Will the real bile acid sulfotransferase please stand up? Identification of Sult2a8 as a major hepatic bile acid sulfonating enzyme in mice

Dawson, Paul A.; Setchell, Kenneth D.R.

doi:10.1194/jlr.c077420

Cited by 15 publications

(11 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Miyata et al have reported that the hepatic sulfotransferase Sult2a1 is negatively regulated through FXR in mice and humans (62). Sult2a8 was recently identified as a major BA-sulfonating enzyme in mice (63). Here, we observed that the expression of Sult2a8 was comparable among the various mouse models, suggesting that Sult2a8 is neither regulated through the FXR nor influenced by the gut microbiota (Fig.…”

Section: Ba Detoxificationsupporting

confidence: 49%

Biogeography of microbial bile acid transformations along the murine gut

Marion

Desharnais

Studer

et al. 2020

Journal of Lipid Research

View full text Add to dashboard Cite

Bile acids, synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota and the products of these transformations signal through host receptors, impacting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, with a dysbiosed microbiota or with no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms able to carry out this process by this compound. Finally, comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.

show abstract

Section: Ba Detoxificationsupporting

confidence: 49%

Biogeography of microbial bile acid transformations along the murine gut

Marion

Desharnais

Studer

et al. 2020

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…The role that CA7S plays in the metabolic changes observed post-SG remains unknown. Due to the redundancy of sulfotransferases (SULTs), the enzymes responsible for hepatic CA7S synthesis 39 , knockdown of endogenous CA7S levels may be challenging. If this obstacle could be overcome, performing SG on CA7S-depleted mice would help reveal the contribution of this molecule to the metabolic effects of the surgery.…”

Section: Discussionmentioning

confidence: 99%

Bariatric surgery reveals a gut-restricted TGR5 agonist with anti-diabetic effects

et al. 2020

View full text Add to dashboard Cite

Bariatric surgery, the most effective treatment for obesity and type 2 diabetes, is associated with increased levels of the incretin hormone GLP-1 and changes in levels of circulating bile acids. The levels of individual bile acids in the GI tract following surgery, however, have remained largely unstudied. Using UPLC-MS-based quantification, we observed an increase in an endogenous bile acid, cholic acid-7-sulfate (CA7S), in the GI tract of both mice and humans after sleeve gastrectomy. We show that CA7S is a TGR5 agonist that increases Tgr5 expression and induces GLP-1 secretion. Further, CA7S administration increases glucose tolerance in insulin-resistant mice in a TGR5-dependent manner. CA7S remains gut-restricted, minimizing off-target effects previously observed for TGR5 agonists absorbed into circulation. By studying changes in individual metabolites following surgery, this study has revealed a naturally occurring TGR5 agonist that exerts systemic glucoregulatory effects while remaining confined to the gut.

show abstract

“…Sulfonation of BAs primarily occurs in the mammalian liver via BA sulfotransferase enzymes or SULTs ( Figure 1H) (Alnouti, 2009). Three isoforms of BA-SULTs have been identified in mice (mSULT2A1, mSULT2A2, and mSULT2A8) and one isoform in humans (hSULT2A) that specifically sulfate BAs (Alnouti, 2009;Dawson and Setchell, 2017;Feng et al, 2017). Post-SG mouse livers exhibited higher expression levels of the mSult2A1 isoform than sham livers, while there were no differences in expression of the mSult2A2 or mSult2A8 isoforms ( Figure 1I, refer Table S1 for all qPCR primer sequences).…”

Section: Production Of Ca7s and Induction Of Glp-1 Requires A Microbiomementioning

confidence: 99%