New frontier of microbiomics generates lots of research buzz

‘it’s just as effective as the common steroid-based treatment but without any of the side effects.’ – Dr. Morgan Langille

Sometimes called the new frontier, microbiomics, the study of the microbiome, is currently about as hot as it gets for any discipline in the sober world of science.

“It’s really exciting,” says Dr. Morgan Langille, the Canada Research Chair in Human Microbiomics at Dalhousie University. “Using next-gen DNA sequencing, we are finally able to profile all of the microbes in and on our bodies, not just the ones we can grow in the lab, and relate those communities of microbes to various diseases.”

Science is just starting to make headway in exploring the human microbiome, the trillions of single cell organisms – bacteria, archaea, eukaryotes and viruses – that form symbiotic communities in the gut, genitals, lungs, sinus and skin. A well-functioning, diversely populated microbiome is now considered vital to maintaining human health. Among other things, the microbiome in the gut, for example, synthesizes vitamins and breaks down food so the body can more easily absorb nutrients.

Microbiomes are also found in animals, plants, soil, and in fresh and salt water. Their pervasiveness has generated widespread researcher interest and projects are typically collaborative and multi-disciplinary.

Langille specializes in bioinformatics, the use of computer algorithms to process and interpret DNA data analysis. He is widely known for helping to develop a breakthrough bioinformatics software program called PICRUSt – pronounced “pie crust” – that predicts which genes are likely to be present in the microbes inside an individual. The program is widely used by researchers world-wide.

In the lab, Morgan and his colleagues pursue an array of microbiomic interests from the effect of exercise and drug absorption on the gut’s microbiome to looking at microbial communities in the soil and their effect on blueberry growth. His team even has a collaborative project examining ocean microbial communities and their role in converting nitrogen in the atmosphere into ammonia and other molecules used by living organisms.

Until sophisticated DNA sequencing came along, Langille says, microbial research was largely confined to microbes that could be grown in the lab. This was a problem because half or more of all microbes still can’t be cultured, and in the microbiome, they function not in isolation but as part of a diverse and intricate ecosystem.

“We have the ability now,” says Langille, “to take DNA sequencers that can generate millions of sequencing reads and use that to profile these large communities.” Scientists can “skip the culturing stuff completely and go right to the DNA. It means we can study the community of organisms as they are, without trying to piece it together one by one.” These revolutionary advances have paved the way for a tidal wave of new research.

The scientific questions are many. How do microbes in the microbiome interact with each other and their host? What do microbes actually do? And what does a healthy microbiomic community look like?

‘Some of these kids respond to the treatment right away’ – Dr. Morgan Langille

“What makes it really hard is that everyone has a different microbiome and it changes pretty readily, depending on what you’re doing, what you’re eating, maybe what drugs you’re taking and any other environmental exposures,” says Langille. Yet, he notes, the changeability factor is also what intrigues researchers who envision harnessing that capacity for new disease treatments and better health strategies.

Gut microbial communities in people with obesity, irritable bowel disease, Crohn’s disease and colitis, for instance, have been shown to differ markedly from those of healthy individuals. The observation has researchers pondering whether the gut’s microbiome can be altered to improve these conditions.

In the area of Crohn’s disease, Langille has been helping Dalhousie pediatric gastroenterologist, Dr. Johan Van Limbergen at the IWK Health Centre, learn how the disease in children is affected by their gut bacteria. They found a specially formulated liquid diet, ingested through a stomach tube, can resolve symptoms for 90 per cent of Dr. Van Limbergen’s patients within 12 weeks, although remissions don’t always last.

“What’s interesting is that it’s just as effective as the common steroid-based treatment but without any of the side effects,” says Langille. “And so from Johan’s point of view, it looks like the diet is actually altering the microbiome. And he really wants to know how that works and if he can use the microbiome profiles to help figure out the treatment – to personalize the treatment more.

‘Some of these kids respond to the treatment right away, and you can take them off the liquid diet and they go on into sustained remission, versus others that chronically go right back to where they were before. From that standpoint you can use the microbiome as a personalized approach, just like you would if you sequenced someone’s genome to hopefully personalize treatments that way.”

Another area of interest is Clostridium difficile, a stubborn and sometimes fatal infection. Langille says that fecal transplants look to be a promising remedy, working by re-ordering the microbiome in an infected gastrointestinal tract with microbes from a healthy human gut. Clinical trials so far have shown the procedure more effective than conventional antibiotic treatments.

In the human health sector, he concedes, “There’s nothing out there as major deliverables yet, but I think in another two to five years you will start to see things come on the market – actual new treatments or diagnostics based on the microbiome.”


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