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bioRxiv · 10.1101/2022.06.13.496028

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.

CHAKRABORTY, M.·GAUTAM, A.·DAS, O.·MASID, A.·BHAUMIK, M.
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Abstract

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. HighlightsO_LIPrenatal Arsenic exposure decreases prevalence of butyrate producing bacteria and butyrate production in gut. C_LIO_LILack of butyrate production in the gut is responsible for increased permeability and decreased occludin expression. C_LIO_LIOral supplementation with butyrate reverses the prenatal arsenic induced changes in the gut. C_LIO_LIButyrate increases Occludin gene expression by downregulating miR122 in the gut. C_LI

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CHAKRABORTY, M., GAUTAM, A., DAS, O., MASID, A., BHAUMIK, M.. 2022-06-16. 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.. https://doi.org/10.1101/2022.06.13.496028

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