Characterization of gut microbial structural variations as determinants of human bile acid metabolism

Daoming Wang; Marwah Doestzada; Lianmin Chen; Sergio Andreu-Sánchez; Inge C L van den Munckhof; Hannah E Augustijn; Martijn Koehorst; Angel J Ruiz-Moreno; Vincent W Bloks; Niels P Riksen; Joost H W Rutten; Leo A B Joosten; Mihai G Netea; Cisca Wijmenga; Alexandra Zhernakova; Folkert Kuipers; Jingyuan Fu

doi:10.1016/j.chom.2021.11.003

Characterization of gut microbial structural variations as determinants of human bile acid metabolism

Daoming Wang, Marwah Doestzada, Lianmin Chen, Sergio Andreu-Sánchez, Inge C L van den Munckhof, Hannah E Augustijn, Martijn Koehorst, Angel J Ruiz-Moreno, Vincent W Bloks, Niels P Riksen, Joost H W Rutten, Leo A B Joosten, Mihai G Netea, Cisca Wijmenga, Alexandra Zhernakova, Folkert Kuipers, Jingyuan Fu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host-gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but it remains largely unknown how the highly variable genomes of gut bacteria interact with host BA metabolism. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete clusters showed correlations with BA metabolism. Metagenome-wide association analysis identified 809 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the largest microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and it highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.

Original language	English
Pages (from-to)	1802-1814.e5
Number of pages	13
Journal	Cell Host & Microbe
Volume	29
Issue number	12
Early online date	29-Nov-2021
DOIs	https://doi.org/10.1016/j.chom.2021.11.003
Publication status	Published - Dec-2021

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Wang, D., Doestzada, M., Chen, L., Andreu-Sánchez, S., van den Munckhof, I. C. L., Augustijn, H. E., Koehorst, M., Ruiz-Moreno, A. J., Bloks, V. W., Riksen, N. P., Rutten, J. H. W., Joosten, L. A. B., Netea, M. G., Wijmenga, C., Zhernakova, A., Kuipers, F., & Fu, J. (2021). Characterization of gut microbial structural variations as determinants of human bile acid metabolism. Cell Host & Microbe, 29(12), 1802-1814.e5. https://doi.org/10.1016/j.chom.2021.11.003

@article{cd2555f6ca094efa9b82bbc5fc19daeb,

title = "Characterization of gut microbial structural variations as determinants of human bile acid metabolism",

abstract = "Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host-gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but it remains largely unknown how the highly variable genomes of gut bacteria interact with host BA metabolism. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete clusters showed correlations with BA metabolism. Metagenome-wide association analysis identified 809 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the largest microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and it highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.",

author = "Daoming Wang and Marwah Doestzada and Lianmin Chen and Sergio Andreu-S{\'a}nchez and {van den Munckhof}, {Inge C L} and Augustijn, {Hannah E} and Martijn Koehorst and Ruiz-Moreno, {Angel J} and Bloks, {Vincent W} and Riksen, {Niels P} and Rutten, {Joost H W} and Joosten, {Leo A B} and Netea, {Mihai G} and Cisca Wijmenga and Alexandra Zhernakova and Folkert Kuipers and Jingyuan Fu",

year = "2021",

month = dec,

doi = "10.1016/j.chom.2021.11.003",

language = "English",

volume = "29",

pages = "1802--1814.e5",

journal = "Cell Host & Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "12",

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Wang, D, Doestzada, M, Chen, L, Andreu-Sánchez, S, van den Munckhof, ICL, Augustijn, HE, Koehorst, M, Ruiz-Moreno, AJ, Bloks, VW, Riksen, NP, Rutten, JHW, Joosten, LAB, Netea, MG, Wijmenga, C , Zhernakova, A , Kuipers, F & Fu, J 2021, 'Characterization of gut microbial structural variations as determinants of human bile acid metabolism', Cell Host & Microbe, vol. 29, no. 12, pp. 1802-1814.e5. https://doi.org/10.1016/j.chom.2021.11.003

TY - JOUR

T1 - Characterization of gut microbial structural variations as determinants of human bile acid metabolism

AU - Wang, Daoming

AU - Doestzada, Marwah

AU - Chen, Lianmin

AU - Andreu-Sánchez, Sergio

AU - van den Munckhof, Inge C L

AU - Augustijn, Hannah E

AU - Koehorst, Martijn

AU - Ruiz-Moreno, Angel J

AU - Bloks, Vincent W

AU - Riksen, Niels P

AU - Rutten, Joost H W

AU - Joosten, Leo A B

AU - Netea, Mihai G

AU - Wijmenga, Cisca

AU - Zhernakova, Alexandra

AU - Kuipers, Folkert

AU - Fu, Jingyuan

PY - 2021/12

Y1 - 2021/12

N2 - Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host-gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but it remains largely unknown how the highly variable genomes of gut bacteria interact with host BA metabolism. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete clusters showed correlations with BA metabolism. Metagenome-wide association analysis identified 809 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the largest microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and it highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.

AB - Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host-gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but it remains largely unknown how the highly variable genomes of gut bacteria interact with host BA metabolism. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete clusters showed correlations with BA metabolism. Metagenome-wide association analysis identified 809 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the largest microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and it highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.

U2 - 10.1016/j.chom.2021.11.003

DO - 10.1016/j.chom.2021.11.003

M3 - Article

C2 - 34847370

SN - 1931-3128

VL - 29

SP - 1802-1814.e5

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 12

ER -

Characterization of gut microbial structural variations as determinants of human bile acid metabolism

Abstract

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