For years, medical microbiology was in a rut with most research focused on the few bacteria that grow in captivity and ignoring the rest. About a decade ago, Jeffrey Gordon MD and his colleagues around the world began switching to metagenomics -newly developed culture-independent rapid sequencing technologies- and were confronted with an astounding variety of previously unknown microorganisms. These included many of the 100 trillion microbes living on humans, the majority them in the gut where they are thought to exert a profound influence on many aspects of our physiology and nutrition.
Germ-free Mice Eat More and Stay Thinner than Regular Mice
Conventional research hinted that obesity had a microbial component; for example, researchers in Gordon’s lab at Washington University School of Medicine in St. Louis, Missouri, knew that “germ-free” mice were leaner than their microbe-laden, conventionally-raised counterparts, even though the germ-free animals were consuming about 30% more calories each day. Moreover, when gut microbes from the conventionally-raised mice were transplanted into germ-free animals there was an abrupt increase in recipient’s body fat.
Twin Studies Link Obesity and Gut Microbes in Humans
By 2004 the scientists in Gordon’s team had their advanced sequencing technologies up and running and began using metagenomics to identify and compare the microbial genes in mice as well as in the intestines of obese and lean adult identical and fraternal twins. The twin studies showed, not surprisingly, that families share more similar gut microbial communities than strangers and that these microbes are acquired early in life.
Then came the eureka moment: there seemed to be a link between obesity and the microbes living in subjects’ intestines. (Two groups of bacteria dominate the gut, the Bacteridetes and Firmicutes and in these investigations their relative proportions were altered in favor of the Firmicutes in obese compared to lean individuals.)
Human Gut Microbes Successfully Transplanted to Germ-Free Mice
Encouraged, the researchers transplanted gut microbes from healthy humans to germ-free mice. “Amazingly,” says Gordon, “most of the human bacteria successfully established themselves in the mice, enabling more precisely-controlled ‘clinical’ studies than would be possible on people.”
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