Language

English

Publication Date

3-31-2025

Journal

The FASEB Journal

DOI

10.1096/fj.202401669R

PMID

40098558

PMCID

PMC11914943

PubMedCentral® Posted Date

3-18-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Intestinal microbes can beneficially impact host physiology, prompting investigations into the therapeutic usage of such microbes in a range of diseases. For example, human intestinal microbe Limosilactobacillus reuteri strains ATCC PTA 6475 and DSM 17938 are being considered for use for intestinal ailments, including colic, infection, and inflammation, as well as for non-intestinal ailments, including osteoporosis, wound healing, and autism spectrum disorder. While many of their beneficial properties are attributed to suppressing inflammatory responses, we postulated that L. reuteri may also regulate intestinal hormones to affect physiology within and outside of the gut. To determine if L. reuteri secreted factors impact the secretion of enteric hormones, we treated an engineered jejunal organoid line, NGN3-HIO, which can be induced to be enriched in enteroendocrine cells, with L. reuteri 6475 or 17938 conditioned medium and performed transcriptomics. Our data suggest that these L. reuteri strains affect the transcription of many gut hormones, including vasopressin and luteinizing hormone subunit beta, which have not been previously recognized as produced in the gut epithelium. Moreover, we find that these hormones appear to be produced in enterocytes, in contrast to canonical gut hormones produced in enteroendocrine cells. Finally, we show that L. reuteri conditioned media promote the secretion of enteric hormones, including serotonin, GIP, PYY, vasopressin, and luteinizing hormone subunit beta, and identify by metabolomics metabolites potentially mediating these effects on hormones. These results support L. reuteri affecting host physiology through intestinal hormone secretion, thereby expanding our understanding of the mechanistic actions of this microbe.

Keywords

Humans, Enteroendocrine Cells, Gene Expression Regulation, Hormones, Limosilactobacillus reuteri, Stress, Physiological, Transcription, Genetic, Intestines, Microbiota, adipolin, enterocyte, enteroendocrine, GIP, hormone, kisspeptin, Lactobacillus, luteinizing hormone, PYY, small intestine, vasopressin

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.