Arsenic Metabolism And Toxicity Influenced By Ferric Iron In Simulated Gastrointestinal Tract

Arsenic(As)is a widely distributed metalloid on earth,it can cause various kinds of cancers and non-cancer disease.Drinking water is one of the main sources exposing to As for human.Metabolism of As in the human can changes As species,and different As species have different toxicity.Many compounds and elements ean also affect As toxicity.Among these factors,iron(Fe)is a common trace element in drinking water However,little is known about how environmental concentrations of Fe affect the metabolism and toxicity of As in drinking water.In the study,As metabolism and toxicity were investigated by using the in vitro stimulated gastrointestinal tract.An dynamic model system(Simulator of the Human Intestinal Microbial Ecosystem,SHIME)was used to simulate the human gut.High performance liquid chromatography and inductively coupled plasma mass spectrometry was applied to analyze As species including inorganic As?(iAs?),inorganic As?(iAs?),monomethylated arsenic(MMA)and dimethylarsine(DMA).The atomic absorption spectrometry was applied to analyze Fe concentration.High-throughput sequencing(Illumina Miseq)was conducted to analyze the microbial community.Cytotoxicity experiments in HepG2 and Caco2 were applied to evaluate toxicity of bioaccessible As.The Transwell was used to simulate the absorption.The main results were as follows:1.In As alone group,the bioaccessible fraction of As was continuously decreased from stomach to colon.Compared with soluble As in the stomach,soluble As concentration in small intestine had a sharply decrease,the percentage of bioaccessible As separately decreased 61% and 59% in 100 ?g/L and 600 ?g/L As group.When the Fe and As were co-exposed,it had a similar change in soluble As from stomach to colon,but 0.3 mg/L Fe and 3 mg/L Fe significantly reduced the soluble As to 15% and 14% in small intestine while it was 37% in As alone group.In As alone exposure groups,ascending colon indicated the occurrence of As methylation.When As and Fe were co-exposed,0.1 mg/L and 0.3 mg/L Fe could significantly increase As methylation in transverse and descending colon,and the 0.3 mg/L Fe induced the highest level of As methylation,which levels of methylation(MMA?DMA)were sperately 42%and 51%in transverse and descending colon.It is interesting that 3 mg/L Fe decreased As methylation in transverse and descending colon.2.The exposure of As and Fe could affect the gut microbial community in the human colon and the gut microbiota played an important role in As metabolism.IAs? was metabolized into four species.Among the four species,iAs? and iAsv indicated a significant effect on the composition of gut microbiota,and 3 mg/L Fe moderated the effects.Clostridium ??a,Bacteroides,Alistipes,Bilophila,Alcaligenes,Cloacibacillus,Bordetella and Kerstersia indicated a high As resistance.Additionally,Bacteroides,Clostridium ??a,Alistipes and Bilophila had As resistance and the potential ability to methylate As.3.For As alone exposure,the effluent from stimulated colon significantly increased the intracellular ROS levels.When Fe was added,compared to As alone exposure,no significant difference on ROS levels was found in ascending and descending colon.0.3 mg/L and 3 mg/L Fe in transverse colon significantly decreased the levels of ROS,additionally,0.3 mg/L and 3 mg/L Fe in transverse and descending colon significantly increased the cell viability and 0.1 mg/L Fe in descending colon significantly increased the cell viability.The cytotoxicity of stimulated solutions of four As species were almost consistent with the results of As methylation,it had a higher toxicity in the low-level methylation group,and lower toxicity in the higher-level methylation group.In the experiment of Transwell,absorbed As was increased with the time along,in the 180 min after exposure,the percentage of absorbed iAs? was higher than the percentage of exposed iAs?,the percentage of abosorbed methylated As was same with the exposed.In conclusion,the present study showed that low-level Fe could change the bioaccessibility,metabolism and toxicity of As in simulated human gastrointestinal tract,and the gut microbiota played an important role in this process.Fe decreased As bioaccessibility by the co-flocculation in small intestine,affected gut microbial community in colon,and thus caused changes in As methylation and toxicity.Our results demonstrated that,when conducting health risk assessment of As in drinking water,the residual Fe should be considered.