Genetics in your practice; The microbiome

You are never alone as you travel through life; in fact, each of us is outnumbered on a cellular level by the microflora that travel with us. Estimates place the total number of cells that we carry at a 101 ratio to the number of human cells.

The Human Microbiome Project has been launched in an effort to better understand these fellow travelers by sequencing the entire genome of all these bacteria. The net contribution of this research effort to our understanding of human health and disease will rival that of the Human Genome Project. In the future, the eventual integration of the microbiome project with the genome project will provide unprecedented opportunities to understand the interplay of “nature and nurture.” The National Institute of Health (NH1) and other organizations around the world are funding microbiome research aimed at better understanding our commensal flora.

The five different “microbial communities” targeted by the current research agenda are the gastrointestinal tract, the female urogenital tract, the oral cavity, the nasopharyngeal tract, and the skin.

As the NIH website for the project states, the Human Microbiome Project has set the following goals: determining whether individuals share a core human microbiome, understanding whether changes in the human microbiome can be correlated with changes in human health, developing the new technological and bioinformatic tools needed to support these goals, and addressing the ethical, legal, and social implications raised by human microbiome research.

Currently, we have relatively few practical clinical insights into how and why this exciting area of research matters. But Clostridium difficite colitis and vaginal candidiasis are two examples that provide simple but important lessons about the function of our microbiome as a protective mucosal barrier. As every clinician knows, when antibiotics are used to treat infection, the critical balance within these communities of flora can become altered community are usually relatively short term and treatable.

But a study published last year points to a new paradigm of longer-term and perhaps lifelong consequences of altered microbiomes. The research showed that the pathogenic potential of Helicobacter hepaticus in a mammalian colitis model is altered by the presence of different strains of Bacteroides fragilis. The presence or absence of a particular bacterial polysaccharide expressed on the microbial cell surface of B. fragilis controls whether there is an inflammatory response to H. hepaticus.

Among the implications of this research is the proof of concept that a staged exposure to microbes can lead to an inflammatory on-off switch in the colon. It is conceivable that within the practice life of many of the readers, we could be engineering the gastrointestinal microbiome to induce the regression of colonic polyps or to treat inflammatory bowel disease.

Some other general areas of clinical interest to watch for as microbiome research progresses include:

• Routine manipulation of human mucosal microbiomes to improve barrier defenses.

• Optimization of human immune response through altered microbial communities.

• Use of microbes as on-off switches for human cellular pathways.

• The discovery of new microbes.

Regarding new microbe discovery, the Human Microbiome Project promises a fascinating opportunity to discover and ultimately understand whole classes of human commensal microbes that have not yet yielded any of their secrets simply because they cannot be cultured via any currently available technique.

The study of the microbiome and its interaction with the human genome is sure to reveal much about human health and disease.