Study Of Salinity And Gut Microbes On The Metabolism Of Arsenic In Organisms And Its Risk

Arsenic(As)is a class of highly toxic substances that transferred along the food chain and accumulated in organisms,and it is of great importance to control health risk of As.Arsenate[As(Ⅴ)] can be reduced to the more toxic arsenite [As(Ⅲ)] in living organisms,and methylated to less toxic organic As,including monomethylarsonic(MMA),dimethylarsenic(DMA),and arsenobetaine(AsB).Marine fish,one of the important food sources containing As,and its As concentration is higher than that of freshwater fish.Salinity may be an important factor affecting As bioaccumulation.The intestine is a main site of As bioaccumulation and metabolism,and intestinal microorganisms can affect the bioaccumulation and metabolism of As.Investigating the regulatory effects of salinity and intestinal microorganisms on inorganic As can provide a more comprehensive and systematic assessment for the health risk of As.Therefore,the objectives of this paper are:(1)to clarify the differences of bioaccumulation and biotransformation of inorganic As in marine fishes driven by salinity and its regulatory mechanism;(2)to establish a mouse model of intestinal microbial disturbance to study the differences of bioaccumulation and biotransformation of As(Ⅴ)and AsB in mice under intestinal microbial disturbance,and to reveal the role of specific microorganisms in the process of As bioaccumulation and biotransformation.Aiming at the above research objectives,the research is carried out as follows:(1)In order to explore the effects of salinity on the biological biotransformation of inorganic As in marine fish and its regulation,Oryzias melastigma was fed with food As after different salinity acclimation.The As concentrations in differnet tissues,including head,gill,liver,intestine,and muscle,were analyzed to investigate the bioaccumulation and biotransformation in fish.And the differential metabolites and differentially expressed genes in muscle were analyzed to by transcriptomics and metabolomics in fish.The results showed that O.melastigma effectively absorbed As from diet and had high bioaccumulation in the muscle and head.The concentration and proportion of total As and AsB in the muscle and head were positively correlated with salinity.cdo1,dmgdh,gclm,gpx3,mat2 ab,psat1 affected the bioaccumulation and biotransformation of inorganic As by changing glutathione metabolism,serine metabolism,betaine metabolism,and methionine cycle.Glutathione metabolism provided electrons to reduce As(Ⅴ)to As(Ⅲ),and the serine,betaine,methionine cycle promoted the methylation of As.Importantly,in the As treatments,the concentration of AsB was the highest at the salinity of 30‰,while the concentration of choline and betaine was the lowest at the salinity of 30‰,showing an opposite trend.Therefore,AsB may replace part of betaine and accumulate in fish as osmotic pressure regulator.This study revealed the regulatory mechanism of salinity on biological biotransformation of inorganic As,and the results of this study provided theoretical basis and data support for promoting health risk assessment and prevention and control of As.(2)In order to clarify the effects of intestinal microbes on As exposure in mice,Cefoperazone(Cef)was used to construct an intestinal microbial disturbance mouse model.Total As and As morphology were determined from the heart,liver,spleen,lung,kidney,stomach,intestine,muscle,brain and stool of mice,and the intestinal microbiota was deteted through 16 S rRNA sequencing technology.The results showed that Cef significantly damaged the intestinal microbial composition of mice.The disturbance of intestinal microorganisms increased the bioaccumulation of As(Ⅴ)and AsB,reduced the excretion of As(Ⅴ)and AsB in feces,and has an important influence on the biotransformation of As(Ⅴ).Cef significantly decreased Blautia and Lactobacillus,and increased Enterococcus,resulting in the enhancement of As bioaccumulation and methylation in mice.This study found that Lachnoclostridium,Erysipelatoclostridium,Blautia,Lactobacillus and Enterococcus are biomarkers involved in As metabolism.Thus,specific intestinal microbes can significantly influence the bioaccumulation and biotransformation of As in mice,thus affecting the health risk assessment.This study provides a basis for comprehensive assessment of health risks in As exposed populations.In conclusion,salinity can affect the metabolism of glutathione,serine,betaine and methionine,and then regulate the bioaccumulation and biotransformation of inorganic As in marine fish.Intestinal microbiome disturbance mice have decreased Blautia and Lactobacillus and increased Enterococcus,resulting in increased bioaccumulation of As in the body and enhanced methylation.Therefore,the regulatory effects of salinity and intestinal microbes on inorganic As can help us to evaluate As health risks in a more comprehensive and systematic way,efficiently propose As risk prevention and control strategies,and provide solutions for avoiding the ecological health risks of As.