Alterations in intestinal SKI II bacteria can also be a contributing factor to the pathophysiology of obesity. The intestinal microbiota in both humans and mice consist mainly of Bacteroidetes and Firmicutes phyla. The relative Zebularine proportion of Bacteroidetes is decreased in obese people, and increased when these obese people change to a low-calorie diet. Similarly, genetically obese mice have a 50% reduction in the abundance of Bacteroidetes, in the cecal contents. Interestingly, the mRNA and protein expression of Oatp1a1 in livers of obese mice were diminished to,5% and,15%, respectively, of that in WT mice. In addition, hepatic Oatp1a1 is also suppressed by a high-fat diet in rats. In contrast to mice, the present study shows that Oatp1a1-null mice have a 200% increase of Bacteroidetes, and a 30% reduction of Firmicutes in the large intestine. Thus, there is evidence to suggest that Oatp1a1 expression is altered in the face of metabolic disease such as obesity, and that the function of this transporter is critical for the homeostasis of intestinal bacteria populations. FXR has been shown to play an important role in preventing bacterial overgrowth and maintaining the integrity of the intestinal epithelium. For example, administration of GW4064, a FXR agonist, blocks bacterial overgrowth and translocation in ilea and ceca of BDL mice. In ileum, the majority of intestinal BAs are absorbed in their conjugated forms via BA transporters, namely the apical sodium dependent bile acid transporter and the organic solute transporter a/b. Lack of Oatp1a1 decreases the concentrations of conjugated BAs in ilea, and thus may decrease the influx of BAs into ileal enterocytes, resulting in decreased FXR activation. Although lack of Oatp1a1 had little effect on ileal FXR mRNA expression, it significantly decreased the mRNA expression of ileal SHP, a target gene of FXR. In addition, both ileal Fgf15 and hepatic Fgfr4 mRNA expression tend to decrease in Oatp1a1-null mice. This indicates that Oatp1a1-null mice may have a decreased BA-mediated FXR activation in the ilea, which may contribute to the overgrowth of intestinal bacteria. However, it remains unclear how lack of Oatp1a1 alters the intestinal bacteria. It is also possible that lack of Oatp1a1 alters the disposition of some endogenous substrates, other than BAs, which are important in maintaining normal intestinal functions. In summary, the present study provides a new perspective on the in vivo functions of OATPs/Oatps, which are extensively engaged in drug absorption, distribution, and elimination. The alteration of OATP expression and activities can affect the plasma concentration of drugs, thereby significantly influencing drug toxicities, therapeutic efficacies, and drug-drug interactions. The present study suggests that inhibition of Oatp1a1 in mice may result in an overgrowth of intestinal bacteria and thereby an increase of secondary BAs in serum and intestinal contents. The present study also suggests a potential role of OATPs/Oatps in nutrition and obesity. For example, loss of Oatp1a1 function alters urinary excretion of daidzein and its bacteria-mediated metabolite O-desmethylangolensin, which have been shown to have beneficial effects on obesity, hypertension, cholesterol, and glucose levels in animals and humans. Therefore, the effects of OATPs/Oatps on intestinal bacteria, BA metabolism, and host metabolomics should be considered when studying drug-induced liver injuries and drug-drug interactions. Trypanosomes are protozoan parasites with sanitary relevance, since many members of this group of parasites are causative agents of important and neglected human diseases.