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Microbes do vital work in human gut

Metagenomic analysis shows bacteria, Archaea perform several crucial functions in human metabolism

By | June 2, 2006

Bacteria and Archaea service their human hosts by handling a variety of gut functions, such as metabolizing sugars and amino acids and synthesizing essential vitamins, according to a metagenomic analysis published in this week's Science. "This is a really important paper that applies new technologies to delve into the fact that we're not alone, we're symbionts," Edward DeLong of the Massachusetts Institute of Technology, who was not involved in the paper, told The Scientist. "This is just a first step, but eventually we'll get a better appreciation of how our microbe population varies in health and disease." Microbial genes in the distal gut outnumber human genes by approximately 100 to 1. To investigate the role microbes play in human metabolism, the researchers used genomic techniques to study microbes in their natural environments, particularly the majority of microbes that cannot be cultured. They analyzed DNA sequences in the feces of a healthy man and woman, inferring microbial metabolic functions by comparing the sequences to annotated sequences from microbes with known metabolic pathways. This approach can reveal much about the frequency and function of known genes present in the study sample, but little about genes that are not similar enough to be characterized functionally. As a result, "it's not a sure thing that annotation in databases is correct and function assigned accurately," Jo Handelsman, of the University of Wisconsin at Madison, who has performed metagenomic studies of microbial ecology in soil, told The Scientist. "But the strength of this paper is that it is based on highly conserved functions, so their assignments are probably correct." The researchers were also able to assign significant matches to more genes than previous studies, Handelsman added. The researchers found that microbes perform a variety of crucial gut functions, including handling metabolism of plant polysaccharides, amino acids, and potentially dangerous foreign chemicals, while converting hydrogen to methane and synthesizing essential vitamins. "The message is that our microbial population co-evolved with us to perform functions essential to our health, nutrition, and survival," first author Steven Gill told The Scientist. (Gill completed the study while at The Institute for Genomic Research, but is currently based at the State University of New York at Buffalo, NY.) Microbes in feces don't represent all microbes in the intestinal tract, but genuine intestinal samples would require surgery, noted Julian Davies of the University of British Columbia in Vancouver, not a co-author. "There is no question about the value of this study, but it's early days yet," he told The Scientist. Microbe populations in the two study subjects were similar but not identical, confirming previous studies suggesting that each person may possess unique microbial communities that vary in health and disease. This observation opens up new avenues in personalized healthcare -- for instance, tailoring medicine to microbe genes as well as human genes, Jeremy Nicholson of Imperial College London told The Scientist in an Email. He investigates metabolic phenotyping for individualized drug treatment and was not associated with the study. "Or maybe we can manipulate the microbial communities in some way to improve the effectiveness of drug therapies," he suggested. "It certainly means that human genomes alone are not enough to describe all the important biological variation found in humans." Tabitha M. Powledge tpowledge@the-scientist.com Clarification (posted June 5): When originally posted, the story implied that the researchers used only 16S ribosomal DNA sequences to infer metabolic activity. In fact, they used bulk DNA to infer metabolic activity. Links within this article SR Gill, et al, "Metagenomic analysis of the human distal gut microbiome," Science, June 2, 2006. www.sciencemag.org DeLong, EF. "Archaeal mysteries of the deep revealed." PNAS, April 25, 2006. PM_ID: 16618931 J. Handelsman, "How to find new antibiotics," The Scientist, October 10, 2005. http://www.the-scientist.com/article/display/15764/ A.Constans, "Mining for microbial communities," The Scientist, April 12, 2004. http://www.the-scientist.com/article/display/14597/ J. Perkel, "Microbiology vigil: Probing what's out there," The Scientist, May 5, 2003. http://www.the-scientist.com/article/display/13755/ Sabree, Z.L. et al. "Identification and characterization of the gene encoding the Acidobacterium capsulatum major sigma factor." Gene, April 5, 2006. PM_ID: 16698197 Warren, R. et al. "Functional characterization of a catabolic plasmid from polychlorinated- biphenyl-degrading Rhodococcus sp. strain RHA1." Journal of Bacteriology, November 2004. PM_ID: 15516593 Eckburg PB et al. "Diversity of the human intestinal microbial flora." Science, June 10, 2005. PM_ID: 16407106 Clayton T.A. et al. "Pharmaco-metabonomic phenotyping and personalized drug treatment." Nature, April 20 2006. PM_ID: 16625200
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Comments

June 2, 2006

I am a veterinary microbiologist and the work reported in this article are and have been important to animal health. Veterinarians have observed the importance of the "normal flora" in protection against enteric bacterial pathogens on a daily basis. Especially when treating animals that are infected with Salmonella spp.\nAnd the importance of microbes in the rumen of ungulates and the cecum of horses and other animals are vital to the supply of nutrients for the growth and health of these animals. We all need to know more about this important ecosystem.

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