Abstract
Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
Original language | English |
---|---|
Article number | 100993 |
Journal | Cell Reports Medicine |
Volume | 4 |
Issue number | 4 |
DOIs | |
Publication status | Published - 18 Apr 2023 |
Keywords
- bariatric surgery
- bile acids
- liver function
- post-prandial
- triglycerides
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In: Cell Reports Medicine, Vol. 4, No. 4, 100993, 18.04.2023.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery
AU - Louca, Panayiotis
AU - Meijnikman, Abraham S.
AU - Nogal, Ana
AU - Asnicar, Francesco
AU - Attaye, Ilias
AU - Vijay, Amrita
AU - Kouraki, Afroditi
AU - Visconti, Alessia
AU - Wong, Kari
AU - Berry, Sarah E.
AU - Leeming, Emily R.
AU - Mompeo, Olatz
AU - Tettamanzi, Francesca
AU - Baleanu, Andrei-Florin
AU - Falchi, Mario
AU - Hadjigeorgiou, George
AU - Wolf, Jonathan
AU - Acherman, Yair I. Z.
AU - van de Laar, Arnold W.
AU - Gerdes, Victor E. A.
AU - Michelotti, Gregory A.
AU - Franks, Paul W.
AU - Segata, Nicola
AU - Mangino, Massimo
AU - Spector, Tim D.
AU - Bulsiewicz, William J.
AU - Nieuwdorp, Max
AU - Valdes, Ana M.
AU - Menni, Cristina
N1 - Funding Information: We express our sincere thanks to all the participants of the TwinsUK, ZOE-PREDICT-1, and BARIA studies, including those that devoted their time to the dietary intervention trial. We thank the staff working on each of the cohorts, and Zoe Global, Ltd. for their tireless work in contributing to the running of the study and data collection. This research was funded in whole, or in part, by the Wellcome Trust (WT212904/Z/18/Z). This work was also supported by UKRI grant (MR/W026813/1) to C.M. and A.M.V. For the purpose of open access, the authors have applied a CC BY public copyright to any author accepted manuscript version arising from this submission. The Department of Twin Research receives support from grants from the Wellcome Trust (212904/Z/18/Z) and the Medical Research Council (MRC)/British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1); the European Union; the Chronic Disease Research Foundation (CDRF); Zoe Global, Ltd.; and the NIHR Clinical Research Facility and Biomedical Research Center (based at Guy's and St Thomas’ NHS Foundation Trust in partnership with King's College London). C.M. is funded by the Chronic Disease Research Foundation (CDRF) and by the MRC Aim-Hy project grant. A.M.V. is supported by the National Institutes of Health Research Nottingham Biomedical Research Center. P.L. is funded by the CDRF (CDRF–15/2018). M.N. is supported by a ZonMw VICI grant 2020 (no. 09150182010020) and an NNF GUTMMM grant 2016 NNF15OC0016798 (on which A.S.M. is appointed). I.A. is supported by an Amsterdam UMC postdoc ACS grant. Conceived and designed the experiments, T.D.S. M.N. A.M.V. and C.M.; contributed reagents/materials/analysis tools, A. Vijay, A.K. K.W. E.R.L. F.T. O.M. S.E.B. M.F. G.H. J.W. Y.I.Z.A. A.W.V.d.L. V.E.A.G. G.A.M. and P.W.F.; data curation, F.A. A. Visconti, A. Vijay, N.S. A.S.M. and I.A.; formal analysis, P.L. A.N. M.M. A.M.V. and C.M.; wrote the manuscript, P.L. A.N. W.J.B. A.M.V. and C.M; revised the manuscript, all authors. T.D.S. is co-founder and shareholder of ZOE, Ltd. A.M.V. S.E.B. E.R.L. W.J.B. and P.W.F. are consultants to ZOE, Ltd (“Zoe”). J.W. and G.H. are employees of Zoe. M.N. is a member of the scientific advisory board of Caelus Health; however, this has no direct conflicts of interest with the current paper content. K.W. and G.A.M. are employees of Metabolon, Inc. Funding Information: We express our sincere thanks to all the participants of the TwinsUK, ZOE-PREDICT-1, and BARIA studies, including those that devoted their time to the dietary intervention trial. We thank the staff working on each of the cohorts, and Zoe Global, Ltd., for their tireless work in contributing to the running of the study and data collection. This research was funded in whole, or in part, by the Wellcome Trust ( WT212904/Z/18/Z ). This work was also supported by UKRI grant ( MR/W026813/1 ) to C.M. and A.M.V. For the purpose of open access, the authors have applied a CC BY public copyright to any author accepted manuscript version arising from this submission. The Department of Twin Research receives support from grants from the Wellcome Trust ( 212904/Z/18/Z ) and the Medical Research Council (MRC)/ British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension ( AIM-HY; MR/M016560/1 ); the European Union ; the Chronic Disease Research Foundation (CDRF); Zoe Global, Ltd. ; and the NIHR Clinical Research Facility and Biomedical Research Center (based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London). C.M. is funded by the Chronic Disease Research Foundation (CDRF) and by the MRC Aim-Hy project grant. A.M.V. is supported by the National Institutes of Health Research Nottingham Biomedical Research Center. P.L. is funded by the CDRF ( CDRF–15/2018 ). M.N. is supported by a ZonMw VICI grant 2020 (no. 09150182010020 ) and an NNF GUTMMM grant 2016 NNF15OC0016798 (on which A.S.M. is appointed). I.A. is supported by an Amsterdam UMC postdoc ACS grant. Publisher Copyright: © 2023 The Authors
PY - 2023/4/18
Y1 - 2023/4/18
N2 - Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
AB - Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
KW - bariatric surgery
KW - bile acids
KW - liver function
KW - post-prandial
KW - triglycerides
UR - http://www.scopus.com/inward/record.url?scp=85152733309&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.xcrm.2023.100993
DO - https://doi.org/10.1016/j.xcrm.2023.100993
M3 - Article
C2 - 37023745
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 4
M1 - 100993
ER -