Metabolism of lithocholic acid in the rat: formation of lithocholic acid 3-O-glucuronide in vivo.

Little, Joanna M.; Zimniak, Piotr; Shattuck, Karen E.; Lester, Roger; Radominska, Anna

doi:10.1016/s0022-2275(20)42829-9

Cited by 13 publications

(1 citation statement)

References 32 publications

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“…IsoHDCA is a 3β epimer of HDCA via 3β-epimerization [ 54 ]. For CDCA, it has been demonstrated along the following pathways: CDCA→LCA [ 55 ], CDCA→UDCA [ 56 ], UDCA→LCA [ 57 ], LCA→DHLCA [ 58 ], and UDCA→isoUDCA [ 59 ]. In addition, based on the structural characteristics of BAs, we speculate that the BA metabolism pathways that occur in the rumen may be as follows.…”

Section: Resultsmentioning

confidence: 99%

Rumen microbiome-driven insight into bile acid metabolism and host metabolic regulation

Zhang,

Jiang,

et al. 2024

The ISME Journal

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Gut microbes play a crucial role in transforming primary bile acids (BAs) into secondary forms, which influence systemic metabolic processes. The rumen, a distinctive and critical microbial habitat in ruminants, boasts a diverse array of microbial species with multifaceted metabolic capabilities. There remains a gap in our understanding of BA metabolism within this ecosystem. Herein, through the analysis of 9371 metagenome-assembled genomes and 329 cultured organisms from the rumen, we identified two enzymes integral to BA metabolism: 3-dehydro-bile acid delta4,6-reductase (baiN) and the bile acid:Na + symporter family (BASS). Both in vitro and in vivo experiments were employed by introducing exogenous BAs. We revealed a transformation of BAs in rumen and found an enzyme cluster, including L-ribulose-5-phosphate 3-epimerase and dihydroorotate dehydrogenase. This cluster, distinct from the previously known BA-inducible operon responsible for 7α-dehydroxylation, suggests a previously unrecognized pathway potentially converting primary BAs into secondary BAs. Moreover, our in vivo experiments indicated that microbial BA administration in the rumen can modulate amino acid and lipid metabolism, with systemic impacts underscored by core secondary BAs and their metabolites. Our study provides insights into the rumen microbiome’s role in BA metabolism, revealing a complex microbial pathway for BA biotransformation and its subsequent effect on host metabolic pathways, including those for glucose, amino acids, and lipids. This research not only advances our understanding of microbial BA metabolism but also underscores its wider implications for metabolic regulation, offering opportunities for improving animal and potentially human health.

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Section: Resultsmentioning

confidence: 99%

Rumen microbiome-driven insight into bile acid metabolism and host metabolic regulation

Zhang,

Jiang,

et al. 2024

The ISME Journal

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Lithocholic Acid

2013

Handbook of Metabolic Pathways of Xenobiotics

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Glucuronidation of bile acids by their high-dose infusion into rats

et al. 1991

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We previously reported that high-dose infusion of ursodeoxycholate into rats caused its extensive glucuronidation. In this study, the glucuronidation of various bile acids after high-dose infusion into rats was examined and the effects of coinfusion of bile acids on the glucuronidation of a trace dose of [14C]deoxycholate were also studied. Sixty minutes after infusion of 14C-bile acids at a rate of 1 mumol/min/100 gm, the glucuronidation of the labeled bile acid in the bile was 31%, 15%, 8% and 3% for deoxycholate, ursodeoxycholate, chenodeoxycholate and cholate, respectively. The infusion of a trace dose of [14C] deoxycholate resulted in only 2% glucuronidation, and coinfusion of taurochenodeoxycholate or tauroursodeoxycholate at a rate of 1 mumol/min/100 gm did not change the percentage of glucuronidation of [14C]deoxycholate. However, coinfusion of chenodeoxycholate, ursodeoxycholate or cholate at the same rate markedly increased the percentage of the [14C]deoxycholate-glycuronide in the bile (35%, 18% and 36%, respectively). Thus glucuronidation of bile acids by high-dose infusion into rats occurs predominantly with deoxycholate and is not specific for ursodeoxycholate, and glucuronidation depends on the unconjugated bile acid load, which might be regulated by the capacity of amidation by the liver.

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Metabolism of lithocholic acid in the rat: formation of lithocholic acid 3-O-glucuronide in vivo.

Cited by 13 publications

References 32 publications

Rumen microbiome-driven insight into bile acid metabolism and host metabolic regulation

Rumen microbiome-driven insight into bile acid metabolism and host metabolic regulation

Lithocholic Acid

Glucuronidation of bile acids by their high-dose infusion into rats

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