RT Journal Article
SR Electronic
T1 Prenatal arsenic exposure stymies gut butyrate production and enhances gut permeability in post natal life even in absence of arsenic deftly through miR122-Occludin pathway
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.13.496028
DO 10.1101/2022.06.13.496028
A1 Chakraborty, Mainak
A1 Gautam, Anupam
A1 Das, Oishika
A1 Masid, Aaheli
A1 Bhaumik, Moumita
YR 2022
UL http://biorxiv.org/content/early/2022/06/16/2022.06.13.496028.abstract
AB This discourse attempts to capture a few important dimensions of gut physiology like microbial homeostasis, short chain fatty acid (SCFA) production, occludin expression and gut permeability in post-natal life of mice those received arsenic only during pre-natal life (pAs-mice). The pAs-mice showed a striking reduction in Firmicutes to Bacteroidetes (F/B) ratio coupled with decrease in tight junction protein, occludin resulting in increase in gut permeability, increased infiltration of inflammatory cells in the colon and decrease in common SCFAs in which butyrate reduction was quite prominent in fecal samples as compared to normal control. The above phenotypes of pAs-mice were mostly reversed by supplementing butyrate with food. The talismanic ability of butyrate in enhancing occludin expression, in particular, was dissected further. As miR122 causes degradation of Occludin mRNA, we transiently overexpressed miR122 by injecting appropriate plasmids and showed reversal of butyrate effects in pAs-mice. Thus, pre-natal arsenic exposure orchestrates variety of effects by decreasing in butyrate in pAs-mice leading to increased permeability due to reduced occludin expression. Our research adds a new dimension to our understanding that pre-natal arsenic exposure imprints in post-natal life while there was no further arsenic exposure.HighlightsPrenatal Arsenic exposure decreases prevalence of butyrate producing bacteria and butyrate production in gut.Lack of butyrate production in the gut is responsible for increased permeability and decreased occludin expression.Oral supplementation with butyrate reverses the prenatal arsenic induced changes in the gut.Butyrate increases Occludin gene expression by downregulating miR122 in the gut.Competing Interest StatementThe authors have declared no competing interest.