Author: Gabrielle Flora, Associate Director, BRC
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Should successful treatments for these various diseases be developed by way of tinkering in the human microbiome, the implications for the future of human health would be vast. The human microbiome is an ecosystem of microorganisms existing symbiotically within the body, filling an environmental niche by performing functions that human cells cannot. These microbiota outnumber human cells 10-1, and recent studies suggest a potentially powerful impact of these organisms on health.
In recent years, it has become evident that understanding and influencing our microbiomes and the microbiota within them can prevent and protect against diseases and their harmful effects. Some studies even suggest that understanding and exploiting the ecosystem of microbiota within us can function as supplementary treatment for disease. On September 24, 2015, the BioPharma Research Council (BRC) hosted Altering the Microbiome: Can it Impact Health?, a conference designed to explore these relationships at the National Cancer Institute (NCI) in Frederick, Maryland.
“Strategies to manipulate the microbiome are really just emerging,” says Linda Duffy, Ph.D., MPH, Scientific Chair at the Trans-NIH Probiotics and Microbiome Special Interest Group (SIG). Her keynote address, Overview of Progress and Challenges in Probiotic/Prebiotic and Microbiome Research: NIH and Beyond, kicked off the day long symposium. “We’re producing really promising areas of research,” she continues.
Dr. Duffy’s presentation focuses on the potential impact of probiotics and prebiotics on microbiome health. Probiotics are live microbes that are being used in manipulation therapies. “Mechanisms of probiotic action, really in the context of the microbiome, are being examined in all the organ systems,” she says, “and in the gastrointestinal tract using both in vitro and animal models, research is being done on remodeling of microbial communities, suppression of pathogens, suppression of proinflammatory factors, effects on epithelial cell differentiation, and proliferation and promotion of intestinal barrier function. Prebiotics are considered indigestible substrates for the colon, substrates that are widely researched. Certainly [research] approaches with probiotics on the microbiome is one of the most promising areas. Modulation of gut microbial metabolic function using pro and prebiotics and symbiotic avenues have these multi-compartmental connections. It allows us to take body fluid and tissue and to look at it in multidimensional ways,” she says.
Dr. Duffy’s research in probiotics and prebiotics is only one area where understanding the role of the microbiome and its influence on human health is vital. In the past few years, there has been a burst of microbiome research, including disease specific research, therapeutic research, and more.
“With the genomic revolution we now have 25 genomes that are completed and another hundred that are nearly complete… We can now look at the genomic interactions in the gut,” Duffy says, which is a contributing factor to the recent escalated interest in microbiome exploration.
One important area of such inquiry currently taking place focuses on fetal and newborn microbiome development and the interaction between the maternal and infant microbiomes. Prominent researchers exchanged ideas on this extensive topic during a panel discussion moderated by Camilia Martin, M.D., M.S., Director of the Neonatal Intensive Care Unit at Beth Israel Deaconess Medical Center. The panel, The Maternal-Fetal Microbiome: Implications for Maternal and Infant Health, highlighted studies from: Elizabeth Corwin, RN, Ph.D., from Emory University School of Nursing presenting Biobehavioral Determinants of the Microbiome and Preterm Birth in African American Women; Juliette Madan, M.D., M.S., from the Geisel School of Medicine at Dartmouth presenting The Neonatal Microbiome: Exposures and Outcomes; and Amanda Prince, Ph.D., from Baylor College of Medicine presenting We are What we eat: True for Babies?
There is much still to learn about the relationship between fetal and maternal microbiomes. Suchi Hourigan, M.D., Director of Microbiome Research for Inova Translational Medicine Institute presented research focusing on infant development and how to influence it using fecal microbiota transplantation in her talk: Fecal Microbiota Transplantation (FMT): Promises and Pitfalls. Understanding FMT and how it impacts fetal development is important for understanding development of infant health.
While manipulation of the microbiome can produce positive overall effects on our health, maintaining the health of our microbiome is also important. Denise Morais da Fonseca, Ph.D., Researcher for the Laboratory of Parasitic Diseases at NIAID/NIH-Bethesda, brought to light the importance of understanding microbiota in relation to infections during her talk: Microbiota Dependent Consequences of Infections.
The lasting impact of microbiome health on human organ systems was made evident through two talks: Emmanuel Mongodin, Ph.D., from the Institute for Genome Sciences in the University of Maryland School of Medicine presenting The Gut Microbiota Regulates Murine Cardiac Transplant Outcome; and Barbara Methe, Ph.D., from the J. Craig Venter Institute (JCVI) presenting Studies of the Respiratory Microbiome.
“The real question is, are we going to be able to manipulate long term some of the more chronic and difficult to treat diseases with the microbiome?” asks Robert Britton, Ph.D., from the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine. He discussed various implications for disease prevention and treatment due to microbiome research during his talk, Next-Generation Microbial Therapeutics for Prevention and Treatment of Disease. “Unless you’ve been living under a rock you probably know that Fecal Microbiota Transplantation (FMT) is a successful way to treat clostridium difficile. The example I give today is recurring C. diff. but it really could be any disease. FMT is being used currently to treat Irritable Bowel Disease (IBD), other trials for obesity, and type II diabetes.
“I think another thing that’s going to come up is that a lot of the bacteria that are really important members of our intestinal microbiota also are recognized by physicians as opportunistic pathogens,” Dr. Britton continues. “The fact of the matter is that most of the time the only reason they’re bad is because they get to parts of the body they’re not supposed to get to. I would actually say that if you exclude everything that’s in the gut like that from probiotics we’re gonna be missing some key members and key opportunities for research.
“I think that these are really important questions to answer. They’re not easy to answer, but we’re going to have to figure out ways to approach them so that we can get more into research and minimize the risk on this end,” Dr. Britton says. Clearly, disease prevention research is a promising area for microbiome research in the coming years. Understanding the causal relationships between diseases and the ecosystem of microbes within us may well be the solution to solving problems surrounding stubborn diseases.
There is hope, even, in protection against HIV through manipulation of the microbiome. Several promising studies shed light on the potential to create HIV resistant microbiomes. In her talk, Modifying the Vaginal Microbiome to Protect Against HIV, Laurel Lagenaur, Ph.D. discussed the implications of preventative medicine through manipulation of the microbiome. She is the Director of Research at OSEL and a Guest Researcher at NCI. Treatment for HIV positive patients via fecal transplantation is a research area that also shows promise. Stanley Langevin, Ph.D., from the University of Washington, discussed this in his talk Fecal Microbiota Transplantation as a Therapeutic for HIV Associated Gut Dysbiosis.
The conference concluded with the panel: Addressing Microbiome Data Generation and Analysis, moderated by Winston Kuo, DMSc, then Chief Operating Officer for IES Diagnostics and now President at Predicine Holdings Ltd. There is a clear need for more access and sharing of microbiome data globally. Amiran Dzutsev M.D., Ph.D., and Rashmi Sinha, Ph.D., both from NCI, gave presentations highlighting their individual areas of research, taking care to give the audience an impression of how they collect and evaluate their findings.
Interest in the human microbiome grows each year as it becomes clearer and clearer that understanding the human microbiome may be the key to new long-term health plans. “Can the microbiome help health? And I would argue that the answer is clearly yes,” said Dr. Britton, and as it turns out, altering the microbiome truly can impact health. The evidence presented during this conference surely supports that assertion.