Pathogenesis Of Selenium-deficient Diarrhea Caused By Intestinal Flora

Selenium is a micronutrient that plays an important role in various physiological processes of humans and animals.Chronic selenium deficiency can lead to a variety of metabolic diseases.Studies have found that chronic selenium deficiency can cause chronic diarrhea.Intestinal flora,known as the second gene,can affect a variety of biological processes in the body by regulating microbial homeostasis in the intestine,thus affecting the health of the body.Changes in a variety of external factors can cause changes in the intestinal flora,and such changes are not consistent when the same variables are treated.However,the current research on the factors that regulate the distribution of intestinal flora,especially the influence of chronic selenium deficiency,is not thorough enough.Therefore,this study established a chronic selenium-deficient mouse model and administered probiotics to selenium-deficient mice to test the regulation effect of improving the species composition structure of intestinal flora on intestinal damage.Through metagenomic sequencing analysis of mouse intestinal contents,combined with downstream molecular biology techniques to verify and analyze the mechanism of chronic selenium deficiency on intestinal damage in mice and the regulation of intestinal flora species composition.The specific results are as follows:To explore the damage of the intestinal tract caused by selenium deficiency in mice,this study analyzed and verified it by a variety of molecular biological techniques.Histological analysis showed that in test 1,compared with the normal group,the small intestine tissues of mice in the Se deficient group had obvious pathological changes,including shorter and broken intestinal villi,fewer cup cells,fewer intestinal crypts,and thinner muscular layer.After ingestion of Lactobacillus_reuteri,histopathological changes occurred in the LSe J group.Although the intestinal villi in the LSe J group became shorter or even broken,compared with the LSe N group,the number of intestinal crypts became more,the muscular layer became thicker,and the intestinal villi arrangement was denser.We examined m RNA expression levels of small intestine genes related to inflammation,autophagy,endoplasmic reticulum stress,apoptosis,tight junction,and smooth muscle contraction.It was found that m RNA levels of NF-κB,IκBα,p38,IL-1β,and TNF-α were significantly increased in LSe group and LSe N group,while m RNA levels of IL-10 were significantly decreased.This demonstrated inflammation in the small intestine of the selenium-deficient mice.The m RNA levels of Beclin,ATG7,ATG5,and LC3α in the small intestine of LSe group and LSe N group were significantly increased,while the m RNA levels of p62 were slightly decreased,compared with the control group.This suggests that autophagy occurs in the small intestine of selenium-deficient mice.Compared with the control group,m RNA levels of Ba K,Pum,Caspase-3,RIP1,and RIPK3 were significantly increased in the LSe and LSe N groups,while m RNA levels of Bc L-2 and Bc L-w were significantly decreased.This indicated that the small intestine cells of selenium-deficient mice underwent apoptosis.m RNA levels of PERK,IRE1,el F2α,GRP78,and CHOP were significantly increased compared with the control group.This showed that the small intestine cells of selenium-deficient mice had ERS.The m RNA levels of tight junction proteins ZO-1,ZO-2,Occludin,and E-cadherin increased significantly.This showed that the tight connections in the small intestine were broken in selenium-deficient mice.Expressions of smooth muscle contract-related genes such as Ca M,MLC,MLCK,Rho,and Rho A were increased in LSe and LSe N groups.This indicates abnormal contraction of small intestinal smooth muscle in selenium deficiency.These results were mitigated in the LSe J group.To explore the specific effects of selenium deficiency on the intestinal flora,the results were obtained by metagenomic analysis of the contents of the small intestine in mice.In trial 1,the bacteria with the highest abundance in the normal group were Dubosiella(25.4976%),Lactobacillus(12.2355%),and Romboutsia(18.7987%)Faecalibaculum(11.1052%),respectively.The highest abundance bacteria in the low selenium group were Dubosiella(22.8274%),Lactobacillus(18.7323%),Bifidobacterium(20.2125%),and Ileibacterium(11.0841%).Lactobacillus_reuteri,a probiotic,was selected for subsequent regression tests by screening several bacteria with large abundance changes in test I.By administering Lactobacillus reuteri solution to selenium-deficient mice,the species composition of microflora in selenium-deficient mice was changed.The highest abundance strain in the normal group was Lactobacillus(25.5853%),Dubosiella(11.1173%),Limosilactobacillus(7.6615%),and Faecalibaculum(6.4587%).The highest abundance strain in LSe N group was Lactobacillus(22.6493%),Dubosiella(15.6075%),Faecalibaculum(11.4175%),and Limosilactobacillus(10.5902%).The highest abundance bacteria in LSe J group were Lactobacillus(32.6652%),Ileibacterium(15.0231%),Faecalibaculum(13.0478%),Limosilactobacillus(9.1544%).In conclusion,changes in the relative abundance of intestinal flora among different species may be related to inflammation of intestinal tissue cells,autophagy,endoplasmic reticulum stress,apoptosis,tight junction,and abnormal smooth muscle contraction.After treatment with probiotics,intestinal tissue cell inflammation,autophagy,endoplasmic reticulum stress,apoptosis,tight junction,and smooth muscle contraction abnormalities were improved.Intestinal flora plays an important role in the mechanism of chronic diarrhea caused by selenium deficiency.