Alleviation Effects On The Toxicity Of PFOA By Lactic Acid Bacteria And Their Mechanism

Pentadecafluorooctanoic acid(PFOA)is a new type of organic compound which has been commonly used due to its fine hydrophobic and oleophobic properties.PFOA can be absorbed by the body through diet,drinking water and skin contact.PFOA has hepatotoxicity,reproductive toxicity,developmental toxicity,neurotoxicity and potential carcinogenicity.At present,the mitigation of PFOA toxicity is mainly through the intake of natural extracts with high antioxidant activity.However,in order to produce enough protective effect,a large amount of natural extracts intake is necessary which may has potential hazard.In previous studies,it has been confirmed that lactic acid bacteria can alleviate liver damage and immune damage in mice caused by PFOA through antioxidant function or absorption capacity.But it remains unknown which capacity plays the main role in the process of toxicity alleviation.Moreover,as the first organ in the body exposed to PFOA,intestinal tract is continuously exposed in intestinal and hepatic circulation.However,the influence of PFOA on gut and gut microbiota has rarely been studied.This study explored the effects of PFOA on the intestinal tract and its microenvironment,and the mitigation effect and possible mechanism of lactic acid bacteria on the toxicity of PFOA by engaging lactic acid bacteria with different absorption effects on PFOA combining with the different antioxidant capacities.In order to study the hepatic and immunological injury caused by PFOA exposure on mice and the effect of PFOA on mice intestinal microenvironment including fecel short-chain fatty acids and gut microbiota,we established a subacute PFOA exposure model and a subchronic PFOA exposure model.The content of propionic acid and n-butyric acid in the subacute highdose PFOA exposure mice decreased significantly(P<0.05).The contents of isobutyric acid,nbutyric acid and n-valeric acid in the feces of subchronically exposed mice decreased significantly(P<0.05).Gut microbiota analysis showed that there was no significant changes in intestinal flora diversity in the subacute exposure model compared to the control group.But in the high dose group,the relative abundance of Staphylococcus,Lactobacillus and Bacillus were significantly increased(P <0.01),and the relative abundance of Desulfovibrio was significantly decreased(P<0.05).In the subchronic exposure model,compared with the control group,the relative abundance of Bacteroides in the medium and high dose exposure groups was significantly lower(P<0.01)and Oscillospira increased significantly(P<0.05).These indicated that PFOA exposure may lead to gut microbiota dysbiosis,which may further induce microbial infection in subacute exposure groups.In addition,subchronically exposed gut microbiota analysis may explain the weight loss of mice caused by PFOA exposure and abnormal bile metabolism.Subsequently,lactic acid bacteria with mitigating potential for PFOA toxicity were screened from two aspects: the absorption and antioxidative capacity of PFOA in vitro.22 strains of lactic acid bacteria isolated from human feces or kimchi vegetables was investigated,with the commercial strain Lactobacillus rhamnosus GG(LGG)as a control strain.Combined with the determination of the antioxidant capacity of lactic acid bacteria,L.fermentum 8-9 and LGG(high absorption and high antioxidant capacity),L.plantarum 170-0-1and L.plantarum F-FJND-D6-M8(low antioxidant and high antioxidant capacity),L.casei NT15-7 and L.brevis CQ-BS-1-3(low antioxidant capacity and high absorption capacity),L.fermentum FJSNTR9-8 and L.fermentum 6-3(low anti-oxidation ability and low absorption capacity)were selected for further investigation.In order to verify the mitigating effect of lactic acid bacteria on PFOA toxicity in vivo,mice were exposed to PFOA together with the intervention of lactic acid bacteria.Data of inflammatory factors,biochemical indicators and oxidative stress indicators in the liver and histopathological section analysis showed that L.brevis CQ-BS-1-3 can effectively alleviate the hepatotoxicity and immunotoxicity by PFOA.It is speculated that the absorption capacity of lactic acid bacteria to PFOA plays a major role in alleviating various damages(liver and immune system)caused by PFOA exposure.Besides,the antioxidant capacity of lactic acid bacteria can alleviate liver damage caused by PFOA to some extent.In addition,the content of acetic acid,butyric acid in the intestine of mice decreased because of PFOA exposure,while L.fermentum 6-3 recoverd the acetic acid and butyric acid content to a certain extent after intervention,the correlation between L.fermenti 6-3 intervention and the changes of lactic acid bacteria and PFOA toxicity suggests that the effect of lactic acid bacteria on short-chain fatty acids in the intestine may be the one of the mechanisms of lactic acid bacteria to alleviate PFOA toxicity.Furthermore,the results of metagenomic analysis showed that PFOA did not cause significant changes in the composition of the gut microbiota,but caused a change in the relative abundance of some flora.For example,the relative abundances of the genus Paraprevotellaceae and S24-7,Lactobacillus and Allobaculum were increased to some extent compared with the control group,while the relative abundance of Eubacteriaceae,Clostridiaceae,Blautia,Adlercreutzia,Holdemania,Coprobacillus and Bacteroides were decreased compared to the control group.Intervention of some strains of the lactic acid bacteria recovered the gut microbiota dysbiosis in mice.Combining the relationship between strains and liver diseases,it is speculated that PFOA exposure may further aggravate liver injury by inducing intestinal flora disorder,and lactic acid bacteria intervention can alleviate the toxic effect of PFOA by regulating intestinal damage.