target specific types and improve their growth through the use of prebiotics, will allow us to find ways to help promote a healthier microbiota without having to go to extreme measures such as FMT. But I think that FMT is probably necessary for some conditions, such as C. diff infection or colitis, for instance, but for general well-being and health, I think the use of pre- and probiotics could provide a safe way for the general public to improve overall health and metabolism.
C2ST: Are there any ongoing or upcoming studies on the human microbiota that people could volunteer for?
KM: Yes, I think there is actually one coming up here at the University of Chicago led by Alexander Chevronsky’s lab. They are recruiting young men between the ages of 20 and 45. They are taking saliva and stool samples. That is at least one study that is ongoing here.
We are planning a study – also in male participants – that is being coordinated through a local clinical research organization. We are going to be looking at specific prebiotics. I think that they have started their recruitment. It won’t be very many subjects, but it is one study that is upcoming.
C2ST: Is there anything you didn’t get to talk about during your talk that you want to mention?
KM: Well one thing I didn’t mention in my talk is the link between the gut microbiota and the circadian rhythm. I think it’s a fascinating topic and also related to metabolism. A paper came out just last year by my colleague, Dr. Vanessa Leone, published in Cell, Host, and Microbe. I would highly recommend taking a look at that article. She found that the bacteria in the gut have their own circadian behavior apart from the host.
Leone, V., S.M. Gibbons, K. Martinez, A.L. Hutchison, E.Y. Huang, C.M. Cham, J.F. Pierre, A.F. Heneghan, A. Nadimpalli, N. Hubert, E. Zale, Y. Wang, Y. Huang, B. Theriault, A.R. Dinner, M.W. Musch, K.A. Kudsk, B.J. Prendergast, J.A. Gilbert, and E.B. Chang, Effects of Diurnal Variation of Gut Microbes and High-Fat Feeding on Host Circadian Clock Function and Metabolism. Cell Host Microbe, 2015.