Sci. Aging Knowl. Environ., 3 November 2004
Vol. 2004, Issue 44, p. nf99
[DOI: 10.1126/sageke.2004.44.nf99]


Gut Instinct

Intestinal microbes promote fat buildup in mice

Mitch Leslie

Unsuccessful dieters complain that their stomachs rule their lives. That might be an exaggeration, but the denizens of the digestive system could dictate how much fat an individual stockpiles, according to new research on mice. Bacteria in the intestine signal rodents to amass fat, the work shows, and the results might help researchers understand why some people gain weight and others don't.

About 500 trillion microbes throng our intestines. Researchers have long known that these companions break down complex sugars we can't digest and manufacture vitamin K, which is essential for blood clotting. Molecular biologist Jeffrey Gordon of Washington University in St. Louis, Missouri, and colleagues wanted to find out whether the bugs exerted pervasive effects on metabolism.

They studied germ-free rodents that dwell in antiseptic cages, breathe filtered air, and consume sterilized rations. The researchers "infected" some of the mice by dabbing them with intestinal contents from normal mice. Although the recipients gained no weight, they turned flabby. After 2 weeks, newly bacteria-ridden males carried 57% more fat than their bug-free brethren. Female fat storage swelled 85%. To probe why adding bacteria also added fat, the researchers fed some mice a solution containing a chemical relative of glucose, then killed the rodents and measured how much of the compound their intestines had absorbed. The bug-carrying animals sopped up twice as much as did germ-free rodents, suggesting that intestinal bacteria boost sugar absorption.

To explore how that sugar infusion might become fat, the team gauged the activity of two genes that encode proteins that hike fatty acid synthesis in the liver. Both genes worked harder in the "infected" mice than in microbe-devoid rodents. The researchers also found that the activity of LPL, a molecule that coaxes fat cells to imbibe fatty acids and store triglycerides, soared 122% after the mice got the bugs, perhaps because the bacteria also diminished the intestine's production of Fiaf, a protein that squelches LPL activity. As a test of that idea, the team measured fat buildup in germ-free mice lacking the gene for Fiaf. They toted the same amount of fat as did infected rodents with Fiaf, and they gained only a smidgen of blubber after being exposed to bacteria. Together, the results suggest that intestinal inhabitants increase sugar absorption, stoking the activity of genes that spur fat buildup and shackling a fat-fighting protein. It's too early to start blaming human obesity on microbes, Gordon cautions. But an overweight person might host a different mixture of bacteria than a thin person, and that combination of bugs might stimulate the body to soak up more nutrients and stow more fat, the researchers speculate.

Researchers have focused on human genes that induce weight gain or on environmental variables such as diet and exercise, says endocrinologist Mitchell Lazar of the University of Pennsylvania in Philadelphia. But this work identifies "an important factor at the intersection between our environment and our genes that's not been considered." Gastroenterologist Gary Wu, also of the University of Pennsylvania, says, "It's a provocative paper. Bacteria in the gut may have a significant role in metabolism." Further work might reveal whether heeding our gut makes us fat.

November 3, 2004
  1. F. Bäckhed et al., The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. U.S.A., 25 October 2004 [e-pub ahead of print] [Abstract] [Full Text]
Citation: M. Leslie, Gut Instinct. Sci. Aging Knowl. Environ. 2004 (44), nf99 (2004).

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