Dataset Information

The role of gut microbiome and its interaction with arsenic exposure in carotid intima-media thickness in a Bangladesh population.

ABSTRACT:

Background

Emerging data suggest that inorganic arsenic exposure and gut microbiome are associated with the risk of cardiovascular disease. The gut microbiome may modify disease risk associated with arsenic exposure. Our aim was to examine the inter-relationships between arsenic exposure, the gut microbiome, and carotid intima-media thickness (IMT)-a surrogate marker for atherosclerosis.

Methods

We recruited 250 participants from the Health Effects of Arsenic Longitudinal Study in Bangladesh, measured IMT and collected fecal samples in year 2015-2016. 16S rRNA gene sequencing was conducted on microbial DNA extracted from the fecal samples. Arsenic exposure was measured using data on arsenic concentration in drinking water wells over time to derive a time-weighted water arsenic index. Multivariable linear regression models were used to test the inter-relationships between arsenic exposure, relative abundance of selected bacterial taxa from phylum to genus levels, and IMT.

Results

We identified nominally significant associations between arsenic exposure, measured using either time-weighted water arsenic or urinary arsenic, and the relative abundances of several bacterial taxa from the phylum Tenericutes, Proteobacteria, and Firmicutes. However, none of the associations retained significance after correction for multiple testing. The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with IMT after correction for multiple testing (P-value = 0.02 and 0.03, respectively). Every 1% increase in the relative abundance of Aeromonadaceae and Citrobacter was related to an 18.2-μm (95% CI: 7.8, 28.5) and 97.3-μm (95% CI: 42.3, 152.3) difference in IMT, respectively. These two taxa were also the only selected family and genus using the LASSO variable selection method. There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P for interaction = 0.04).

Conclusions

Our findings suggest a role of Citrobacter in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure.

SUBMITTER: Wu F

PROVIDER: S-EPMC6371773 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).