Saturday, April 24, 2010

Genetics in the Gut

Outnumbering our human cells by about 10 to one, the many minuscule microbes that live in and on our bodies are a big part of crucial everyday functions. The lion’s share live in the intestinal tract, where they help to fend off bad bacteria and aid in digestion. But as scientists determine what microbes are actually present and what they are doing, they are discovering that the bugs play an even larger role in human health than previously suspected—and perhaps at times exerting more influence than genes themselves.

A team that included Junjie Qin and Jun Wang of BGI-Shenzhen (formerly the Beijing Genomics Institute) completed a catalogue of some 3.3 million human gut microbe genes. The work, published in the March 4 Nature, adds to the expanding—but nowhere near complete—census of intestinal species. (Scientific American is part of Nature Publishing Group.)

The 3.3 million genes were a good deal “more than what we originally expected,” Wang says. The number was especially surprising given that the microbiota tended to be very similar across the 124 individuals the scientists sampled in Denmark and Spain. The team sequenced 576 billion base pairs, much larger than past work that found three billion base pairs. “These bacteria have functions that are essential to our health: they synthesize vitamins, break down certain compounds—which cannot be assimilated by our body—[and] play an important role in our immune system,” Wang points out.

Another group, led by Andrew Gewirtz of Emory University, turned its attention to a particular host gene that seems to affect these intestinal inhabitants. It found that in mice, a loss of one key gene led to a shift in microbiota communities and a rise in insulin resistance, obesity and other symptoms of so-called metabolic syndrome (a cluster of these conditions).

Gewirtz and his co-workers studied mice bred with the genetic deficiency: an absence of Toll-like receptor 5, or TLR5, which has a hand in immune response. They wanted to see how it might change microbial gut communities and metabolic health—and try to understand the order in which the changes were happening. “Obesity is associated with insulin resistance and type 2 diabetes,” Gewirtz says. But “which comes first is not entirely clear.”

As the researchers described in their paper published online March 4 by Science, they found that mice without the TLR5 gene—even when put on restricted diets—still showed insulin resistance, suggesting that the condition might lead to obesity rather than the other way around. But if these mice were allowed to eat as they pleased, they consumed 10 percent more than their peers and, by 20 weeks old, had body mass indexes that were 20 percent higher...

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