PMID- 31818878 OWN - NLM STAT- MEDLINE DCOM- 20210208 LR - 20220514 IS - 1539-7262 (Electronic) IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 61 IP - 2 DP - 2020 Feb TI - Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases. PG - 159-177 LID - 10.1194/jlr.RA119000311 [doi] AB - Bile acids (BAs) serve multiple biological functions, ranging from the absorption of lipids and fat-soluble vitamins to serving as signaling molecules through the direct activation of dedicated cellular receptors. Synthesized by both host and microbial pathways, BAs are increasingly understood as participating in the regulation of numerous pathways relevant to metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Quantitative analyses of BAs in biological matrices can be problematic due to their unusual and diverse physicochemical properties, making optimization of a method that shows good accuracy, precision, efficiency of extraction, and minimized matrix effects across structurally distinct human and murine BAs challenging. Herein we develop and clinically validate a stable-isotope-dilution LC/MS/MS method for the quantitative analysis of numerous primary and secondary BAs in both human and mouse biological matrices. We also utilize this tool to investigate gut microbiota participation in the generation of structurally specific BAs in both humans and mice. We examine circulating levels of specific BAs and in a clinical case-control study of age- and gender-matched type 2 diabetes mellitus (T2DM) versus nondiabetics. BAs whose circulating levels are associated with T2DM include numerous 12alpha-hydroxyl BAs (taurocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid, and 3-ketodeoxycholic acid), while taurohyodeoxycholic acid was negatively associated with diabetes. The LC/MS/MS-based platform described should serve as a robust, high-throughput investigative tool for studying the potential involvement of structurally specific BAs and the gut microbiome on both physiological and disease processes. CI - Copyright (c) 2020 Choucair et al. FAU - Choucair, Ibrahim AU - Choucair I AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. FAU - Nemet, Ina AU - Nemet I AUID- ORCID: 0000-0002-0657-7121 AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195 nemeti@ccf.org. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. FAU - Li, Lin AU - Li L AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. FAU - Cole, Margaret A AU - Cole MA AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. FAU - Skye, Sarah M AU - Skye SM AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. FAU - Kirsop, Jennifer D AU - Kirsop JD AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. FAU - Fischbach, Michael A AU - Fischbach MA AUID- ORCID: 0000-0003-3079-8247 AD - Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305. FAU - Gogonea, Valentin AU - Gogonea V AUID- ORCID: 0000-0002-6154-8497 AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. AD - Department of Chemistry, Cleveland State University, Cleveland, OH 44115. FAU - Brown, J Mark AU - Brown JM AUID- ORCID: 0000-0003-2708-7487 AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. FAU - Tang, W H Wilson AU - Tang WHW AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. AD - Lerner Research Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195. FAU - Hazen, Stanley L AU - Hazen SL AUID- ORCID: 0000-0001-7124-6639 AD - Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195. AD - Heart and Vascular Institute, and Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195. AD - Lerner Research Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195. LA - eng GR - R01 DK120679/DK/NIDDK NIH HHS/United States GR - P01 HL147823/HL/NHLBI NIH HHS/United States GR - R01 HL103866/HL/NHLBI NIH HHS/United States GR - R01 HL126827/HL/NHLBI NIH HHS/United States GR - P50 AA024333/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20191209 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Bile Acids and Salts) SB - IM MH - Animals MH - Bile Acids and Salts/*analysis/chemistry MH - Case-Control Studies MH - Chromatography, Liquid MH - Diabetes Mellitus, Type 2/*metabolism/microbiology MH - Female MH - *Gastrointestinal Microbiome MH - Healthy Volunteers MH - Humans MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Quality Control MH - Tandem Mass Spectrometry PMC - PMC6997600 OTO - NOTNLM OT - diabetes OT - liquid chromatography OT - steroids COIS- S.L.H. also reports being a paid consultant for P&G, having received research funds from P&G and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, Quest Diagnostics, and P&G. The other authors have reported that they have no relationships relevant to the contents of this article to disclose. EDAT- 2019/12/11 06:00 MHDA- 2021/02/09 06:00 PMCR- 2021/02/01 CRDT- 2019/12/11 06:00 PHST- 2019/08/06 00:00 [received] PHST- 2019/11/24 00:00 [revised] PHST- 2019/12/11 06:00 [pubmed] PHST- 2021/02/09 06:00 [medline] PHST- 2019/12/11 06:00 [entrez] PHST- 2021/02/01 00:00 [pmc-release] AID - S0022-2275(20)43534-5 [pii] AID - rA119000311 [pii] AID - 10.1194/jlr.RA119000311 [doi] PST - ppublish SO - J Lipid Res. 2020 Feb;61(2):159-177. doi: 10.1194/jlr.RA119000311. Epub 2019 Dec 9.