The present studies examine intestinal, metabolic, and behavioral alterations in germ-free (GF) animals. The first set of experiments examine preference and acceptance for sweet solutions, sucrose and saccharin, in GF C57Bl/6J mice with associated changes in expression of lingual and intestinal nutrient-sensing sweet taste receptors, T1R2 and T1R3, and the glucose transporter, SGLT1. It demonstrates that GF mice consumed more of the highest concentration of sucrose relative to NORM controls, with an increased expression of intestinal T1R3 and SGLT1. The second set of studies examine if findings of increased sucrose intake extend to fat, and whether the GF mice display alterations in lingual and intestinal fat sensors as well as intestinal satiety peptides. We found that GF mice display increased intake and preference of fat at high and low concentrations, respectively. Additionally GF mice display decreased fatty-acid GPRs and satiety peptides in the intestine, decreased circulating gut peptide levels, increased lingual fat detecting receptors, and increased markers of fatty-acid metabolism, all of which are adaptive effects to the chronically depleted energy state of the GF mice. The final succession of experiments was to determine if the GF state, with its associated decreases in adiposity and chronic fasting state in mice, is present in the GF rat model. Interestingly, we found that GF rats display similar or increased levels of body adiposity, with decreased markers of liver lipogenesis, yet increased lipogenesis in adipose tissue associated with adipocyte hypertrophy. Overall, these data demonstrate that absence of gut microbiota in mice leads to increased energy consumption of sugars and fats associated with alterations in oral and intestinal nutrient sensors while the gut microbiota in the F344 does not play a pivotal role in adiposity
