Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes : a cohort study
Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism.
OBJECTIVES: We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).
METHODS: A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped.
RESULTS: During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D.
CONCLUSIONS: A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
The American journal of clinical nutrition - 119(2024), 2 vom: 03. Feb., Seite 324-332 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lu, Qi [VerfasserIn] |
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| Links: |
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| Themen: |
Bile Acids and Salts |
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| Anmerkungen: |
Date Completed 05.02.2024 Date Revised 05.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ajcnut.2023.08.023 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367993082 |
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| 100 | 1 | |a Lu, Qi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes |b a cohort study |
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| 500 | |a Date Revised 05.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism | ||
| 520 | |a OBJECTIVES: We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D) | ||
| 520 | |a METHODS: A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped | ||
| 520 | |a RESULTS: During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D | ||
| 520 | |a CONCLUSIONS: A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cardiovascular disease | |
| 650 | 4 | |a polymorphisms | |
| 650 | 4 | |a prospective study | |
| 650 | 4 | |a secondary bile acids | |
| 650 | 4 | |a type 2 diabetes | |
| 650 | 7 | |a Bile Acids and Salts |2 NLM | |
| 700 | 1 | |a Chen, Junxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Limiao |e verfasserin |4 aut | |
| 700 | 1 | |a Geng, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Shufan |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Yunfei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Meian |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Huiru |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, An |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Gang |e verfasserin |4 aut | |
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