Biologists’ knowledge of the human microbiome has exploded in the last decade, driven by advances in big data and DNA testing. The richness of the information collected raises myriad new and exciting questions for scientists.
As with any new realm of knowledge, a first effort consists in categorisation. We know that thousands of species of bacteria inhabit the gut, for example, but we may discover their true diversity to be much greater. As for viruses, the most abundant biological entities on Earth, only 5-25% of them have been classified so far.
This is, in part, because singling out a specific microbe can be challenging: Microbes often need a community of other microbes to grow, making monoculture difficult. Developed under the Human Microbiome Project and commercialised by GE since last year, a new technology now enables researchers to isolate a single cell’s DNA and to reproduce it in just a few hours. The process, which uses Phi29 DNA polymerase, enables researchers to grow micrograms samples from samples as light as one femtogram (a billionth of a microgram). Such technologies could facilitate single-cell sequencing and, over time, enable researchers to understand how a specific microbe contributes to the microbiome.
While that work goes ahead, others are pursuing the exploration of the molecular mechanisms through which bacteria interact with one another. “We know virtually nothing about most microbiota metabolites that are produced in vivo, even though these are the key molecules that microbes use to converse with each other and the host,” notes Brett Finlay of the University of British Columbia in a paper published earlier this year. John Cryan of University College, Cork, agrees. “We really have to get at these mechanisms,” he says.
Medical treatments may not need to wait for that. Plenty of drugs are currently in use whose precise mode of action is not known. But they still need clinical testing. So, emphasises Mr Cryan, do any claims for probiotics—foodstuffs containing bacteria, or bacteria themselves, that are consumed for some supposed benefit.
Microbe engineering is another area attracting interest—and investment. Just last month, the Gates Foundation issued a call for proposals for experiments on manipulating the gut microbiome with bacteriophages in ways that might prevent malnutrition in children in the developing world.
At the opposite extreme from this investigation of the potential of minuscule bacterial viruses is the only manipulation of the microbiome that has proven successful so far: a total faecal microbiome transplant (FMT) to relieve chronic intestinal infection caused by the Clostridium difficile bacteria. Much work remains to be done, however. This includes establishing which bacteria are actually beneficial, standardising the faecal or faecal-derived cultures that are used and setting up the appropriate regulatory system—FMT is still considered an investigational drug in the US.
The new worlds of the microbiome also raise questions that go beyond direct applications. The fact that microbes were here before any other kind of life, for example, begs for reaching an understanding of how humans and their microbial communities co-evolved. That may seem like a distant goal, but it is one systems and computational biologists have started to pursue, one cell at a time. For now, efforts have focused on Mycoplasms genitalium, one of the simplest bacteria we know. Scaling up to trillions of bacteria, to thousands of species and to multitudinous interactions with human cells is still a long way off.
In the end, virtually no aspect of human biology is likely to remain untouched by microbiome research. As Mr Cryan emphasises, “What’s great about this field is that it is extremely multidisciplinary and people are all talking to each other.”
This post first appeared on GE LookAhead. Publication does not imply endorsement of views by the World Economic Forum.
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Author: Jon Turney is a contributor at GE LookAhead.
Image: A researcher, seen through a window, prepares DNA in a laboratory. REUTERS/Robert Pratta.