The response of gut microbiota to arsenic metabolism is involved in arsenic-induced liver injury, which is influenced by the interaction between arsenic and methionine synthase.

The drivers of changes in gut microbiota under arsenic exposure and the mechanism by which microbiota affect arsenic metabolism are still unclear. Here, C57BL/6 mice were exposed to 0, 5, or 10 ppm NaAsO2 in drinking water for 6 months. The results showed that arsenic exposure induced liver injury and increased the abundance of folic acid (FA)/vitamin B12 (VB12)- and butyrate-synthesizing microbiota. Statistical analysis and in vitro cultures showed that microbiota were altered to meet the demand for FA/VB12 by arsenic metabolism and to resist the toxicity of unmetabolized arsenic. However, at higher arsenic levels, changes of these microbiota were inconsistent. A 3D molecular simulation showed that arsenic bound to methionine synthase (MTR), which was confirmed by SEC-UV-DAD (1 µM recombinant human MTR was purified with 0 or 2 µM NaAsO2 at room temperature for 1 h) and fluorescence-labeled arsenic co-localization (primary hepatocytes were exposed to 0, 0.5, or 1 µM ReAsH-EDT2 for 24 h) in non-cellular and cellular systems. Mechanistically, the arsenic-MTR interaction in the liver interferes with the utilization of FA/VB12, which increases arsenic retention and thus results in a substantial increase in the abundance of butyrate-synthesizing microbiota compared to FA/VB12-synthesizing microbiota. By exposing C57BL/6J mice to 0 or 10 ppm NaAsO2 with or without FA (6 mg/L) and VB12 (50 µg/L) supplementation in their drinking water for 6 months, we constructed an FA/VB12 intervention mouse model and found that FA/VB12 supplementation blocked the disturbance of gut microbiota, restored MTR levels, promoted arsenic metabolism, and alleviated liver injury. We demonstrate that the change of gut microbiota is a response to arsenic metabolism, a process influenced by the arsenic-MTR interaction. This study provides new insights for understanding the relationship between gut microbiota and arsenic metabolism and present therapeutic targets for arseniasis.

Prenatal arsenic metabolite exposure is associated with increased newborn mitochondrial DNA copy number: evidence from a birth cohort study.

While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether maternal urinary arsenic metabolite levels in different trimesters were related to neonatal cord blood mtDNAcn. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters. We determined cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each one-unit increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the third trimester was related to 8.43% (95% CI 1.13%, 16.26%) and 12.15% (95% CI 4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the third trimester with mtDNAcn (DMA percent changes (%Δ) = 25.60 (95% CI 6.73, 47.82), for the highest vs the lowest tertile (P = 0.02); TAs %Δ = 40.31 (95% CI 19.25, 65.10), for the highest vs the lowest tertile (P = 0.0002)). These findings may prove the relationships between prenatal arsenic species levels and neonatal mitochondrial dysfunction.

Novel insights into the co-selection of metal-driven antibiotic resistance in bacteria: a study of arsenic and antibiotic co-exposure.

The simultaneous development of antibiotic resistance in bacteria due to metal exposure poses a significant threat to the environment and human health. This study explored how exposure to both arsenic and antibiotics affects the ability of an arsenite oxidizer, Achromobacter xylosoxidans CAW4, to transform arsenite and its antibiotic resistance patterns. The bacterium was isolated from arsenic-contaminated groundwater in the Chandpur district of Bangladesh. We determined the minimum inhibitory concentration (MIC) of arsenite, cefotaxime, and tetracycline for A. xylosoxidans CAW4, demonstrating a multidrug resistance (MDR) trait. Following this determination, we aimed to mimic an environment where A. xylosoxidans CAW4 was exposed to both arsenite and antibiotics. We enabled the strain to grow in sub-MIC concentrations of 1 mM arsenite, 40 µg/mL cefotaxime, and 20 µg/mL tetracycline. The expression dynamics of the arsenite oxidase (aioA) gene in the presence or absence of antibiotics were analyzed. The findings indicated that simultaneous exposure to arsenite and antibiotics adversely affected the bacteria's capacity to metabolize arsenic. However, when arsenite was present in antibiotics-containing media, it promoted bacterial growth. The study observed a global downregulation of the aioA gene in arsenic-antibiotic conditions, indicating the possibility of increased susceptibility through co-resistance across the entire bacterial population of the environment. This study interprets that bacterial arsenic-metabolizing ability can rescue the bacteria from antibiotic stress, further disseminating environmental cross-resistance. Therefore, the co-selection of metal-driven antibiotic resistance in bacteria highlights the need for effective measures to address this emerging threat to human health and the environment.

Polystyrene microplastic alters the redox state and arsenic metabolization in the freshwater bivalve Limnoperna fortunei.

Most organisms possess the capacity to metabolize arsenic (As) accumulating compounds to less toxic forms, thus minimizing the adverse effect induced by this metalloid. However, other contaminants may to interfere with As metabolism, contributing to the accumulation of more toxic compounds. Microplastics (MPs) are omnipresent in aquatic environment and may induce toxicological effects (alone or in combination with other contaminants) on living organisms. Therefore, the objective of the present study was to evaluate the effect of the exposure of the freshwater clam Limnoperna fortunei to a combination of MP (4 and 40 µg/L of polystyrene microbeads, 1.05 µm) and As (50 µg/L) for 48 h, evaluating the accumulation and metabolization of As and oxidative stress parameters, such as catalase (CAT), glutathione-S-transferase activities, total antioxidant competence, reduced glutathione (GSH), and lipid damage in the gills and digestive glands. Results revealed that low MP concentration disrupts the redox state of the digestive gland by a decrease in the antioxidant activity (CAT and total antioxidant capacity). GSH levels in the gills of animals exposed to MP (4 µg/L) alone and the combination of MP + As increased, concomitant with an increase in the percentage of toxic compounds, indicating the effect of MP on As metabolism. Although, few studies evaluated the effect of coexposure to MP + As by considering metabolization of metalloid in freshwater bivalve, our results revealed that exposure to MP reduced the metabolization capacity of As, favoring the accumulation of more toxic compounds besides the MP alone, which showed a pro-oxidant effect in L. fortunei.

Altered cord blood mitochondrial DNA content and prenatal exposure to arsenic metabolites in low-arsenic areas.

While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether arsenic metabolism in different trimesters was related to cord blood mtDNAcn alteration. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters using HPLC-ICPMS. We decided on cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each two-fold increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the 3rd trimester were related to 8.43% (95% CI: 1.13%, 16.26%) and 12.15% (95% CI:4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the 3rd trimester with mtDNAcn. These findings may prove the relationships between arsenic species and mitochondrial dysfunction.

Urinary arsenic metabolism, genetic susceptibility, and their interaction on type 2 diabetes.

Growing studies investigated the association of arsenic metabolism with type 2 diabetes (T2D), however, the epidemiological evidence is inconsistent. In addition, the interaction of arsenic metabolism-related genetic risk score (GRS)-arsenic on T2D risk was unclear. The present study aimed to evaluate the association of arsenic metabolism efficiency [inorganic arsenic (iAs)%, monomethylarsonic acid (MMA)%, and dimethylarsinic acid (DMA%)] with T2D risk. Moreover, the relationship of GRS and arsenic metabolism efficiency and the interaction of GRS-arsenic on T2D were investigated. Age- and sex-matched new-onset diabetes case-control study derived from the Dongfeng-Tongji cohort was conducted and 996 pairs participants were included in this study. The leave-one-out approach was used to evaluate the association of arsenic metabolism efficiency with T2D risk. The GRS and weight GRS (wGRS) were calculated based on 79 candidate SNPs. We estimated the relationship of GRS with arsenic metabolism efficiency by linear regression model. The interaction of GRS-arsenic on T2D was assessed by adding a multiplicative interaction term (GRS × arsenic) in the logistic regression models. Urinary iAs% was positively associated with T2D risk, and the OR (95% CI) was 1.06 (1.01, 1.12). MMA% and PMI were negatively associated with T2D risk, and the ORs (95% CI) were 0.87 (0.78, 0.97) and 0.64 (0.47, 0.86), respectively. Urinary DMA, As3+, and As5+ were positively associated with T2D risk. Similar relationships were found between arsenic metabolites and levels of FPG and HbA1c. Moreover, arsenic metabolism-related GRS/wGRS was positively associated with MMA% but negatively associated with DMA%. Genetic predisposition to arsenic metabolism modified the association of inorganic arsenic with T2D risk (Pinteraction = 0.033). Taken together, lower arsenic primary metabolism efficiency (higher iAs% and lower MMA%) may increase T2D risk. Genetic predisposition to arsenic metabolism was associated with arsenic metabolism efficiency, and might modify the association of inorganic arsenic with T2D risk.

Association of urinary arsenic metabolism with type 2 diabetes and glucose homeostasis: Cross-sectional and longitudinal associations.

BACKGROUND: Previous researches have assessed the relationships of urinary arsenic metabolism with type 2 diabetes (T2D) and glucose-insulin homeostasis, but the results were controversial, and potential mechanisms remain largely unclear. OBJECTIVES: This study aimed to investigate the cross-sectional and longitudinal associations of urinary arsenic metabolism with T2D prevalence and glucose changes in relatively higher arsenic exposure, and further to evaluate the underlying roles of oxidative damage in these relationships. METHODS: We included 796 participants at baseline, among them 509 participants were followed up after 2 years. Logistic regression model and leave-one-out approach were applied to evaluate the associations of arsenic metabolism with T2D prevalence. Linear mixed model was conducted to estimate the relationship of arsenic metabolism with glycemic changes over two years. The associations between arsenic metabolism and indicators of oxidative stress were assessed with a linear regression model. We further performed mediation analysis to investigate the role of oxidative stress in the associations of arsenic metabolism with 2-year change of glucose levels. RESULTS: Higher urinary MMA% increased T2D prevalence and baseline glucose levels. MMA% was positively associated with 2-year change of glucose levels. Moreover, we observed significant dose-response relationship between MMA% and 8-hydroxy-2-deoxyguanosine (8-OHdG). However, the mediating role of 8-OHdG in the association of MMA% and 2-year change of glucose levels was not observed in this population. CONCLUSIONS: In this population exposure to relatively higher arsenic levels, higher MMA% contributed to increased T2D prevalence and glucose homeostasis disorder. Arsenic metabolism also affected oxidative stress levels, especially 8-OHdG. Further studies are required to investigate the potential mechanisms.

The disruption of blood-brain barrier induced by long-term arsenic exposure is associated with the increase of MMP-9 and MMP-2: The characteristics are similar to those caused by senescence.

Accumulating evidence suggests that Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) are involved in the neuropathological processes by contributing to breaking the extracellular matrix and the tight junctions that constitute the blood-brain barrier (BBB). However, the influences of arsenic (As) on these two MMPs were inconsistent. In the cross-sectional study of 500 adults, serum MMP-2 and MMP-9 positively correlated with urine arsenic. And the positive correlation between urine tAs and serum MMP-9/2 was found in people older than 59 years. In vivo studies, we found that arsenic exposure or senescence might decrease number of neurons and neuritic density and increase serum and cortical MMP-9/2 levels. Furthermore, arsenic exposure or senescence could disrupt the tight junction of BBB and elevate MMP-9 and MMP-2 expression in the cerebral microvascular endothelium. The MMP-9 and MMP-2 are of particular interest when researching the link between arsenic exposure and nerve damage.

Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort.

BACKGROUND: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy. METHODS: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models. RESULTS: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (ß 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele). CONCLUSIONS: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations.

Anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh.

INTRODUCTION: Arsenic methylation converts inorganic arsenic (iAs) to monomethyl (MMA) and dimethyl (DMA) arsenic compounds. Body mass index (BMI) has been positively associated with arsenic methylation efficiency (higher DMA%) in adults, but evidence in pregnancy is inconsistent. We estimated associations between anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh. METHODS: We enrolled pregnant women (n = 784) (median [IQR] gestational week: 14 [13, 15]) in Gaibandha District, Bangladesh from 2018 to 2019. Anthropometric measures were BMI, subscapular and triceps skinfold thicknesses, and mid-upper arm circumference (MUAC), fat area (MUAFA), and muscle area (MUAMA). Arsenic methylation measures were urinary iAs, MMA, and DMA divided by their sum and multiplied by 100 (iAs%, MMA%, and DMA%), primary methylation index (MMA/iAs; PMI), and secondary methylation index (DMA/MMA; SMI). In complete cases (n = 765 [97.6%]), we fitted linear, beta, and Dirichlet regression models to estimate cross-sectional differences in iAs%, MMA%, DMA%, PMI, and SMI per IQR-unit difference in each anthropometric measure, adjusting for drinking water arsenic, age, gestational age, education, living standards index, and plasma folate, vitamin B12, and homocysteine. RESULTS: Median (IQR) BMI, subscapular skinfold thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 21.5 (19.4, 23.8) kg/m2, 17.9 (13.2, 24.2) mm, 14.2 (10.2, 18.7) mm, 25.9 (23.8, 28.0) cm, 15.3 (10.5, 20.3) cm2, and 29.9 (25.6, 34.2) cm2, respectively. Median (IQR) iAs%, MMA%, DMA%, PMI, and SMI were 12.0 (9.3, 15.2)%, 6.6 (5.3, 8.3)%, 81.0 (77.1, 84.6)%, 0.6 (0.4, 0.7), and 12.2 (9.3, 15.7), respectively. In both unadjusted and adjusted linear models, all anthropometric measures were negatively associated with iAs%, MMA%, and PMI and positively associated with DMA% and SMI. For example, fully adjusted mean differences (95% CI) in DMA% per IQR-unit difference in BMI, subscapular skinfolds thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 1.72 (1.16, 2.28), 1.58 (0.95, 2.21), 1.74 (1.11, 2.37), 1.45 (0.85, 2.06), 1.70 (1.08, 2.31), and 0.70 (0.13, 1.27) pp, respectively. CONCLUSIONS: Anthropometric measures were positively associated with arsenic methylation efficiency among pregnant women in the early second trimester.

Type 2 diabetes affects arsenic metabolism via transporters in arsenic trioxide treated acute promyelocytic leukemia patients.

Our study aimed to explore whether type 2 diabetes (T2DM) can affect arsenic metabolism in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide. We found that compared with non-diabetic APL patients, the concentrations of arsenic metabolites in APL patients with T2DM increased significantly and positively correlated with blood glucose (P < 0.05). Meanwhile, APL patients with T2DM were more prone to liver injury and QTc interval prolongation due to altered arsenic methylation capacity. Then we cultured HEK293T cells at different glucose concentrations, and the results showed that the cells with high glucose had higher concentrations of arsenic metabolites compared to other cells. Meanwhile, the high glucose significantly increased the mRNA and protein expression levels of the arsenic uptake transporter AQP7 in HEK293T cells. Overall, our study demonstrated that T2DM can lead to elevated concentrations of arsenic metabolites in APL patients by increasing AQP7 expression.

Prenatal arsenic exposure, arsenic metabolism and neurocognitive development of 2-year-old children in low-arsenic areas.

BACKGROUND: There is limited evidence on the effects of arsenic species and metabolic capacity on child neurodevelopment, particularly at low levels. Further, little is known about the critical window of exposure. OBJECTIVE: To estimate the associations of arsenic exposure and arsenic metabolism in different pregnancy periods with neurodevelopment of two-year-old children. METHODS: Concentrations of arsenobetaine (AsB), arsenite, arsenate, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA) in urine samples collected in three trimesters from 1006 mothers were measured using HPLC - ICPMS. Inorganic arsenic (iAs) was calculated as the sum of arsenite and arsenate. Total arsenic (tAs) was calculated as the sum of iAs, MMA and DMA. Child neurodevelopment was assessed with the Bayley Scales of Infant Development. RESULTS: The geometric mean (GM) of SG-adjusted tAs in the first, second, third trimester was 16.37, 12.94, 13.04 µg/L, respectively. The mental development index (MDI) score was inversely associated with iAs and tAs. Compared to the 1st quartile, the MDI score decreased 0.43 (95%CI: -4.22, 3.36) for the 2nd, 6.50 (95%CI: -11.73, -1.27) for the 3rd, 5.42 (95%CI: -10.74, -0.10) for the 4th quartiles of iAs, and decreased 4.03 (95%CI: -7.90, -0.15) in the 4th quartile of tAs. In trimester-specific models, negative associations of DMA [-1.94 (95%CI: -3.18, -0.71)] and tAs [-1.61 (95%CI: -3.02, -0.20)] with the psychomotor development index (PDI) were only observed in 1st trimester. CONCLUSIONS: Our study found inverse associations between prenatal arsenic exposure, especially in early pregnancy, and neurodevelopment of children at two years old, even at low exposure levels.

Association of arsenic exposure and clinical hematological changes during pregnancy: Findings from a prospective Wuhan birth cohort study.

BACKGROUND: Animal studies have reported arsenic-induced disturbed erythropoiesis parameters. However, the effects of exposure to arsenic on hematological parameters among pregnant women are unclear. OBJECTIVES: We aimed to evaluate trimester-specific associations between arsenic metabolites and erythropoietic parameters measured repeatedly during pregnancy. METHODS: A total of 1945 pregnant women from a birth cohort study were included. We detected arsenic species in urine sampled at each trimester and extracted erythropoietic parameters in different trimesters from the medical records. We used linear regressions with generalized estimating equations (GEEs) to examine the relationship between arsenic metabolites concentrations at different trimesters and erythropoietic parameters. We utilized GEEs to calculate the odds ratio (OR) for anemia during pregnancy. RESULTS: Adjusted trimester-specific analysis showed that higher monomethylated arsenic (MMA) and %MMA were related to remarkably reduced hemoglobin (Hb) and mean corpuscular hemoglobin (MCH). Additionally, elevated urinary MMA concentration and %MMA in the early trimester were associated with an increased risk of microcytic anemias in the late trimester. CONCLUSIONS: Our study demonstrated a significant inverse relationship between gestational arsenic exposure and Hb and MCH. Notably, higher MMA and lower methylation capacity to metabolize inorganic arsenic (iAs) in early pregnancy might increase the likelihood of microcytic anemia among pregnant women in late pregnancy.

Prevalence of type 2 diabetes mellitus in relation to arsenic exposure and metabolism in Mexican women.

BACKGROUND: Experimental studies have shown the diabetogenic potential of inorganic arsenic (iAs); however, the epidemiological evidence is still inconclusive. This could be explained by differences in exposure, metabolism efficiency, nutritional and genetic factors. OBJECTIVE: To evaluate the association between type 2 diabetes mellitus (T2DM) prevalence with arsenic exposure and metabolism, considering one-carbon metabolism nutrient intake and arsenite methyltransferase (AS3MT) polymorphisms. METHODS: From healthy controls of a case control study for female breast cancer in northern Mexico, 227 self-reported diabetic women were age-matched with 454 non-diabetics. Participants were interviewed about dietary, sociodemographic and clinical characteristics. Urinary iAs metabolites were determined by HPLC-ICP-MS, methylation efficiency parameters were calculated, and AS3MT c.860 T > C and c.529-56G > C genotypes were determined. Unconditional logistic regression models were used to evaluate associations. RESULTS: Total arsenic in urine (TAs) ranged from 0.73 to 248.12 µg/L with a median of 10.48 µg/L. In unadjusted analysis, TAs (µg/g) was significantly higher in cases than controls, but not when expressed as TAs (µg/L). Cases had significantly lower urinary monomethylarsonic acid percentage (%MMA), first methylation ratio (FMR), creatinine, and choline and selenium intakes. In multi-adjusted models and in women without HTA history T2DM showed significant positive associations with %iAs and FMR, respectively, and a significant negative association with %DMA. In participants with HTA history there was a marginal positive association (p = 0.08) between T2DM and TAs concentrations (µg/g) without other significant associations. CONCLUSIONS: Our results support an association between T2DM prevalence and iAs metabolism but not with urinary arsenic levels. However, elucidation of the interplay among iAs metabolism, T2DM and HTA merit further studies.

The association of arsenic exposure and arsenic metabolism with all-cause, cardiovascular and cancer mortality in the Strong Heart Study.

The effect of low-moderate levels of arsenic exposure and of arsenic metabolism on mortality remains uncertain. We used data from a prospective cohort study in 3600 men and women aged 45 to 75 years living in Arizona, Oklahoma, and North and South Dakota. The biomarker of inorganic arsenic exposure was the sum of urine inorganic (iAs), monomethylated (MMA) and dimethylated (DMA) arsenic compounds (Æ©As) at baseline. The proportions of urine iAs, MMA and DMA over the Æ©iAs, expressed as iAs%, MMA%, and DMA%, respectively, were used as biomarkers of arsenic metabolism. Arsenic exposure and arsenic metabolism were associated with all-cause, cardiovascular, and cancer mortality. For each interquartile range (IQR) increase in Æ©As (12.5 µg/L, overall range 0.7-194.1 µg/L), the adjusted hazard ratios (aHRs) were 1.28 (95% CI 1.16-1.41) for all-cause mortality, 1.28 (1.08-1.52) for cardiovascular mortality and 1.15 (0.92-1.44) for cancer mortality. The aHR for mortality for each IQR increase in MMA%, when iAs% is decreasing, was 1.52 (95% CI 1.16-1.99) for cardiovascular disease, 0.73 (0.55-0.98) for cancer, and 1.03 (0.90-1.19) for all-cause mortality. These findings at low-moderate levels of arsenic exposure highlight the need to implement public health measures to protect populations from involuntary arsenic exposure and for research to advance the biological and clinical understanding of arsenic-related health effects in general populations.

Adaptation mechanisms of arsenic metabolism genes and their host microorganisms in soils with different arsenic contamination levels around abandoned gold tailings.

Soil around the gold tailing due to the smelting process of wastewater and solid waste can lead to metal (loids) contamination, especially arsenic (As). Soil microorganisms have gradually evolved adaptive mechanisms in the process of long-term adaptation to As contamination. However, comprehensive investigations on As metabolism genes and their host microbial communities in soil profiles with different levels under long-term As contamination are lacking. There are selected three typical soil profiles (0-100 cm) with different metal (loids) contamination levels (L-low, M-moderate and H-high) around tailings in this research. It uses a Metagenomic approach to explore the adaptation mechanisms of arsenic metabolism genes and arsenic metabolism gene host microorganisms in both horizontal and vertical dimensions. The results showed that four categories of As metabolism genes were prevalent in soil profiles at different As contamination, with As reduction genes being the most abundant, followed by As oxidation genes, then respiration genes and methylation genes. The As metabolism genes arsBCR, aioE, arsPH, arrAB increased with the increase of metal (loid) contaminants concentration. Longitudinal arsA, arrA, aioA, arsM and acr3 increased in abundance in deep soil. Actinobacteria, Proteobacteria, Acidobacteria, and Chloroflexi were the dominant phylum of As metabolism gene host microorganisms. Different concentrations of metal (loid) contamination significantly affected the distribution of host As metabolism genes. Random forest prediction identified As as the most critical driver of As metabolism genes and their host microorganisms. Overall, this study provides a reference for a comprehensive investigation of the detoxification mechanisms of As metabolism microorganisms in soil profiles with different As contamination conditions, and is important for the development of As metabolism gene host microbial strains and engineering applications of microbial technologies to manage As contamination.

Reducing arsenic toxicity using the interfacial oxygen nanobubble technology for sediment remediation.

The arsenic (As)-bearing eutrophic waters may suffer from the dual conditions of harmful algal blooms and release of As, driven by algal-induced hypoxia/anoxia. Here, we investigate the use of interfacial oxygen (O2) nanobubble technology to combat the hypoxia and control As exposure in simulated mesocosm experiments. It was observed that remediation of algal-induced hypoxia at the sediment-water interfaces (SWI) by application of O2 nanobubbles reduced the level of dissolved As from 23.2 µg L-1 to <10 µg L-1 and stimulated the conversion of As(III) to the less toxic As(V) (65-75%) and methylated As (10-15%) species. More than half of the oxidation and all the methylation of As(III) resulted from the manipulation by O2 nanobubbles of microbes responsible for As(III) oxidation and methylation. Hydroxyl radicals were generated during the oxidation of reductive substances at the SWI in darkness, and should be dominant contributors to As(III) abiotic oxidation. X-ray absorption near-edge structure (XANES) spectroscopic analysis demonstrated that surface sediments changed from being sources to acting as sinks of As, due to the formation of Fe-(hydr)oxide. Overall, this study suggests that interfacial O2 nanobubble technology could be a potential method for remediation of sediment As pollution through the manipulation of O2-related microbial and geochemical reactions.

Associations between rice consumption, arsenic metabolism, and insulin resistance in adults without diabetes.

Rice consumption is an important source of arsenic exposure. Little has known about the impact of rice consumption on arsenic metabolism, which is related to insulin resistance. In this study, we examined the associations between rice consumption and arsenic metabolism, and between arsenic metabolism and insulin resistance in non-diabetic U.S adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2003-2016. Rice consumer was defined as ≥0.25 cups of cooked rice/day. HOMA2-IR was calculated using HOMA2 Calculator software based on participant's fasting glucose and insulin values. Urinary arsenic concentrations below limits of detection were imputed first, and then arsenic metabolism (the proportions of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) to their sum) were calculated (expressed as iAs%, MMA%, and DMA%). Using the leave-one-out approach, rice consumers compared with non-consumers had a 1.71% (95% CI: 1.12%, 2.29%) higher DMA% and lower MMA% when iAs% fixed; a 1.55% (95% CI: 0.45%, 2.66%) higher DMA% and lower iAs% when MMA% fixed; and a 1.62% (95% CI: 0.95%, 2.28%) higher iAs% and lower MMA% when DMA% fixed, in multivariable adjustment models. With every 10% decrease in MMA%, the geometric mean ratio of HOMA2-IR was 1.06 (95% CI: 1.03,1.08) and 1.05 (95% CI: 1.02, 1.09) when DMA% and iAs% was fixed, respectively; however, the associations were attenuated after adjusting for body mass index. In stratified analysis, we found that lower MMA% was associated with higher HOMA2-IR in participants with obesity: a 10% increase in iAs% with a 10% decrease in MMA% was associated with higher HOMA2-IR with the geometric mean ratio of 1.05 (95% CI: 1.01, 1.09). Our findings suggest that rice consumption may contribute to lower MMA% that was further associated with higher insulin resistance, especially in individuals with obesity. Future prospective studies are needed to confirm our results in different populations.

High Arsenic Levels Increase Activity Rather than Diversity or Abundance of Arsenic Metabolism Genes in Paddy Soils.

Arsenic (As) metabolism genes are generally present in soils, but their diversity, relative abundance, and transcriptional activity in response to different As concentrations remain unclear, limiting our understanding of the microbial activities that control the fate of an important environmental pollutant. To address this issue, we applied metagenomics and metatranscriptomics to paddy soils showing a gradient of As concentrations to investigate As resistance genes (ars) including arsR, acr3, arsB, arsC, arsM, arsI, arsP, and arsH as well as energy-generating As respiratory oxidation (aioA) and reduction (arrA) genes. Somewhat unexpectedly, the relative DNA abundances and diversities of ars, aioA, and arrA genes were not significantly different between low and high (∼10 versus ∼100 mg kg-1) As soils. Compared to available metagenomes from other soils, geographic distance rather than As levels drove the different compositions of microbial communities. Arsenic significantly increased ars gene abundance only when its concentration was higher than 410 mg kg-1. In contrast, metatranscriptomics revealed that relative to low-As soils, high-As soils showed a significant increase in transcription of ars and aioA genes, which are induced by arsenite, the dominant As species in paddy soils, but not arrA genes, which are induced by arsenate. These patterns appeared to be community wide as opposed to taxon specific. Collectively, our findings advance understanding of how microbes respond to high As levels and the diversity of As metabolism genes in paddy soils and indicated that future studies of As metabolism in soil or other environments should include the function (transcriptome) level. IMPORTANCE Arsenic (As) is a toxic metalloid pervasively present in the environment. Microorganisms have evolved the capacity to metabolize As, and As metabolism genes are ubiquitously present in the environment even in the absence of high concentrations of As. However, these previous studies were carried out at the DNA level; thus, the activity of the As metabolism genes detected remains essentially speculative. Here, we show that the high As levels in paddy soils increased the transcriptional activity rather than the relative DNA abundance and diversity of As metabolism genes. These findings advance our understanding of how microbes respond to and cope with high As levels and have implications for better monitoring and managing an important toxic metalloid in agricultural soils and possibly other ecosystems.

Arsenic exposure and metabolism in relation to blood pressure changes in pregnant women.

Arsenic is concerned with cardiovascular diseases including hypertension, atherosclerosis, and endothelial dysfunction. However, what effects the arsenic exposure and the arsenic metabolism have on hypertensive disorders of pregnancy (HDP) and blood pressure changes during pregnancy remain largely unknown. Our goal was to assess the associations of arsenic exposure and arsenic metabolism with HDP and blood pressure changes in pregnant women through a prospective birth cohort study. A total of 1038 women who were pregnant (52 HDP, 986 non-HDP participants) were included. Arsenic species of spot urine samples collected at three trimesters were measured, which included inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA). Arsenic metabolism was evaluated as the percentages of iAs, MMA, and DMA respectively (i.e., iAs%, MMA%, and DMA%). Outcomes were HDP and systolic, diastolic, and mean arterial pressure changes during pregnancy. We employed mixed linear models to investigate the relationships between arsenic exposure and arsenic metabolism with changes in blood pressure during pregnancy. Poisson regression with a robust error variance with generalized estimating equations (GEE) estimation was used so that the associations of arsenic exposure and arsenic metabolism with HDP could be estimated. In this study, there was a significant relationship between the concentrations of urinary DMA and the weekly change in systolic blood pressure (SBP) (ß = -0.10; 95% CI: -0.15, -0.05), diastolic blood pressure (DBP) (ß = -0.07; 95% CI: -0.11, -0.02) and mean arterial pressure (MAP) (ß = -0.08; 95% CI: -0.12, -0.04). Higher DMA% was accompanied with lesser weekly increase in SBP (ß = -0.05; 95% CI: -0.10, 0.00), DBP (ß = -0.06; 95% CI: -0.10, -0.01) and MAP (ß = -0.06; 95% CI: -0.09, -0.01) during pregnancy. There was a positive association with the highest tertile of iAs% and weekly change of SBP (ß = 0.08; 95% CI: 0.03, 0.13), DBP (ß = 0.07; 95% CI: 0.03, 0.11) and MAP (ß = 0.07; 95% CI: 0.03, 0.11). No association was found between each arsenic specie and arsenic metabolism marker in the first trimester and risk of HDP. Arsenic exposure and arsenic metabolism during pregnancy potentially change blood pressure of pregnant women. These findings may be significance as even modest elevation of blood pressure can increase the risk of cardiovascular disease.