Arsenic exposure and intestinal microbiota in children from Sirajdikhan, Bangladesh.

BACKGROUND: Arsenic has antimicrobial properties at high doses yet few studies have examined its effect on gut microbiota. This warrants investigation since arsenic exposure increases the risk of many diseases in which gut microbiota have been shown to play a role. We examined the association between arsenic exposure from drinking water and the composition of intestinal microbiota in children exposed to low and high arsenic levels during prenatal development and early life. RESULTS: 16S rRNA gene sequencing revealed that children with high arsenic exposure had a higher abundance of Proteobacteria in their stool compared to matched controls with low arsenic exposure. Furthermore, whole metagenome shotgun sequencing identified 332 bacterial SEED functions that were enriched in the high exposure group. A separate model showed that these genes, which included genes involved in virulence and multidrug resistance, were positively correlated with arsenic concentration within the group of children in the high arsenic group. We performed reference free genome assembly, and identified strains of E.coli as contributors to the arsenic enriched SEED functions. Further genome annotation of the E.coli genome revealed two strains containing two different arsenic resistance operons that are not present in the gut microbiome of a recently described European human cohort (Metagenomics of the Human Intestinal Tract, MetaHIT). We then performed quantification by qPCR of two arsenic resistant genes (ArsB, ArsC). We observed that the expression of these two operons was higher among the children with high arsenic exposure compared to matched controls. CONCLUSIONS: This preliminary study indicates that arsenic exposure early in life was associated with altered gut microbiota in Bangladeshi children. The enrichment of E.coli arsenic resistance genes in the high exposure group provides an insight into the possible mechanisms of how this toxic compound could affect gut microbiota.

A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women.

BACKGROUND: In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. METHODS: We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association between anemia and arsenic-induced skin lesions. RESULTS: We observed that the odds of arsenic-related skin lesions were approximately three times higher among women who were anemic (hemoglobin < 120 g/L) compared to women with normal hemoglobin levels [Odds Ratio (OR) = 3.32, 95% Confidence Intervals (CI): 1.29, 8.52] after adjusting for arsenic levels in drinking water and other covariates. Furthermore, 75% of the women with anemia had adequate iron stores (serum ferritin ≥ 12 µg/L), suggesting that the majority of anemia detected in this population was unrelated to iron depletion. CONCLUSIONS: Considering the magnitude of arsenic exposure and prevalence of anemia in Bangladeshi women, additional research is warranted that identifies the causes of anemia so that effective interventions can be implemented while arsenic remediation efforts continue.

Estimating Effects of Arsenic Exposure During Pregnancy on Perinatal Outcomes in a Bangladeshi Cohort.

BACKGROUND: The relationship between arsenic and birth weight is not well understood. The objective was to evaluate the causal relationship between prenatal arsenic exposure and birth weight considering the potential mediation effects of gestational age and maternal weight gain during pregnancy using structural equation models. METHODS: A prospectively enrolled cohort of pregnant women was recruited in Bangladesh from 2008 to 2011. Arsenic was measured in personal drinking water at the time of enrollment (gestational age <16 weeks, N = 1,140) and in toenails collected ≤1 month postpartum (N = 624) using inductively coupled plasma mass spectrometry. Structural equation models estimated the direct and indirect effects of arsenic on birth weight with gestational age and maternal weight gain considered as mediating variables. RESULTS: Every unit increase in natural log water arsenic was indirectly associated with decreased birth weight (ß = -19.17 g, 95% confidence interval [CI]: -24.64, -13.69) after adjusting for other risk factors. This association was mediated entirely through gestational age (ß = -17.37 g, 95% CI: -22.77, -11.98) and maternal weight gain during pregnancy (ß = -1.80 g, 95% CI: -3.72, 0.13). When exposure was modeled using toenail arsenic concentrations, similar results were observed. Every increase in natural log toenail arsenic was indirectly associated with decreased birth weight (ß = -15.72 g, 95% CI: -24.52, -6.91) which was mediated through gestational age (ß = -13.59 g, 95% CI: -22.10, -5.07) and maternal weight gain during pregnancy (ß = -2.13 g, 95% CI: -5.24, 0.96). CONCLUSION: Arsenic exposure during pregnancy was associated with lower birth weight. The effect of arsenic on birth weight appears to be mediated mainly through decreasing gestational age and to a lesser extent by lower maternal weight gain during pregnancy.

A prospective cohort study of the association between drinking water arsenic exposure and self-reported maternal health symptoms during pregnancy in Bangladesh.

BACKGROUND: Arsenic, a common groundwater pollutant, is associated with adverse reproductive health but few studies have examined its effect on maternal health. METHODS: A prospective cohort was recruited in Bangladesh from 2008-2011 (N = 1,458). At enrollment (<16 weeks gestational age [WGA]), arsenic was measured in personal drinking water using inductively-coupled plasma mass spectrometry. Questionnaires collected health data at enrollment, at 28 WGA, and within one month of delivery. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CI) for self-reported health symptoms were estimated for each arsenic quartile using logistic regression. RESULTS: Overall, the mean concentration of arsenic was 38 µg/L (Standard deviation, 92.7 µg/L). A total of 795 women reported one or more of the following symptoms during pregnancy (cold/flu/infection, nausea/vomiting, abdominal cramping, headache, vaginal bleeding, or swollen ankles). Compared to participants exposed to the lowest quartile of arsenic (≤0.9 µg/L), the aOR for reporting any symptom during pregnancy was 0.62 (95% CI = 0.44-0.88) in the second quartile, 1.83 (95% CI = 1.25-2.69) in the third quartile, and 2.11 (95% CI = 1.42-3.13) in the fourth quartile where the mean arsenic concentration in each quartile was 1.5 µg/L, 12.0 µg/L and 144.7 µg/L, respectively. Upon examining individual symptoms, only nausea/vomiting and abdominal cramping showed consistent associations with arsenic exposure. The odds of self-reported nausea/vomiting was 0.98 (95% CI: 0.68, 1.41), 1.52 (95% CI: 1.05, 2.18), and 1.81 (95% CI: 1.26, 2.60) in the second, third and fourth quartile of arsenic relative to the lowest quartile after adjusting for age, body mass index, second-hand tobacco smoke exposure, educational status, parity, anemia, ferritin, medication usage, type of sanitation at home, and household income. A positive trend was also observed for abdominal cramping (P for trend <0.0001). A marginal negative association was observed between arsenic quartiles and odds of self-reported cold/flu/infection (P for trend = 0.08). No association was observed between arsenic and self-reported headache (P for trend = 0.19). CONCLUSION: Moderate exposure to arsenic contaminated drinking water early in pregnancy was associated with increased odds of experiencing nausea/vomiting and abdominal cramping. Preventing exposure to arsenic contaminated drinking water during pregnancy could improve maternal health.