How much does the microbiota influence the host's phenotype? Ridaura et al. ([1241214][1] ; see the Perspective by [ Walker and Parkhill ][2]) obtained uncultured fecal microbiota from twin pairs discordant for body mass and transplanted them into adult germ-free mice. It was discovered that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Moreover, obese-phenotype mice were invaded by members of the Bacteroidales from the lean mice, but, happily, the lean animals resisted invasion by the obese microbiota.

 [1]: http://www.sciencemag.org/content/341/6150/1241214.full
 [2]: /lookup/doi/10.1126/science.1243787

/pdf/gut-microbiota-from-twins-discordant-for-obesity-modulate-5aeltwsuvw.pdf

Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

https://cyberleninka.org/article/n/567486.pdf

A review on polycyclic aromatic hydrocarbons: Source, environmental impact, effect on human health and remediation

We provide here a list of 221 P450 genes and 12 putative pseudogenes that have been characterized as of December 14, 1992. These genes have been described in 31 eukaryotes (including 11 mammalian and 3 plant species) and 11 prokaryotes. Of 36 gene families so far described, 12 families exist in all mammals examined to date. These 12 families comprise 22 mammalian subfamilies, of which 17 and 15 have been mapped in the human and mouse genome, respectively. To date, each subfamily appears to represent a cluster of tightly linked genes. This revision supersedes the previous updates [Nebert et al., DNA 6, 1–11, 1987; Nebert et al., DNA 8, 1–13, 1989; Nebert et al., DNA Cell Biol. 10, 1–14 (1991)] in which a nomenclature system, based on divergent evolution of the superfamily, has been described. For the gene and cDNA, we recommend that the italicized root symbol "CYP" for human ("Cyp" for mouse), representing "cytochrome P450," be followed by an Arabic number denoting the family, a letter designating...

https://www.liebertpub.com/doi/pdf/10.1089/dna.1993.12.1

The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature.

Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.

The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an increased risk of cardiovascular disease and diabetes. The metabolic syndrome can be d...

Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation

Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity.

https://www.jstage.jst.go.jp/article/jjp/86/3/86_3_302/_pdf

Mechanism of 7,12-dimethylbenz[a]anthracene-induced immunotoxicity: role of metabolic activation at the target organ.

Aims

To compare the effects of grapefruit juice (GFJ) on the pharmacokinetics of pitavastatin and atorvastatin.



Methods

In a randomized, four-phase crossover study, eight healthy subjects consumed either GFJ or water t.i.d. for 4 days in each trial. On each final day, a single dose of 4 mg pitavastatin or 20 mg atorvastatin was administered.



Results

GFJ increased the mean AUC0−24 of atorvastatin acid by 83% (95% CI 23–144%) and that of pitavastatin acid by 13% (−3 to 29%).



Conclusions

Pitavastatin, unlike atorvastatin, appears to be scarcely affected by the CYP3A4-mediated metabolism.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.2005.02462.x

Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin.

Based on information of the nucleotide sequence obtained from rat genome clones, a new CYP3A (CYP3A62) cDNA was isolated from the cDNA library of a rat liver. The CYP3A62 cDNA was 1746 base pairs (bp) in length, which included 1491 bp of an open reading frame and 93 bp and 209 bp of the respective 5'- and 3'-noncoding regions. Amino acid sequence deduced from CYP3A62 cDNA shared the highest similarity with rat CYP3A9 (79.9%) among human and rat CYP3A forms previously reported. CYP3A62 mRNA and protein were consistently detected in small intestines as well as livers. CYP3A62 was a major form in small intestines of both sexes but was a female-predominant form in livers of adult rats. CYP3A62 in both tissues of male and female rats were clearly enhanced by the treatment with dexamethasone. These expression profiles resembled those of CYP3A9. Despite clear detection of CYP3A62, no detectable levels of CYP3A1 and CYP3A2 proteins, as well as those of mRNAs, were found in the intestinal tract. Therefore, CYP3A62 may play major roles together with CYP3A9 and CYP3A18 in endogenous or exogenous detoxification at the absorption site.

Isolation and Characterization of a New Major Intestinal CYP3A Form, CYP3A62, in the Rat

Administration of the antibacterial drug ampicillin (ABPC) significantly increased hepatic bile acid concentrations. In the present study, we investigated the mechanisms for the elevation of bile acid levels in ABPC-treated mice. Hepatic microsomal cholesterol 7alpha-hydroxylation and CYP7A1 mRNA level were increased 2.0-fold in ABPC-treated mice despite higher bile acid levels in the liver and small intestinal lumen. A significant change in hepatic small heterodimer partner (SHP) mRNA level was not observed in ABPC-treated mice, whereas a marked decrease in ileal fibroblast growth factor 15 (FGF15) mRNA level was observed (3% of vehicle-treated mice). These phenomena were also observed in mice cotreated with bacitracin/streptomycin/neomycin, which are barely absorbed from the intestine. Primary bile acid contents in the small intestinal lumen were increased in ABPC-treated mice, whereas secondary bile acid, deoxycholic acid (DCA), contents were reduced to below detection limits (<0.01 micromol). In ABPC-treated mice, cotreatment with tauroDCA reversed reductions in ileal FGF15 mRNA level. Ileal SHP mRNA level was, however, not decreased in ABPC-treated mice. ABPC administration to farnesoid X receptor (Fxr)-null mice also decreased ileal FGF15 mRNA levels and secondary bile acid content in the small intestinal lumen. These results suggest that ABPC administration elevates hepatic primary bile acid synthesis, at least in part, through suppression of ileal FGF15 expression.

Masaaki Miyata

Papers

Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity.

Mechanism of 7,12-dimethylbenz[a]anthracene-induced immunotoxicity: role of metabolic activation at the target organ.

Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin.

Isolation and Characterization of a New Major Intestinal CYP3A Form, CYP3A62, in the Rat

Administration of Ampicillin Elevates Hepatic Primary Bile Acid Synthesis through Suppression of Ileal Fibroblast Growth Factor 15 Expression