Abstract

Background: Psychological stress alters the gut microbiota and predisposes individuals to increased risk for enteric infections and chronic bowel conditions. Intestinal epithelial cells (IECs) are responsible for maintaining homeostatic interactions between the gut microbiota and its host. In this study, we hypothesized that disruption to colonic IECs is a key factor underlying stress-induced disturbances to intestinal homeostasis. Methods: Conventionally-raised (CONV-R) and germ-free (GF) mice were exposed to a social disruption stressor (Str) to ascertain how stress modifies colonic IECs, the mucosal layer, and the gut microbiota. Findings: RNA sequencing of IECs isolated from conventionally-reared (CONV-R) mice revealed a robust pro-inflammatory (Saa1, Il18), pro-oxidative (Duox2, Nos2), and antimicrobial (Reg3g, Reg3b) transcriptional profile as a result of Str. This response occurred concomitant to thinning of the mucus layer and signs of systemic endotoxemia. In contrast to their CONV-R counterparts, IECs from GF mice exhibited no detectable transcriptional changes in response to Str. Still, IECs from Str-exposed GF mice exhibited an altered response to ex vivo bacterial challenge (increased Dual Oxidase-2 [DUOX2]), indicating a priming event by host stress signals. Stress-induced increase in colonic DUOX2 in CONV-R mice paralleled changes to catalase positive bacteria and luminal catalase activity, evidencing Str-mediated disruptions in gut microbiota function through excessive IEC ROS production. Interpretation: Social stress disrupts colonic epithelial cells and mucosal integrity, a response dependent on an intact microbiota and endogenous stress signal priming. Funding: This work was supported by a Ruth L. Kirschstein National Research Service T32DE014320 to J. Allen, NIH grant AT006552-01A1 to M. Bailey, and internal funding from the Abigail Wexner Research Institute at Nationwide Children’s Hospital to J. Allen and M. Bailey. Declaration of Interest: The authors report no competing interests. Ethical Approval: All animals used in this study were approved by the IACUC at Nationwide Children’s Hospital.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call