Don't look now, but you are surrounded

It is somewhat unsettling to consider that we are outnumbered by microbes in our own skin by a factor of about ten cells to one. The spectrum of organisms runs from parasitic, saprophytic, and commensal to symbiotic. Our bodies are unique ecosystems that remain largely unexplored to date—this domain has become known as the human microbiome. Given the millions of years of co-evolution of microbes with our species, our ecosystems are quite complex and relate to both health and disease. Most of biomedical microbiology has focused on pathogens, however, overt pathogens represent only a tiny fraction of the microbial species on and in our persons.

Genomic technologies, including next-generation sequencing, have provided new tools to study our personal ecosystems. The Human Microbiome Project has set about systematically mapping the number and types of organisms present at a variety of sites in the human body.

Early in this endeavor, unexpected findings have changed our thinking about our other microbial selves. For example, it turns out that the skin of the forearm has more microbial diversity than many other sites, and that microbial communities can differ from the right to the left hand in the same individual. Additionally, there are extremely high levels of variability of skin organisms between individuals, perhaps as much as an 80% to 90% difference depending on the site sampled.

We are hosts to many organisms that have never been successfully cultured due to exacting environmental needs; the extent to which such organisms have a role in disease pathogenesis remains unknown. Simply defining the spectrum of a “normal” microbiome has turned out to be problematic. Factors like how we brush our teeth, what we eat, and the people we have sex with all influence our microbial “signatures.” These signatures turn out to be unique. For example, as I type this article I am depositing microbial genomic residue on my keyboard that could potentially identify me as a user of this laptop several weeks from now.

Long before Pasteur and Koch, manipulation of the microbiome for ill and salutary effects has been an unconscious activity of day-to-day human life. Though we don't often think of it in this way, cooking foods, showering, and brushing one's teeth are daily attempts to keep unwelcome microbiota at bay.

As clinicians, we engage in crude microbiome engineering more consciously. Examples include the use of sterile technique and prescribing antibiotics. Often, our prescribing seeks to target a single pathogen, for example, prescribing penicillin for a Streptococcus infection in strep throat. In actuality, the “magic bullet” of penicillin amounts to indiscriminate firebombing of all of our microbial communities susceptible to penicillin (hence gastroenterological disturbances and yeast infections).

Luckily our microbial guests are quite resilient and capable of self-correction. In fact, we would rapidly expire without their ability to balance themselves in the context of our host defenses. A better understanding of the human microbiome may result in changes in how antibiotics are developed and prescribed.

Recently, interest has surged in the use and commercialization of the human microbiome through its active manipulation with probiotics. According to the World Health Organization, probiotics are “live microorganisms which when administered in adequate amounts confer a health benefit on the host.” At the more familiar end of the probiotic spectrum are products like active culture yogurts and Lactobacillus supplements. Because these products are very likely benign and possibly beneficial, clinicians have been prescribing them or at least accepting their patients' use of them for decades.

More recently, companies have been touting the use of probiotics in products from toothpaste to cosmetics. The efficacy of such products remains largely undefined. Probiotic products are treated as nutritional substances and are therefore not highly regulated in the U.S. As such, health care consumers should be aware of the potential for variability among manufacturers and batches, as well as the tenuous evidence for benefit of many probiotic products.

A new twist in the probiotic arena will likely cause significant controversy. Genetically modified organisms tailor-made to treat conditions are currently in development. An early example of the potential of this approach comes from research on inflammatory bowel disease. A study by Mohamadzadeh and colleagues published in the Jan. 31, 2011 Proceedings of the National Academy of Science reported substantial benefit in a mouse model of Crohn's disease exposed to genetically modified L. acidophilus organisms. Though considerable work is yet to be done, human clinical trials for such products would seem to be on the near horizon. It is conceivable that organisms intended for use on or in the human body could be modified to produce or degrade a wide variety of compounds relevant to diverse conditions. The marketing of living genetically modified organisms intended for use on or in the human body as a therapy would likely prompt reconsideration of the probiotic regulatory status quo.

Issues related to the marketing and use of probiotics in both the health and cosmetic industries were a source of considerable discussion at the most recent Ethical, Legal and Social Implications Congress held last month at the University of North Carolina in Durham. Genetically modified probiotics will likely be the subject of considerable scrutiny over time, much as genetically modified foods have been. Clinicians and policymakers are very likely to be subject to questions specifically related to such products, and keeping abreast of the science will be no small task.