{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:09:04Z","timestamp":1780999744636,"version":"3.54.1"},"reference-count":63,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Education, Culture, Sports, Science, and Technology, Japan","award":["24K11118"],"award-info":[{"award-number":["24K11118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psychological stress is deeply involved in the pathophysiology of gastrointestinal diseases. We investigated the effect of psychological stress on the small-intestinal environment, including gut flora, immune system, and mucosal integrity in mice subjected to chronic social defeat stress (CSDS). CSDS mice were established by exposing a C57BL\/6N mouse to an ICR aggressor mouse. Stool samples were obtained to investigate its properties and the gut microbiome profile. Using small-intestinal tissues, the expression of cytokines, antimicrobial peptides, and tight junction proteins (TJPs) were examined by real-time RT-PCR and immunohistochemistry. Small-intestinal permeability was evaluated by transepithelial electrical resistance assay. For stool properties, mean Bristol scale score and fecal water content were significantly lower in the CSDS group. Pseudomonadota and Patescibacteria were significantly more abundant in the stools from CSDS mice. Among TJPs and antimicrobial peptides, the expression of Occludin, Claudin-4, and Regenerating gene III\u03b3 was significantly decreased in the small intestine epithelium of CSDS mice. The small-intestinal permeability was significantly increased in CSDS mice. Lipopolysaccharide immunoreactivity, the number of macrophages, and proinflammatory IL-1\u03b2 expression were significantly increased in the small intestine of CSDS mice. These findings suggest that psychological stress is associated with mucosal barrier dysfunction and microinflammation in small-intestinal tissues.<\/jats:p>","DOI":"10.3390\/ijms26199359","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:56:44Z","timestamp":1758790604000},"page":"9359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Chronic Social Defeat Stress on the Small-Intestinal Environment, Including the Gut Flora, Immune System, and Mucosal Barrier Integrity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-2950","authenticated-orcid":false,"given":"Soichi","family":"Yagi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kaku","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Wakita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8310-9767","authenticated-orcid":false,"given":"Yasuhiro","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Ikenouchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8307-2445","authenticated-orcid":false,"given":"Toshiyuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7335-6962","authenticated-orcid":false,"given":"Tetsuya","family":"Takagawa","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Education, Hyogo Medical University, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1283-9009","authenticated-orcid":false,"given":"Toshihiko","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-3083","authenticated-orcid":false,"given":"Shiho","family":"Kitaoka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hyogo Medical University School of Medicine, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-618X","authenticated-orcid":false,"given":"Shinichiro","family":"Shinzaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hyogo Medical University School of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ge, L., Liu, S., Li, S., Yang, J., Hu, G., Xu, C., and Song, W. 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