ROCKVILLE, Md.—In a recent issue of Science, researchers from The Institute for Genomic Research (TIGR) and colleagues examined the biological universe of the human colon and found more than 1,000 microbial species. While many of these are passive or pathogenic visitors in the human body, several are absolutely required for human health, explains Dr. Steven Gill, lead author of the study and now a professor at the State University of New York-Buffalo.
"A shift within this population, often leading to the absence or presence of beneficial microbes, can trigger defects in metabolism and development of diseases such as inflammatory bowel disease," he says.
As an example, Gill offers a study led by Dr. Jeffrey Gordon at the University of Washington School of Medicine in St. Louis that looked at the effect of microbial flora on fat storage. As the scientists published in the November 2004 issue of Proceedings of the National Academy of Sciences, changes in microbial ecology resulting from Western diets may function as an environmental factor that affects predisposition toward storage of energy and obesity.
Gill and his colleagues probed the ribosomal DNA of microbes from colon samples of two healthy people who had been antibiotic-free for a year. In total, they analyzed about 78 million base pairs in more than 2,000 PCR reactions. The metagenomic analysis resulted in the identification of more than 60,000 genes, more than double the size of the human genome.
The researchers then compared the gene sequences to those found in a variety of metabolic pathway databases, correlating the possible metabolomes of the gut microbes with known pathways. The work provided insights into key metabolic pathways influenced by specific microbial strains.
For example, the researchers found evidence of a vitamin synthesis pathway that was originally only thought to occur in pathogenic bacteria and therefore had represented a possible target for new antibiotics. The current study, however, suggests that antibiotics directed against the enzymes involved in this pathway may prove detrimental to the natural microbes and therefore to humans. In essence, they've averted a potential adverse drug event before the drug was even developed.
The next step will be to begin examining the differences between the microbiomes of healthy and diseased subjects, explains TIGR's Dr. Kelly Nelson, such as those with Crohn's disease or cancer.
The researchers still have much sequencing work ahead before they can say they have painted a definitive picture of the microbiome or microbial community of the human gut. At the same time, however, preliminary results suggest that drug developers will need to take a "superorganismal" view of human health.
"Humans exist with a large and diverse community of bacteria thriving in and on their body," Gill says. "The genetic landscape is superorganismal only in the sense that we are now considering both the human genome and the combined genomes of the microbiome or microbial community."
