Gut Microbiome Perturbations Induced by Bacterial Infection Affect Arsenic Biotransformation

Lü, Kun; Cable, Peter H.; Abo, Ryan; Ru, Hongyu; Graffam, Michelle E.; Schlieper, Katherine Ann; Parry, N.; Levine, Stuart S.; Bodnar, Wanda M.; Wishnok, John S.; Stýblo, Miroslav; Swenberg, James A.; Fox, James G.; Tannenbaum, Steven R.

doi:10.1021/tx4002868

Cited by 77 publications

(56 citation statements)

References 67 publications

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“…Bioaccessiblity and bioavailability play a role in potential health effects from arsenic exposure. Most of the metabolism of arsenic is thought to take place in the liver, however, there is evidence that gut microbiome metabolism may also take place and could have a significant impact on absorption/excretion and associated health effects form arsenic exposure (60,86). Unmeasured bioaccessibility/bioavailability will increase the variation in our arsenic exposure estimates and when using the metabolite variables as outcomes we would have reduced power to detect associations with these exposure factors.…”

Section: Discussionmentioning

confidence: 99%

Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity

Jansen

Argos

Lin

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Exposure to inorganic arsenic (iAs), class I carcinogen, affects several hundred-million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%), varies across individuals, reflecting differences in arsenic metabolism capacity. Methods The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal components (PC) analysis of arsenic species. Results Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (2nd methylation step), and PC2 appears to represent capacity to convert iAs to MMA (1st methylation step). PC 1 was positively associated (p <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negative associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations. Conclusions Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions. Impact: This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles.

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Section: Discussionmentioning

confidence: 99%

Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity

Jansen

Argos

Lin

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…10 Studies have clearly illustrated that gut microbiota significantly affect As metabolism by, for example, reduction, methylation, and thiolation. 11 As metabolism in contaminated soil by human gut microbiota can affect As bioaccessibility and speciation. 10,12 Therefore, As biotransformation must be considered an essential part of the risk assessment of oral soil As exposure using in vitro methods.…”

Section: ■ Introductionmentioning

confidence: 99%

In Vitro Method To Assess Soil Arsenic Metabolism by Human Gut Microbiota: Arsenic Speciation and Distribution

Yin

Zhang

Cai

et al. 2015

Environ. Sci. Technol.

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Arsenic (As) speciation and distribution are two important factors in assessing human health risk from As-contaminated soil. In this study, we used the combination of physiologically based extraction test (PBET) and Simulator of Human Intestinal Microbial Ecosystem (SHIME) to determine soil As metabolism by human gut microbiota. The results showed that the percentage of soil arsenate [As(V)] transformation reached 22.1−38.2%, while that of arsenite [As(III)] attained 66.5−92.0%; 30.1−56.4% of As(V) transformed was attached to the soil solid phase. In comparison to sequential extraction results, almost all amorphous Fe/Al-oxide-bound As was liberated in the colon phase. An X-ray absorption nearedge structure (XANES) showed that the As(III) percentage in the soil solid phase reached 16.6−26.9% and reached 73.4% (soil 1) in the colon phase. Additionally, plenty of As(III) and different extents of methylation were also observed in colon extraction solution. As bioaccessibility in the colon phase was 1.8−2.8 times that in the small intestinal phase. Our results indicated that human gut microbiota increased As bioaccessibility, and large amounts of As(III) were adsorbed onto the soil solid phase as a result of microbial reduction. Determining As speciation and distribution in extraction solution and soil solid phases will allow for an accurate assessment of the risk to human health upon soil As exposure. ■ INTRODUCTIONArsenic (As) is a common toxic contaminant that is extensively distributed in the environment. 1 Human exposure to As in soils is a major public concern and is associated with serious risks to human health because As species are known carcinogens. 2,3 In most cases, human exposure to soil As occurs via inhalation, inadvertent oral ingestion, and dermal contact. 4,5 Inadvertent oral ingestion has been considered an important exposure route for soil As, especially ingestion through outdoor hand-to-mouth activities by children. 6 The estimation of As bioaccessibility (gastric and small intestinal phases) in contaminated soils through in vitro methods has been used for human health risk assessment. On the basis of previous studies, 7−9 simple, fast, and inexpensive in vitro methods can effectively estimate in vivo relative As bioavailability. Generally, bioaccessibility is defined as the fraction of As that is soluble in the gastrointestinal environment of humans and available for absorption, whereas bioavailability is determined by the fraction of As that is absorbed into the systemic circulation. 7,8 Currently, As bioaccessibility in the gastric and small intestinal phases may underestimate its harm to human health. 10 Studies have clearly illustrated that gut microbiota significantly affect As metabolism by, for example, reduction, methylation, and thiolation. 11 As metabolism in contaminated soil by human gut microbiota can affect As bioaccessibility and speciation. 10,12 Therefore, As biotransformation must be considered an essential part of the risk assessment of oral soil As exposure using i...

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“…As ( (Lu et al, 2013). The previous study showed that As(V) is the predominant form (nearly N99%) for the small intestinal digest in contaminated soils (Yin et al, 2015b).…”

Section: Tablementioning

confidence: 96%

Variability of arsenic bioaccessibility and metabolism in soils by human gut microbiota using different in vitro methods combined with SHIME

Yin

Zhang

et al. 2016

Science of The Total Environment

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• Five in vitro gastrointestinal methods combined with SHIME (colon phase) were used.• As bioaccessibility varied in the colon phase among these methods.• Plenty of As(III) and methylated arsenicals by microbial transformation were observed.• As bioaccessibility in PBET/SBRC-SHIME colon phase were closer to in vivo results for NIST 2710a. Arsenic (As) speciation analysis is essential when evaluating the risks upon oral exposure to As-contaminated soils. In this study, we first investigated the variability in the As bioaccessibility and speciation using a combination of five common in vitro methods (SBRC, PBET, DIN, UBM and IVG) (gastric and small intestinal phases) and the SHIME model (colon phase). Our results indicate that the As bioaccessibility varies in the colon phase. An increase in the As bioaccessibility for SBRC and PBET, and a decrease for UBM and IVG were observed in the colon phase. In addition, we found different extents of methylation and large amounts of arsenite [As(III)] due to microbial reduction in the colon digests. The UBM-SHIME method displayed a higher methylation percentage of 13.5-82.1%, but a lower methylation percentage of 0.2-21.8% was observed in the SBRC-SHIME method. Besides, The MMA V levels in the colon digests were positively correlated with those of As(III) and DMA V , so DMA V can be considered an indicator to evaluate the As metabolic speed of in vitro cultured human gut microbiota. Based on the standard reference soil of NIST 2710a, the As bioaccessibility in the colon phase of PBET-SHIME and SBRC-SHIME were the closest to the in vivo results. Combining in vitro methods and SHIME will remarkably affect the accurate assessment of potential risks to human health associated with oral exposure to soil As.

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Gut Microbiome Perturbations Induced by Bacterial Infection Affect Arsenic Biotransformation

Cited by 77 publications

References 67 publications

Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity

Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity

In Vitro Method To Assess Soil Arsenic Metabolism by Human Gut Microbiota: Arsenic Speciation and Distribution

Variability of arsenic bioaccessibility and metabolism in soils by human gut microbiota using different in vitro methods combined with SHIME

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