ANDRZEJ KRAUZEA decade ago, gut microbiologist and genomicist Jeffrey Gordon’s postdoc Fredrik Bäckhed at Washington University in St. Louis made a startling discovery: adding gut microbes from normal, healthy mice to germ-free mice significantly increased the latter’s body fat (PNAS, 101:15718-23, 2004). This finding prompted another of Gordon’s postdocs, Ruth Ley, to suggest that University of Colorado computational biologist Rob Knight apply his new microbe-comparing computational tools to obese and lean mice. “I thought it seemed like a long shot” that they would see significant effects, recalls Knight, now at the University of California, San Diego, in an email. The long shot paid off, however, with a 2005 paper in PNAS that found that obese and lean mice indeed had different gut microbiomes (102:11070-75). The insight ultimately launched deeper investigations into the relationship between the microbiome and obesity.
The differences in bacterial diversity that Knight and his colleagues identified between lean and obese mice—notably in the proportions of Firmicutes and Bacterioidetes species—were later confirmed in humans, and follow-up studies found that implanting the microbes from either an obese mouse or an obese human into germ-free mice increased lean animals’ body weights on a high-fat diet, compared to controls that got microbes from lean individuals of either species. Further research has demonstrated that a high-fat diet itself can change the relative abundance of microbial species in the gut and lower the overall diversity. Nevertheless, how and why these microbial and body weight changes occur, and how we might manipulate our microbes to combat obesity, are still topics of debate.
We are at the beginning ...
