Q&A: Medicinal microbiota

The human microbiota -- the communities of commensal bacteria that live in our gut, mouth, and on our skin -- have recently been hailed as a linkurl:forgotten organ,;http://www.nature.com/embor/journal/v7/n7/full/7400731.html and praised for the positive impact they have on our health. Recent research has suggested that the 10¹⁴ or so organisms, representing more than linkurl:500 species,;http://www.ncbi.nlm.nih.gov/pubmed/15894105 influence ailments such as inflammatory bowel disease, obesity, asthma and type I diabetes. The Scientist spoke with linkurl:Justin Sonnenburg;http://med.stanford.edu/profiles/microimmuno/researcher/Justin_Sonnenburg/ and linkurl:Michael Fischbach,;http://www.fischbachgroup.org/ microbiologists from Stanford University and the University of California San Francisco respectively, about potential therapeutics that target the human microbiota, the subject of a perspective linkurl:piece;http://stm.sciencemag.org/content/3/78/78ps12.abstract they authored, published today (April 13) in Science Translational Medicine.The Scientist: What is the fundamental idea behind using microbiota in medicine?

Michael Fischbach (left) and Justin Sonnenburg
Images: Courtesy of respective subjects

Justin Sonnenburg: The microbiota appear to relate to everything. This isn't at all startling as soon as you start to realize that the microbiota is wired into facets of immune regulation, metabolism, aspects of the nervous system. You would basically not expect a facet of human biology not to be influenced in some either direct or indirect way by what the microbiota is doing.Michael Fischbach: If we allow ourselves to think a little bit freely, one might imagine the differences in the composition of these microbiota that you see between healthy people and, say, people with Crohn's disease or one of the other inflammatory bowel diseases. Whether or not that difference is a cause or a consequence of the disease, you can imagine that fixing it would help treat at least the symptoms of the condition.TS: How might the microbiota be manipulated for human health benefits?JS: The concept of gene therapy has been around for quite a while and it is fairly evident that we should think about these microbes and their collected genome as an extended portion of our own genome. Since there's some plasticity in this community, in terms of being able to change and modulate what the genes are doing and what genes are present by changing community membership, we can actually leverage this plasticity in ways that we can't for the human genome. MF: I think that, for a long time, pharmaceutical companies or biotechnology companies who have been thinking about developing drugs that relate to bacteria have always been thinking about killing them. What I suspect will happen in the coming years is that people will begin realizing that they can design a drug that's targeted to bacteria living on or inside of us that is not meant to kill them. In some cases it could be meant to help them grow, in other cases it could be meant to change their function, maybe to induce them to produce a molecule that they otherwise would not have produced, or perhaps to get them to help break down fat or cholesterol or something else that we don't want to have around in our gut. There are lots of thing you can imagine trying to do with a drug that wouldn't be killing these bacteria.I think it's the realization that, in the same way that we think of drug targets that are encoded by the human genome, we should think about the microbiome as encoding a huge number of drug targets and ask the question, What would happen if we modulate these drug targets? TS: These surely are communities of bacterial and, as such, could effecting even one change alter their entire structures?

Bacteroides fragilis, an obligate gut microbe
Image: CDC

JS: That gets to one the concept of microbial ecology and whether we can take a systems view of the microbiota and learn how, for instance, addition of a single polysaccharide or a single organism may cause ripples that affect other community members indirectly through metabolic links and other sorts of interactions.MF: It is the case that there are very few perturbations you can make that won't, as Justin said, ripple through the community. Mapping changes in community composition to what's really important, the changes in function, is going to be the next big question.J.L. Sonnenburg and M.A. Fischbach, "Community Health Care: Therapeutic Opportunities in the Human Microbiome," Science Translational Medicine, 3(78), doi: 10.1126/scitranslmed.3001626, 2011.
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[3rd November 2010]