Investigation of endogenous metabolic changes in the urine of pseudo germ-free rats using a metabolomic approach

Lee, Soo Hyun; An, Ji Hye; Park, Hyun‐Mee; Jung, Byung Hwa

doi:10.1016/j.jchromb.2011.12.030

Cited by 26 publications

(19 citation statements)

References 71 publications

(82 reference statements)

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“…Much research has reported that hosts without intestinal microflora display altered levels of vitamins, minerals and other nutrients, compared with the normal condition [30][31][32]. Moreover, the metabolomic study on the same animal model by our group has already revealed that the urinary level of pyridoxine 5'-phosphate, a metabolite of vitamin B6, decreased in pseudo germ-free rats [33]. The reduced concentration of pyridoxine 5 0 -phosphate can reflect an alteration of the vitamin B6 pool.…”

Section: Discussionmentioning

confidence: 83%

Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ‐free rats

Lee

et al. 2012

Biopharm & Drug Disp

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To evaluate the metabolic interaction between host and gut microflora on drug metabolism, pseudo germ-free rats were prepared with an antibiotics cocktail to change their gut conditions. The usefulness of the pseudo germ-free model was evaluated for observing the DMPK of acetaminophen (APAP). Pseudo germ-free rats were prepared by orally administering antibiotic cocktails consisting of bacitracin, streptomycin and neomycin, and then APAP was orally administered to control and pseudo germ-free rats. The plasma concentration of APAP and its six metabolites were quantified using a validated LC-MS/MS method. A non-compartment model estimated the pharmacokinetic parameters of APAP and its metabolites, and the ratios of the area under curve (AUC; AUC(metabolite) /AUC(APAP) ) were also observed to evaluate the change of APAP metabolism. The AUCs of APAP and APAP-Glth (glutathione) were higher and the AUC(APAP-Sul) /AUC(APAP) (metabolic efficiency of sulfate conjugation) was lower in pseudo germ-free rats than those in the control rats. The decrease in metabolic efficiency of sulphate conjugation could result from the reduction of the sulphate supply, causing an increase of the AUC of APAP and APAP-Glth. The activities of gut microflora can affect the state of hepatic sulphate for drug conjugation, indirectly leading to characteristic APAP metabolism. These results indicate that gut microflora may play an important role in the pharmacokinetics and metabolism of APAP. Thus, the metabolic interaction between host and gut microflora should be considered upon drug administration and pseudo germ-free rats prepared in the present study can be competent for investigating the metabolic interaction between host and gut microflora on drug metabolism.

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Section: Discussionmentioning

confidence: 83%

Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ‐free rats

Lee

et al. 2012

Biopharm & Drug Disp

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“…Many more colonderived solutes have been identified in rats and mice in which suppression of microbial solute production is easier to accomplish. Studies in these species have identified at least 27 colon-derived solutes which are normally excreted in the urine and/or accumulate in the plasma when kidney function is reduced (Supplemental Table 5) (1,(22)(23)(24)(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Colon-Derived Uremic Solutes

Mair

Sirich

Plummer

et al. 2018

CJASN

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“…1). The reported isoflavone metabolites were utilized for various metabolomic studies to investigate correlations among host physiology, host metabolism, and gut microbiota changes (Lee et al 2012;Kobayashi et al 2013). The genes involved in the biotransformation of daidzein and the metabolites were also cloned from the isolated intestinal bacteria for the biochemical research (Shimada et al 2010;Tsuji et al 2012;Schröder et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Deglycosylation of flavonoid O-glucosides by human intestinal bacteria Enterococcus sp. MRG-2 and Lactococcus sp. MRG-IF-4

Kim

Han

2016

Appl Biol Chem

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Daidzin, daidzein 7-O-glucoside, is a major isoflavone in soybean and acts as a phytoestrogen. By intestinal bacteria dietary, daidzin is hydrolyzed to the aglycone daidzein and further converted to the more reduced metabolites, such as dihydrodaidzein, tetrahydrodaidzein, and equol. Human intestinal bacteria Enterococcus sp. MRG-2 and Lactococcus sp. MRG-IF-4, which convert daidzin to daidzein, were isolated under anaerobic condition, and identified by 16S rRNA gene sequence analysis. Changes of OD 600 and pH were measured during the anaerobic growth, and deglycosylation kinetics of daidzin and genistin were measured by HPLC. Both bacteria also converted other isoflavone 7-O-glucosides, glycitin, ononin, and sissotrin, to their aglycones, glycitein, formononetin, and biochanin A, respectively. Apigetrin was deglycosylated to apigenin by these bacteria too. However, rutin, hesperidin, and naringin were not converted to the aglycones. Phylogeny analysis of the isolated strains also found that bacterial species identified by 16S rRNA gene sequence was not correlated with its metabolic ability of flavonoid biotransformation.

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Investigation of endogenous metabolic changes in the urine of pseudo germ-free rats using a metabolomic approach

Cited by 26 publications

References 71 publications

Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ‐free rats

Evaluation of pharmacokinetic differences of acetaminophen in pseudo germ‐free rats

Characteristics of Colon-Derived Uremic Solutes

Deglycosylation of flavonoid O-glucosides by human intestinal bacteria Enterococcus sp. MRG-2 and Lactococcus sp. MRG-IF-4

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