Mechanism Of Intestinal Mucosal Barrier Regulated Intestinal Injury Induced By PM2.5

The intestinal barrier is an essential target for PM2.5,which is responsible for causing intestinal damage.The intestinal microbiome plays a critical role in regulating the intestinal barrier function.Thus,intestinal microbiota might play an important role in intestinal injury caused by PM2.5.However,the study on PM2.5 induced intestinal damage has barely focused on the gut microbiota,not mention to mechanisms.In the study,gastric administration was used to chronically expose to high and low concentrations of PM2.5 to normal and DSS-treated mice,respectively,and to study the effects of PM2.5 on normal and colitis mice.The main results are as follows:1.After fed with PM2.5 for 35 days,we found the impact of PM2.5 on the normal group:(1)Through colonic tissue sections of mice and H&E staining,we observed a certain degree of intestinal damage in mice fed with high and low concentrations of PM2.5(2)Using Unweighted PCo A analysis of samples based on Bray-Curtis distance matrix,we found that in the normal group of mice,the fecal flora structure of the mice exposed to high and low concentrations of PM2.5 was significantly different from the control group(ANOSIM R: 0.4487,P = 0.001).The content of Bacteroides increased considerably,the level of Firmicutes decreased considerably.It shows that PM2.5 changed the mouse intestinal flora.(3)Through the detection of inflammation-related factors by RT-PCR,it was found that the colonic tissues of mice in the highconcentration PM2.5-fed group had significantly more inflammatory reactions compared with the control group.(4)Detection of colon tight junction protein-related factors by RT-PCR revealed that the colon tissue of mice in the high-concentration PM2.5 fed group had decreased tight junction at m RNA level,and increasing colonic permeability compared with the control group.The increase caused the bacteria to translocation into the colon and liver tissues.It was found that the bacterial product LPS content increased in liver tissues of mice,which further explained that the mice intestinal barrier was damaged.(5)Detection of colon toll-like receptor-related factors by RT-PCR revealed that TLR-2 and TLR-4 were significantly increased(P<0.05),and TLR-9 was significantly decreased(P <0.05)in high-concentration PM2.5-fed mice.It is suggested that PM2.5 may affect the intestinal barrier through TOLL-like receptors.(6)PM2.5 also has a specific effect on the immune system of mice,specifically by reducing the levels of SOD,LZM,and C3 and C4 complement in the spleen,and exacerbating the inflammatory response in the liver of mice.2.Effects of PM2.5 on DSS-treated mice: After fed with PM2.5 for 35 days,it was found that(1)Through mice colon tissue sections and H&E staining,we observed in high and low concentration PM2.5 feeding groups,the mice suffered from intestinal damage compared with the control group.(2)Using unweighted PCo A analysis of samples based on Bray-Curtis distance matrix,we found that the microbiota structure of the mice in the high-concentration and low-concentration PM2.5 exposure groups were significantly different from the control group(ANOSIM R: 0.2394,P = 0.001).The total bacterial load in feces of mice increased dramatically,which indicated that PM2.5 changed the intestinal flora of mice.(3)Through RT-PCR detection of inflammation-related factors(IL1-?,TNF-?),it was found that the colonic tissues of mice in the high-concentration PM2.5 feeding group had an increased inflammation compared with the control group.(4)Detection of colon tight junction proteinassociated factors(ZO-1 and claudin-1)by RT-PCR revealed that the colon tissue of mice fed with low and high concentrations of PM2.5 fed group had a decrease in tight junction protein compared with the control group(ANOVA,all P <0.05),the colonic permeability increased.The increased colonic permeability led to the translocation of bacteria to the colon and liver tissues.It found that the bacterial product LPS content increased in the liver tissues of mice fed with a high concentration of PM2.5,which further shows that PM2.5 aggravated intestinal barrier damage in the colitis mice.(5)PM2.5 also has a specific impact on the immune system of the colitis mice,specifically by reducing the levels of SOD and complement C3 and C4 in the spleen of mice,increasing the level of LZM in the spleen,and exacerbated the inflammatory response in the liver of mice.In summary: PM2.5 exposure leads to intestinal damage in mice and a significant inflammation in the colon.Further examination revealed that the structure of the intestinal flora of the mouse has changed significantly,and the expression of tight junction protein in the mouse colon is significantly down,And an increase in bacteria and LPS was detected in the liver of mice,which together indicate the damage to the intestinal barrier in mice.A damaged intestinal barrier may cause PM2.5 to affect the liver through the "gut-liver" axis,causing an inflammatory response in the liver.