Microbiota mitigate Caddy-Induced Lung Injury via Modulating Survivin, Matrix Metalloproteinase-9 and Janus Kinase-2 Gene Expression

Abstract

: Lung injury is one of the most serious consequences post cadmium dichloride (caddy) exposure. Matrix metalloproteinases are calcium and zinc dependent endopeptidases possess the ability of degrading various components of the extracellular matrix. Moreover, MMP-9 is believed to be engaged to lung injury via degradation of the extracellular matrix of blood-air barrier. Furthermore, survivin as an inhibitor of apoptosis plays an important role in lung injury. On the other hand, there are obvious beneficial properties of microbiota due to their ability to bind trace elements in the body improving intestinal microbial balance. The present study highlights the therapeutic beneficial role of probiotic administration against caddy-induced lung injury in mice. : Lung injury was induced via caddy intoxication (20 mg.kg−1) in Swiss albino mice after pretreatment with Acidobacillus or Lactobacillus in a dose of 5 × 1010 colony forming units (CFU) for one week as a protective regimen, then animals received Acidobacillus and Lactobacillus either alone or added to folic acid for concessive 21 days. Molecular analysis of survivin, MMP-9 and JAK-2 gene expression was assessed in addition to, histopathological examination of lung tissue. : A significant elevation in both survivin and MMP-9 was observed upon caddy lung injury. On the other hand, an obvious reduction in Jak-2 gene expression post caddy lung intoxication was recorded. Treatment via microbiota including Acidobacillus and Lactobacillus either alone or added to folic acid declared a significant modulation of all the altered parameters with the superiority of Lactobacillus combined with folic acid group as compared to other treated groups. Furthermore, histopathological examination of lung tissue of intoxicated group declared an edema, air space enlargement, thick intralveolar space, numerous areas of aggregation of lymphocyte infiltration in addition to dilatation and congestion of pulmonary vein. Meanwhile treated tissue declared an obvious improvement confirming molecular results. : Data revealed, that combination of Lactobacillus and folic acid is beneficial in improving lung injury via enhancing the excretion of caddy in feces, and consequently regulates survivin, MMP-9 and JAK-2 gene expression in addition to improving damage occurred in lung tissue.