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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. Highlights • We identified nominally significant associations between arsenic exposure and the relative abundances of several bacterial taxa in the phylum Tenericutes , Proteobacteria , and Firmicutes. However, none of the associations retained significance after correction for multiple comparisons with FDR ≤ 5%. • The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with carotid IMT after adjustment for multiple comparisons with FDR ≤ 5%. • There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P -value = 0.04). • The data suggest that the gut microbiome may play an important role in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dietary pattern analysis is emerging as a practical, effective tool for relating comprehensive dietary intake to risk of cardiovascular disease mortality. However, no studies have applied this technique to a population outside of the developed world. Methods: We conducted prospective cohort analyses in 11,116 participants enrolled in the Health Effects of Arsenic Study in Araihazar, Bangladesh, measuring deaths attributable to disease of circulatory system, heart disease, and cerebrovascular disease. Participants were enrolled in 2000 and followed up for an average of 6.6years. Dietary information was obtained through a previously validated food-frequency questionnaire at baseline. Results: Principal component analysis based on our comprehensive, 39 item FFQ yielded 3 dietary patterns: (i) a “balanced” pattern, comprised of steamed rice, red meat, fish, fruit and vegetables; (ii) an “animal protein” diet, which was more heavily weighted towards eggs, milk, red meat, poultry, bread, and vegetables; and (iii) a “gourd and root vegetable” diet that heavily relied on a variety of gourds, radishes, pumpkin, sweet potato, and spinach. We observed a positive association between increasing adherence to the animal protein diet and risk of death from both disease of the circulatory system and heart disease; the hazard ratios were 1.13 (95% CI, 1.00–1.28, p =0.05) and 1.17 (95% CI, 0.99–1.38, p =0.07), respectively, in relation to one standard deviation increase in the factor scores for the animal protein diet pattern, after controlling for age, sex, body mass index, smoking status, and energy intake. The positive association was more significant among ever smokers; the hazard ratios (95% CI) for deaths from disease of the circulatory system and heart disease were 1.17 (1.02–1.34) and 1.20 (1.00–1.45), respectively, in relation to one standard deviation increase in the factor scores for the animal protein diet pattern. Conclusions: An animal protein-rich diet in rural Bangladesh may increase risk of heart disease mortality, especially among smokers. This emphasizes the need to further explore and address the impact of dietary patterns on cardiovascular disease in populations undergoing epidemiologic transition. [Copyright &y& Elsevier]

• Early childhood is a critical period for telomere biology. • Prior studies of urinary As and telomere length in children have had mixed findings. • We examined urinary As and telomere length in 5–7 year old Bangladeshi children. • Urinary As was associated with significant decreases in relative telomere length. • Arsenic exposure may be related to telomere shortening in early to mid-childhood. Telomere length has been associated with the occurrence and progression of common chronic and age-related diseases, and in younger populations, may represent a biomarker of disease susceptibility. Early childhood is a critical period for telomere biology as this period is characterized by a rapid decline in telomere length due to a large turnover of highly proliferative cells and may represent a period of unique sensitivity to environmental insults. Arsenic (As) exposure has been associated with both telomere lengthening and shortening in adults and children and some evidence suggests the effects may differ by level and timing of exposure. Given the lack of clarity across studies, we investigated the association between urinary As and leukocyte telomere length among 476 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. In a series of multivariable models, adjusted for key covariates, we examined associations between urinary As and relative telomere length (RTL) of whole blood DNA. We observed small but consistent, negative associations between urinary As and RTL, such that a doubling of urinary As was associated with a −0.017 (95% CI: −0.030, −0.005; p = 0.0056) decrease in RTL, in fully adjusted models. We also observed a somewhat stronger inverse relationship between urinary As concentration and RTL among children born to fathers ≥ 30 years of age at the time of birth, than those < 30 years; however, we did not observe a statistically significant interaction. Our study suggests that As influences RTL, with detectable associations in early to mid-childhood. Further studies are needed to confirm our findings and investigate the potential long-term impacts of telomere shortening in childhood on later life health outcomes. Additional studies exploring how dose and timing of exposure may relate to RTL are critical to understanding As's relationship to telomere length. [ABSTRACT FROM AUTHOR]