Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species

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Petersen , A Ø , Julienne , H , Hyötyläinen , T , Sen , P , Fan , Y , Pedersen , H K , Jäntti , S , Hansen , T H , Nielsen , T , Jørgensen , T , Hansen , T , Myers , P N , Nielsen , H B , Ehrlich , S D , Orešič , M & Pedersen , O 2021 , ' Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species ' , Scientific Reports , vol. 11 , no. 1 , 13252 . https://doi.org/10.1038/s41598-021-91482-y

Titel: Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species
Författare: Petersen, Anders Ø.; Julienne, Hanna; Hyötyläinen, Tuulia; Sen, Partho; Fan, Yong; Pedersen, Helle Krogh; Jäntti, Sirkku; Hansen, Tue H.; Nielsen, Trine; Jørgensen, Torben; Hansen, Torben; Myers, Pernille Neve; Nielsen, H. Bjørn; Ehrlich, S. Dusko; Orešič, Matej; Pedersen, Oluf
Upphovmannens organisation: Division of Pharmaceutical Chemistry and Technology
Drug Research Program
Datum: 2021-06-24
Språk: eng
Sidantal: 11
Tillhör serie: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-021-91482-y
Permanenta länken (URI): http://hdl.handle.net/10138/332796
Abstrakt: Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.
Subject: MICROBIOME
RECEPTOR
SAMPLES
IMPACT
BLOOD
317 Pharmacy
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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