COMMENTARY

The Microbiome: 5 Questions Answered

Digestive Disease Week (DDW) 2019

Alok S. Patel, MD; Colleen R. Kelly, MD

Disclosures

July 30, 2019

This transcript has been edited for clarity.

Alok S. Patel, MD: Hello. I'm Dr Alok Patel with Medscape. We're here at Digestive Disease Week (DDW) 2019. I'm honored to be with Dr Colleen Kelly, an associate professor and gastroenterologist at Brown University School of Medicine.

We asked our followers on Instagram to send us questions about the gut microbiome for Dr Kelly to answer. One question that a lot of people asked is, how does the gut microbiome affect mental health?

Colleen R. Kelly, MD: We've known for a long time that there is the gut-brain axis, which allows for communication between our gut and our brain. The mechanism by which this works is that bacteria can produce neurotransmitters (eg, gamma-aminobutyric acid, serotonin) that are active and can cross into the circulation, sometimes through a "leaky gut" inflamed state that can occur. Once in circulation, they can cross the blood-brain barrier and affect cognition. Some of those substances that affect brain function can also come straight up through the vagus nerve.

There is an abstract here at DDW looking at the effect of manipulating gut bacteria in children who are autistic, and whether some of their gastrointestinal and behavioral manifestations can be improved by altering those bacteria.[1]

Patel: So we really can do this. Now a question many people ask all the time is, how do drugs and medications affect your gut microbiome?

Kelly: That is an emerging hot topic. We know that antibiotics affect the microbiome, but we're starting to learn that other medications you wouldn't even expect can profoundly affect certain bacteria, including things that we take all the time, like proton pump inhibitors, nonsteroidal anti-inflammatory drugs, and even metformin in diabetes. It's important to keep this in mind that these different medications we're taking might have unexpected effects.

On the other side of it are patients with cancer who are undergoing chemotherapy. We are starting to learn that their microbiome profiles and the different bacteria that are present can impact the pharmacokinetics of the chemotherapeutic drugs and influence their likelihood of having an adverse reaction or even the therapeutic potential of that drug. So we're talking about perhaps entering into an era of personalized medicine in chemotherapy.

Patel: Speaking of personalized medicine, people are also asking whether taking probiotics can help with their own various conditions. Is this something that people can really do to help their gut microbiome?

Kelly: There is extremely limited evidence on probiotics in any condition. There is a little bit of evidence in irritable bowel syndrome and some in children for the prevention of antibiotic-associated diarrhea. We have to remember that most probiotics are not tightly regulated by the US Food and Drug Administration. You cannot be certain, for example, that the expensive $50 bottle you're getting in the refrigerated section of Whole Foods is any better than a generic brand at the drugstore. I encourage patients to stick to the bigger-name brands. However, I don't recommend probiotics in general for people who are healthy just to maintain health; I don't think we have data for that. We're even starting to have conflicting data in adults as to whether probiotics can prevent C difficile infection, which we always assumed it could, but that may not necessarily be the case. So it's a "buyer beware" situation with probiotics. You shouldn't spend too much money, because a lot more research still needs to be done.

Patel: Let's move on a bit more with the microbiome and talk about fecal microbiota transplantation (FMT). What are some of the risks and cautionary tales about FMT in this early stage?

Kelly: FMT is now widely accepted as the most effective therapy for recurrent C difficile infection. You take stool from a healthy donor, put it into a recipient, and over 90% of the time you can cure that very devastating condition. But obviously, there's a risk of transmission of infections. You have to be very careful with your donor screening and only pick those who are healthy, are living clean lives, and don't have any risk factors for disease transmission. Then you're testing your donors very thoroughly for underlying infections that they may harbor. But we can mitigate that risk by really careful donor selection.

The thing that gets people really nervous are the unknowns regarding long-term risks. Are there things that, maybe way down the line, can occur as a result of manipulating those gut bacteria? They may be at risk for chronic conditions in the future like inflammatory bowel disease or obesity. At the American Gastroenterological Association, we have spearheaded a national FMT registry where we're going to follow up to 4000 patients for 10 years after their fecal transplant to see if there are potentially unknown, long-term effects that we haven't really considered.

Patel: We're certainly doing our due diligence there. But what about the bright future for FMT?

Kelly: One thing that I've seen that's really exciting is that the medical community has really embraced FMT as a treatment for C difficile. Because we see this efficacy, we're not letting patients go through multiple recurrences of C difficile before referring them for an FMT, and I think that's great. Obviously, it's a little difficult to administer in its current form as whole stool from donors. To help us along with that, we have stool banks to identify those good donors. We also have some commercial formulations that are in clinical trials, such as encapsulated forms, that might make it a lot easier for patients to get and their insurance to cover.

The other thing that's really exciting are the emerging applications. We know it works really well for C difficile, so the question is, can it work well for other conditions associated with dysbiosis or altered gut bacteria? I think the next most exciting area is ulcerative colitis. There have now been four clinical trials[2,3,4,5] that have all shown very similar results in mild to moderate ulcerative colitis, with FMT leading to remission rates of up to 30%.

Patel: So when it comes to the gut microbiome and FMT, the future looks bright. Dr Kelly, thank you so much for taking the time to answer these questions.

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