BOSTON (GenomeWeb News) – The Human Microbiome Project — dubbed the “Second Human Genome Project” by some — took center stage at the American Society for Microbiology meeting this week, where scientists bandied about ideas for carrying out such studies most effectively.
At her talk on the “Metagenomics of Human Microbiota” yesterday, Claire Fraser-Liggett, director of the University of Maryland’s Institute for Genome Sciences, expressed enthusiasm about the meeting’s emphasis on metagenomics — particularly in the human environment.
The human microbiome, the collection of microbes in and on the human body, is increasingly of interest for understanding human health and disease, and changes in microbial communities in the body have been linked to everything from immune system function to obesity to cancer.
Such links aren’t entirely unexpected given the oft-quoted estimate that the human body contains ten times as many bacterial cells as human cells (that translates into roughly one thousand bacterial genes for every human gene).
Still, Stanford University microbiologist David Relman said at an ASM press conference earlier this week, even though researchers have been aware of the microbes associated with the human body for hundreds of years, the viral, bacterial, fungal, and single-celled eukaryote communities associated with humans remain poorly understood.
That may change as an explosion of research programs — such as those done under the auspices of the National Institutes of Health’s Human Microbiome Project and others — begin characterizing the non-human parts of the human body.
“This is a relatively new frontier that we’re looking at,” Margaret McFall-Ngai, a University of Wisconsin at Madison medical microbiologist, told reporters.
“It’s clearly the beginning of a new, large international effort,” Fraser-Liggett added, noting that some have already started likening human microbiome research efforts to the Human Genome Project.
But, Fraser-Liggett cautioned, unlike that effort, “it’s going to be more difficult to find a defined endpoint for the microbiome project.” Others expressed similar sentiments. “It seems we have opened up a very large can of worms here,” McFall-Ngai said.
Part of the daunting nature of the human microbiome is the astonishing diversity and variability in microbial communities found both within and between individuals and over time.
Still, new technologies, such as advanced sequencing techniques, are allowing researchers to shed at least some light on the structure and function of the microbes with which we share space and resources. “We are experiencing nothing less than a technology-enabled revolution,” McFall-Ngai said. Such technology comes into play as studies shift from traditional culture-based approaches to much more comprehensive metagenomics methods.
Even so, many say that the potential of such studies makes it all the more important that experiments are carefully designed and adequate for answering as many questions as possible. Researchers agree that there is a need to understand how microbial communities influence the healthy human body before drawing conclusions about their role in disease states. But there are still questions about the best methods and strategies for doing this.
That means, as Fraser-Liggett pointed out, preliminary work needs to consider optimum sampling strategies — including the type and number of samples taken and the methods used — and a host of other experimental design issues.
For example, Fraser-Liggett noted that 16S rDNA-based analyses are useful but far from sufficient for gaining a complete view of microbiomes. Instead she speculated that, since different bugs have overlapping functions, microbiome consensus might actually be at a functional level, with different microbiomes sharing a core set of functions rather than a core group of specific community members.
“I think it’s critically important that functional analysis go hand-in-hand with sequencing projects,” Fraser-Liggett said. “Sequencing alone is not going to provide you with the information you need.”
Still, sequencing will inevitably be a big part of the research. Projects in the US are expected to yield a thousand or more new microbial reference sequences — and with that new data come bioinformatics challenges. “[The bottlenecks] will always, to some extent, be bioinformatics,” Fraser-Liggett said. Still, she added, “I don’t think this is by any means an insurmountable problem.”
The benefits of understanding the human microbiome are predicted to be many. For example, New York University microbiologist Martin Blaser speculated at the press conference that the work may lead to the development of pro- and pre-biotic approaches for maintaining human health. He and others also noted that it may make people more aware of beneficial microbes and how antibiotics alter normal flora. Some, like Relman, predicted that each person’s microbiome could eventually become a medical biometric.
In addition, McFall-Ngai argued that the advances made in understanding microbes associated with the human body will have “ripple effects” that influence other areas of biology as well — from conservation biology to animal husbandry.
Even so, Fraser-Liggett noted, the initial human microbiome research efforts will take time. For example, she cautioned, it’s likely that initial efforts to link microbial communities to health or disease will reveal correlation without providing answers about whether specific microbial communities cause certain human conditions.
“That’s not a failure,” she said. “That’s one step on the road to ultimate success.”