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Genome Giants Catalogue our Mouth Bugs

June 23, 2003
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Nature — At least 500 species of microbe lurk in the average gut, 500 in the mouth and another 500 in the vagina. A new project aims to log every one – and figure out how they contribute to disease.

The swarms of bacteria and viruses that call our body home are vital: those in the gut, for example, are thought to aid food digestion and muscle out more harmful bugs. But because most of the creatures will not grow in the lab, they also remain largely anonymous.

To find the mystery microbes, researchers at the Institute for Genomic Research in Rockville, Maryland, plan to extract the crud from a body cavity and chuck it into DNA sequencing machines – the same ones used to unravel the human genome. Analysing the sequences, they hope, should reveal exactly what grows where.

Open mouthed

Starting with the mouth, project leaders Steve Gill and Karen Nelson have already extracted DNA from a scraping of plaque, the bacterial gunk that builds up on gums and teeth.

More than 40% of these genetic sequences have never been seen before, they say, and are probably new genes from known bacteria or completely new species.

Simply identifying the creatures with which we are so intimate is intriguing for some. “It’s a fundamentally interesting thing to do,” says Julian Parkhill who studies bacterial genetics at the Sanger Institute in Hinxton, UK.

Until now, most sequencing studies have rejected obscure bugs for more famous villains, says Parkhill, such as E. coli or Salmonella typhimurium. The few scientists who have attempted to survey the body’s flora usually determined the sequence of one gene; facilities to power through vast amounts of DNA have only recently been developed.

The obscure organisms the new study will find are probably our greatest allies. When antibiotics wipe out some of the gut’s natural flora, pathogens such as Clostridium difficile can multiply, causing diarrhoea. And research has shown that a single bacterial strain added to mice that lack other gut flora boosts the growth of blood vessels to the intestinal lining.

Ultimately, the new analyses should reveal which combination of bugs contributes to a healthy body and which to diseases. The team is already comparing the microbes on healthy teeth with those in a person suffering severe gum disease.

Chips with everything

Once all the creatures in a body cavity have been logged, they could be put to work on a diagnostic gene chip. A chip holding DNA sequences of bugs in the vagina, for example, could be washed over with a vaginal sample and examined for patterns characteristic of good health or a particular type of sexually transmitted disease.

Bowel-obsessed people might even keep a gut chip in their toilet bowl, concedes David Relman of Stanford University in California, who is involved in the project. The results might also help in the development of pro-biotic foods, he says, which are loaded with healthy bugs and aim to supplement natural flora: “These strategies are very crude right now”.

Nelson’s group is already straining DNA from human faecal samples, with the aim of comparing them with patients with the intestinal disorder Crohn’s disease, colon cancer or simply different diets. Next on the list, after skin and vagina, are ears, nose and stomach, says Nelson: “We’re going to take them one by one”.

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