First analysis of the genes of a community of human microbes

Researchers have completed the first analysis of the genes of a community of human microbes, an accomplishment that has far-reaching implications for clinical diagnosis and treatment of many human diseases.

Results of the analysis, conducted by a team headed by UB microbiologist Steven R. Gill, Ph.D., appear in the journal Science.

Gill, who conducted the research while at The Institute for Genomic Research (TIGR) with colleagues from TIGR, Stanford University and Washington University, analyzed the DNA of microbes in the human distal gut as a "community-of-the whole" -- the next frontier in the field of genetic research called metagenomics.

"The human genome is an amalgam of human genes and the genes of our microbial 'selves,'" said Gill. "Without understanding the interactions between our human and microbial genomes, it is impossible to obtain a complete picture of our biology.

The human genome lacks some essential enzymes that break down the food we eat into energy essential for survival, a situation which prompts Gill to note out that while bacteria could survive perfectly well without their human hosts, humans would be doomed without their bacterial partners.

"The ultimate goal of the work," he said, "is to develop tools for clinicians to use in treating disease. With this kind of knowledge, we can use biomarkers to identify the bacterial population of the individual. Clinicians then can adjust the population of bacteria to make that person well. Such an analysis also would determine which bacteria are resistant to which antibiotics, and help determine the proper drug to administer.

In the future, healthy individuals could undergo a metagenomic analysis of their gut to determine their immune status and susceptibility to certain diseases, Gill said.

Jeffrey I. Gordon, M.D., a major contributor to the research from the Center for Genome Sciences at Washington University, noted that this gut "microbiome" project is an important starting point for developing new drugs for 21st-century medicine.

"Our microbial partners have undoubtedly developed the capacity to synthesize novel chemical compounds that help establish and sustain their mutually beneficial relationships with us," said Gordon.

"Prospecting for these 'natural products' and characterizing the pathways through which they operate should provide new insights into the function of many of our human genes, new ways for defining our health, new ways for identifying impending or fully manifest diseases, plus new treatment strategies."

Although scientists have published metagenomic analyses of samples from other environments, including soil and the Sargasso Sea, this is the first publication of an analysis of human-residing organisms. The researchers chose to investigate the colonic microbiome because fecal samples are readily accessible, because the human gastrointestinal tract is the most densely populated microbial community in the body, and because these microbes perform many critical functions.

Samples for the analysis were derived from two unidentified individuals. The researchers know only that one is male and one is female; one is a vegetarian, one is not. Both contributors had received no antibiotics during the past year, insuring that their population of intestinal flora was "normal" and stable.

Metagenomic analysis of the two microbial communities for their potential to carry out necessary functions of human metabolism showed that both had ample concentrations of essential bacteria, but comparison of the two identified significant differences.

One subject was "enriched" -- host to more bacteria of a given category than expected -- for energy production and conversion, carbohydrate transport and metabolism, amino acid transport and metabolism and several other functions.

"This metagenomics analysis begins to define the gene content and encoded functional attributes of the gut microbiome in healthy humans," stated Gill. "In the future we hope to assess the effects of age, diet and diseases such as IBS, cancer and obesity in the microbial community of the distal gut in people living in different environments."

Sampling the gut microbiome periodically, as well as those of other sites, such as the mouth and skin, may allow scientists to determine the effects of environmental change on our "microevolution," said Gill.

Additional authors on the paper are Robert T. DeBoy, Claire M. Fraser-Liggett and Karen E. Nelson from TIGR; Mihai Pop from University of Maryland; Paul B. Eckburg and David A. Relman from Stanford University; and Peter Turnbaugh and Buck S. Samuel from Washington University.