Dr. David Relman on the Past, Present, and Future Potential of Microbiome in Medicine

During the American Society for Microbiology Microbe 2017 New Orleans meeting, Contagion^®​ interviewed David Relman, MD, ASM Microbe 2017 Vice-Chair, Professor in Medicine, and Microbiology & Immunology at Stanford University on microbiome research and its potential utility in medicine.

CONTAGION^®: Where Do You Think The Future of Medicine is Going with the Microbiome-Based Therapies?

DR. RELMAN: This is a hard one to predict given so many uncertainties. First, microbiome research may help with diagnostics and prognostics to find patients at greater risk for developing infections like Clostridium difficile. A second area may be in treatment, but I’m cautious as it is still not so simple. There are a few examples of therapeutically beneficial small molecules made by bacteria that have been identified. The third area is in prevention. It will be possible at some point to sort out what confers stability or resilience on a person that is about to enter hospitalization, take a drug, experience a surgical procedure, or is at risk of some disease condition. An intervention may involve provision of groups of organisms thought to be beneficial, followed by feeding of those organisms to keep them there. It is important to remember that data indicate that it is actually hard to instill an organism and get it to stay. So, we must know how to feed and promote said therapeutic groups of organisms.

C: Can We Get These Organisms Through a Pill, Instead of Insertion From Below?

R: Fecal transfer is being done in a pill, but it turns out you need more organisms to have an effect if you administer it orally than if you administer it rectally, but you need lots of pills, like 20-30 big pills a day, to get past the stomach. Some day we should be able to do this, for sure. There are many companies and researchers trying to sort out the minimum ecosystem needed, eg. 14 different strains for 14 different people. Then, the bacteria have to be fed appropriately or else they will be eliminated by selective advantage. The reason C. difficile transplants work so well is that they are given to the person precisely at the time they are beginning their recovery from a bout with C. difficile colitis. Most significantly, these people have a damaged ecosystem in their gut that is teetering and more vulnerable to elimination. If its left alone, it creates an inflammatory environment that most healthy bacteria cannot tolerate, while C. difficile thrives. So, now that we understand this, the organisms must be fed properly during this time along with antibiotics targeting C. difficile.

C: Can An Individual Also Experience Bacterial Effects From Frozen Vegetables in a "Food as Medicine" Paradigm?

R: Definitely this can help indirectly, in the sense that many fruits and vegetables will properly feed your beneficial organisms by providing fiber, and potentially directly, [by] providing therapeutic beneficial organisms. Freezing does not kill everything—organisms with spores, capsules, or strong cell walls can survive and then thrive. For example, in a study presented at this conference, a small molecule was identified in Lactobacillus that inhibits the growth of antibiotic-resistant organisms. A few years ago, there was a study identifying a small molecule named lactocillin that is made by a different Lactobacillus species that normally lives in the vagina. [The molecule] doesn’t affect healthy bacteria, but it does have potent antibacterial activity against a range of Gram-positive vaginal pathogens.

C: Can You Discuss the Connection Between the Microbiome and Neurodegenerative Disease (as highlighted by Dr. David Perlmutter, MD (Private practice neurologist with over 20 years of experience, fellow of the American Academy of Nutrition, author of The Grain Brain and Brain Maker)?

R: I have followed Dr. Perlmutter’s work. It’s interesting and worthy of further exploration, but I am concerned with the links to a variety of clinical disorders. These are usually associations, not causation studies. Secondly, if there is a link to depression or Parkinson’s Disease for example, it seems likely to be a small contribution, since we already know other factors that are known to be connected. [However,] that doesn’t mean we should not be focusing on it, because it may be one of the things that we can do something about. We cannot typically do anything about a genetic problem, but changes in the microbiome are conceptually simple.

C: Are There Any Vitamins Besides B12 for Which Bacteria are Known to Play a Real Significant Role?

R: Bacteria can process vitamin K. If you take antibiotics, you cannot clot blood as well. It normally doesn’t matter, but if someone is on warfarin/coumadin, if they take an antibiotic, it can kill them. This is likely to be a bigger problem than we are aware. There is a lot of variation in adverse effects of drugs, and also, a lot of variation in people’s vitamin deficiencies.

C: Any There Other Anatomies That are Looked at in Microbiome Research Besides the Gut?

R: The first anatomy of microbiome research focus was the mouth. The most common infectious disease in the United States is, in fact, gum disease or oral cavities, but unfortunately that research community typically publishes in different journals and goes to different meetings. They have a long proud tradition. It is unfortunate that there is not more overlap in the research communities. Other non-gut anatomies of focus in microbiome research include the skin and vagina.

C: What Are the Next Steps for Your Research?

R: We are working on several things. We are generally interested in what makes the microbiome stable and what allows it to recover from a disturbance, like an antibiotic. So, we do a lot of longitudinal studies involving healthy people, where we observe what happens to the microbiome after a colonic clean out, antibiotic, drug, or diet shift. We look at many people and try to find the common features for remaining stable. We are also looking at pregnancy and how that affects gestational outcome. Most significantly we are finding out that there is a certain kind of microbiome that promotes premature labor. Hopefully one day we may help to prevent premature delivery, and instead promote full-term healthy in utero development.

W. Todd Penberthy, PhD is a medical writer with over 4 years of experience based in Orlando, Florida. Prior to that Todd was a professor directing biomedical research using zebrafish models of human disease with expertise in orthomolecular niacin-related science for 10 years.