, 1970, 1983; Booijink et al., 2010), our data indicate that the microbiota of the small intestine consists screening libraries of facultative and strict anaerobes. However, we observed a large proportion of anaerobes from the Clostridium cluster XIVa in our effluent samples, such as Coprococcus eutactus and relatives, which was detected up to 6% of the total community. Therefore, our data do not confirm a recent study that concluded oxygen exposure to have a major impact at the end of the terminal ileum in ileostomy patients (Hartman et al., 2009). Although we cannot fully exclude a potential role of oxygen, we consider it more likely that the absence of a colonic reflux explains our observations. We generically profiled the microbiota of non-medicated subjects that had an ileostoma for many years, whereas Hartman et al.

(2009) studied selected microbial targets by quantitative PCR in patients that recently underwent surgery, which might explain the difference. In this study, we generated a combination of molecular ecological data sets to describe the small intestine, using an ecosystems biology approach (Raes and Bork, 2008). On the basis of all data, we hypothesize that microbial communities in the human small intestine are dependent on the capacities of microbes to rapidly import and ferment the available carbohydrates, which are combined into a metabolic cooperative network to support maintenance of various microbial groups (Figure 4). This model is in agreement with the dominance and high-level activity of the small intestinal streptococci, which are r
Functioning as a xenosensor, human constitutive androstane receptor (hCAR, hCAR1, or NR1I3) regulates numerous hepatic genes that encode phase I oxidation enzymes [e.

g., cytochrome P450 (CYP)], phase II conjugation enzymes (e.g., UDP glucuronosyltransferases), and phase III drug transporters (e.g., multidrug resistance MDR1) upon xenobiotic stimulation (Sueyoshi et al., 1999; Honkakoski et al., 2003; Qatanani and Moore, 2005; Stanley et al., 2006). Through induction of these enzymes and transporters, hCAR is also involved in the metabolism and secretion of endogenous signaling molecules such as cholesterol and bilirubin, where bioaccumulation of these endobiotics is associated with disease conditions such as cholestasis and hyperbilirubinemia (Sugatani et al., 2001; Tien and Negishi, 2006).

In addition, recent studies also extend the roles of CAR to the regulation of various physiological and pathological processes such as energy homeostasis, cell proliferation/apoptosis, and tumor promotion (Kodama et al., 2004; Maglich et al., 2004; Yamamoto et al., 2004; Huang et AV-951 al., 2005). Thus, the need for understanding the molecular mechanisms governing CAR activation, and developing novel tools for in vitro identification of hCAR activators has become evident.