Epigenetic Programming Mediates Abnormal Gut Microbiota and Disease Susceptibility in Offspring with Prenatal Dexamethasone Exposure

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2024 Feb 1

PMID 38301654

Authors

Xiaoqian Lu

Beidi Chen

Dan Xu

Wen Hu

Xia Wang

Yongguo Dai

Qian Wang

Yu Peng

Kaiqi Chen

Dongchi Zhao

Hui Wang

Affiliations

Soon will be listed here.

Abstract

Prenatal dexamethasone exposure (PDE) can lead to increased susceptibility to various diseases in adult offspring, but its effect on gut microbiota composition and the relationship with disease susceptibility remains unclear. In this study, we find sex-differential changes in the gut microbiota of 6-month-old infants with prenatal dexamethasone therapy (PDT) that persisted in female infants up to 2.5 years of age with altered bile acid metabolism. PDE female offspring rats show abnormal colonization and composition of gut microbiota and increased susceptibility to cholestatic liver injury. The aberrant gut microbiota colonization in the PDE offspring can be attributed to the inhibited Muc2 expression caused by decreased CDX2 expression before and after birth. Integrating animal and cell experiments, we further confirm that dexamethasone could inhibit Muc2 expression by activating GR/HDAC11 signaling and regulating CDX2 epigenetic modification. This study interprets abnormal gut microbiota and disease susceptibility in PDT offspring from intrauterine intestinal dysplasia.

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