Microbial Stimulation of Oxytocin Release From the Intestinal Epithelium via Secretin Signaling

Authors

Heather A Danhof
Jihwan Lee
Aanchal Thapa
Robert A Britton
Sara C Di Rienzi

Publication Date

12-1-2023

Journal

Gut Microbes

DOI

10.1080/19490976.2023.2256043

PMID

37698879

PMCID

PMC10498800

PubMedCentral® Posted Date

9-12-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Animals, Mice, Secretin, Oxytocin, Gastrointestinal Microbiome, Gastrointestinal Hormones, Intestinal Mucosa, Limosilactobacillus reuteri, Limosilactobacillus reuteri, lactobacillus reuteri, oxytocin, secretin, enteroendocrine cells, neuropeptide hormone, gut-brain axis, enteroids, organoids, human, mouse, pig

Abstract

Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, human intestinal organoids produce oxytocin, demonstrating that the intestinal epithelium is sufficient to produce oxytocin. We find that L. reuteri facilitates oxytocin secretion from human intestinal tissue and human intestinal organoids. Finally, we demonstrate that stimulation of oxytocin secretion by L. reuteri is dependent on the gut hormone secretin, which is produced in enteroendocrine cells, while oxytocin itself is produced in enterocytes. Altogether, this work demonstrates that oxytocin is produced and secreted from enterocytes in the intestinal epithelium in response to secretin stimulated by L. reuteri. This work thereby identifies oxytocin as an intestinal hormone and provides mechanistic insight into avenues by which gut microbes promote host health.

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