OSCR

Environmental enrichment attenuates chronic stress-induced disruptions in the gut microbiota, intestinal barrier, and brain.

Overview

Authors: Seung Ju Kang1, Hyeong Ju Nam1, Min Kyung Song1
ORCID iDs: Min Kyung Song
  1. College of Nursing Science, Kyung Hee University, Seoul, Republic of Korea
Institutions: Kyung Hee University (South Korea)
Journal: PloS one, volume 21, issue 8, article e0355857
Dates: received 22 January 2026; accepted 27 July 2026; published online 14 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1371/journal.pone.0355857 · PMID 42599964 · PMCID PMC13475964 · OpenAlex W7203480409
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), depression (population), cellular / molecular (subfield)
Methods: Statistics
MeSH: Brain*, Environment*, Gastrointestinal Microbiome*, Stress, Psychological*, Animals, Depression, Intestinal Barrier Function, Male, Mice, Mice, Inbred C57BL (* major topic)
Journal subjects: Biology and Life Sciences, Organisms, Bacteria, Gut Bacteria, Medicine and Health Sciences, Mental Health and Psychiatry, Mood Disorders, Depression, Anatomy, Digestive System, Gastrointestinal Tract, Psychology, Behavior, Animal Behavior, Collective Animal Behavior, Social Sciences, Zoology, Research and Analysis Methods, Animal Studies, Experimental Organism Systems, Model Organisms, Mouse Models, Animal Models, Immunology, Immune Response, Inflammation, Clinical Medicine, Signs and Symptoms, Psychological Stress
Topic: Gut microbiota and health (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Citations: not cited yet (Europe PMC); 85 references in the paper

Abstract

Major depressive disorder is a prevalent mood disorder characterized by affective and cognitive impairment. Alterations in gut microbiota have been implicated in its pathophysiology, as stress-related microbial changes can disrupt intestinal barrier integrity and promote inflammatory activation along the microbiota–gut–brain axis. Although environmental enrichment (EE) has been shown to exert beneficial effects on stress-related behaviors, its influence on gut microbiota under chronic stress conditions remains unclear. Here, we examined the effects of EE on depressive-like behavior, stress-related molecular markers in the brain, gut microbiota composition, and intestinal barrier function in a chronic unpredictable mild stress (CUMS) mouse model. Following CUMS exposure for 5 weeks, mice were housed in either a standard environment or EE for 4 weeks. EE significantly reduced immobility time in the tail suspension test and restored tryptophan hydroxylase‑positive cell numbers in the dorsal raphe nucleus while reversing glucocorticoid receptor‑positive cell expression in the hippocampus. Microbiota analysis revealed that CUMS elevated alpha diversity and altered beta diversity, accompanied by increases in stress‑associated taxa—including Firmicutes, Desulfobacterota, Patescibacteria, and Ruminococcus—and reductions in beneficial taxa such as Akkermansia. EE prevented the CUMS-induced alterations, reestablishing microbial diversity and community structure toward control levels and partially reversing the taxonomic changes. In the colon, CUMS reduced claudin‑1 expression and increased IL‑6 and NF‑κB protein levels, reflecting impaired barrier integrity and enhanced inflammatory responses. EE attenuated the CUMS-induced intestinal disruptions, restoring tight junction protein expression and reducing inflammatory markers. In conclusion, EE may serve as a non‑pharmacological intervention capable of stabilizing the microbiota–gut–brain axis in depressive‑like states.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Data links

Data Availability

All relevant data are within the manuscript and its Supporting Information files. The raw sequencing reads have been deposited in the NCBI Sequence Read Archive (SRA) under BioProject PRJNA1443475. (https://www.ncbi.nlm.nih.gov/bioproject/ PRJNA1443475).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 10 MeSH terms, 1 funder, 85 references.

Cite

This paper

Kang, S. J., Nam, H. J., & Song, M. K. (2026). Environmental enrichment attenuates chronic stress-induced disruptions in the gut microbiota, intestinal barrier, and brain. PloS one, 21(8), e0355857. https://doi.org/10.1371/journal.pone.0355857

BibTeX

@article{kang2026environmental,
author = {Kang, Seung Ju and Nam, Hyeong Ju and Song, Min Kyung},
title = {{Environmental enrichment attenuates chronic stress-induced disruptions in the gut microbiota, intestinal barrier, and brain}},
journal = {PloS one},
year = {2026},
month = aug,
volume = {21},
number = {8},
pages = {e0355857},
publisher = {PLOS},
issn = {1932-6203},
doi = {10.1371/journal.pone.0355857},
url = {https://doi.org/10.1371/journal.pone.0355857},
pmid = {42599964},
pmcid = {PMC13475964}
}

RIS

TY - JOUR
AU - Kang, Seung Ju
AU - Nam, Hyeong Ju
AU - Song, Min Kyung
TI - Environmental enrichment attenuates chronic stress-induced disruptions in the gut microbiota, intestinal barrier, and brain
T2 - PloS one
J2 - PLoS One
PY - 2026
DA - 2026/08/14
VL - 21
IS - 8
SP - e0355857
SN - 1932-6203
PB - PLOS
DO - 10.1371/journal.pone.0355857
UR - https://doi.org/10.1371/journal.pone.0355857
LA - en
ER -

CSL-JSON

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