On November 24th 2016, the Gairdner Foundation and the Farncombe Institute at McMaster University (Canada) held a joint symposium, “The Intestinal Microbiome: Beyond Associations and into the Clinic”. The meeting was organized by Dr. Stephen Collins, director of the Farncombe Institute, and Dr. Janet Rossant, President and Scientific Director of the Gairdner Foundation, and featured leading experts in the microbiome field both from McMaster University and internationally renowned research centers. The symposium was well-attended, selling out days prior to the event. Attendees tweeted about the event using the hashtag #GFsymp2016.
“We structured this symposium in such a way that the broad spectrum of host-microbiota interactions would be presented and their potential clinical relevance emphasized,” says Collins. “In addition, we tried to move away from simply associating microbiome profiles with host phenotype and to delve into the functional consequences of microbiota-host interactions.”
The symposium indeed enabled a lively discussion about one of the most important questions stemming from microbiota research: how do we go from association to causality? Establishing how microbiota alterations affect host physiology and immunity is a key step in determining a causative role of the microbiota in disease development or progression. The topics presented at the symposium highlighted emerging research on how microbiota influences host processes within and beyond the gastrointestinal tract, and how it can be exploited for therapeutic benefit. A variety of topics were covered throughout the day: metabolic diseases, asthma and allergic diseases, early development and aging, brain-gut communication, and manipulating the microbiota for disease-modifying therapies. The wide range of topics presented during this one-day symposium highlights the wide range of systems influenced by the gut microbiota.
Unlike most other microbiome-focused meetings this year, this meeting was centered on understanding functionality rather than association in order to strengthen clinical linkages. Brett Finlay, from the University of British Columbia (Canada), showed that cohorts of children from different countries (Canada and Ecuador) who were at risk for asthma development had altered microbiota profiles. However, although the set of microbes between the two cohorts were different, they had similar functional properties. This brings up the question: can we correlate function of the microbiota in early life with asthma risk, to use the microbiota as a predictive tool? This will require more studies on different cohorts, but Finlay showed promising data that could be expanded to investigate other allergic or inflammatory diseases.
Insight into the functional properties of the microbiome can also be gained through culturing techniques. Mike Surette, from the Farncombe Institute at McMaster University (Canada), showed that contrary to common belief, most of the human microbiome can be cultured. Combining culture techniques with molecular methods reveals a greater microbial diversity than molecular methods alone, and can be used for targeted recovery/enrichment of specific bacterial groups. Culturing and enrichment of specific groups allows us to gain more detailed information about the functional diversity and properties of bacterial species. Ultimately, this aids in the investigation of bacterial-host interactions that influence host physiology and immunity.
How to study bacterial-host interactions and their contribution to disease was another widely discussed topic during the symposium. The use of gnotobiotic models was once again identified as a commonly used technique for proof-of-concept studies. When used in the appropriate setting, gnotobiotic models provide mechanistic insight into how microbes contribute to specific immune functions, physiology, or phenotype. Eran Elinav from the Weizmann Institute of Science in Israel highlighted this beautifully during a presentation of his recently published findings in Nature on post-dieting weight regain. He demonstrated that, following dieting of obese mice, an altered functional microbial signature persisted, despite normalization of metabolic functions. Using fecal transplant studies, where the altered microbiota of previously obese mice was transplanted into germ-free mice, he demonstrated that this altered microbiota signature contributes to faster weight regain and metabolic dysfunction following re-exposure to obesity-promoting conditions (i.e. a high-fat diet). This would suggest that the microbiome contributes to accelerated post-dieting weight regain, and may explain the common “yo-yo effect” where many individuals are unable to maintain weight loss following dieting, and instead gain more weight and experience more severe metabolic complications. Moreover, these exciting results suggest that the microbiota could be targeted to help individuals with metabolic disorders, perhaps for long-term weight management strategies.
The symposium was followed by a morning of poster presentations by Farncombe Institute lab members. Individual labs presented posters that represented their research questions and areas of interest, which ranged from host-microbial relationships during pregnancy and early life to how the gut microbiota contributes to altered metabolism and gut motility. Speakers were invited to discuss their research with graduate students and post-docs in the Farncome Institute, encouraging collaboration and networking.