bilities, do these genes afford their human host? How do they allow for metabolism of all of the undigested polysaccharides and other substances inaccessible by human enzymes? And how does that impact human health and disease? Turnbaugh summarized results from a series of experiments designed to address these questions, with a focus on obesity.

Impact of Gut Microbiota on Energetics and Obesity

Turnbaugh’s interest in obesity was sparked by work conducted in Jeffrey Gordon’s laboratory at Washington University, where Fredrik Backhed and colleagues compared body fat in germ-free mice (i.e., mice raised in an isolator and without any exposure to microbes) to body fat in conventionally raised mice (i.e., mice that had been raised their entire life exposed to microbes) (Backhed et al., 2004). Researchers reported lower total body fat in the germ-free mice but were able to recover the body fat by colonizing germ-free mice with microbial communities harvested from conventionally raised mice. In Turnbaugh’s opinion, the most interesting finding of the study was that conventionally raised mice had more body fat even though they were consuming fewer calories. This was true for both female and male mice and across multiple genetic backgrounds.

Turnbaugh was curious about this “perplexing” phenomenon. How does the microbiome affect the ability of its host to harvest energy from the diet? He and colleagues conducted some studies using 16S ribosomal RNA (rRNA) sequencing to identify phylum-level bacteria in the microbiomes in two different mouse models, ob/ob mice (i.e., mice that chronically overeat because they are genetically deficient in leptin) and diet-induced obese mice (i.e., genetically identical mice that are fed a diet high in fat and simple sugars) (Ley et al., 2005; Turnbaugh et al., 2006, 2008). With both models, the researchers found that lean mice had a moderately greater proportion of Firmicutes (60 percent) than Bacteroidetes (40 percent) but that obese mice had an even greater proportion of Firmicutes than Bacteroidetes. Thus, obesity correlates with increased Firmicutes and decreased Bacteroidetes.

What is the nature of the association? Are the altered microbial communities affecting their hosts in different ways? To answer this question, Turnbaugh and colleagues conducted a microbiota transplantation experiment, where they started with a panel of germ-free recipient mice, all of the same weight and age and with similar other features, and colonized the mice with microbiota samples taken from either an obese or a lean mouse donor (i.e., both ob/ob and diet-induced obese donors). Then they observed the impact of the transplantation over time (Turnbaugh et al., 2006, 2008). Researchers observed about twice as much gain in body fat in mice receiving microbiota transplanted from either ob/ob or diet-induced obese donors, compared to mice receiving microbiota from lean donors (see



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