{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:51:10Z","timestamp":1789404670327,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea government","award":["RS-2024-00486802"],"award-info":[{"award-number":["RS-2024-00486802"]}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Science and ICT, Korea","doi-asserted-by":"publisher","award":["2017R1A5A2014768"],"award-info":[{"award-number":["2017R1A5A2014768"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Sleeplessness (insomnia) is a significant symptom associated with stress-induced depression\/anxiety. In the present study, we selected Bifidobacterium longum P77, which increased serotonin production in corticosterone-stimulated SH-SY5Y cells, from the fecal bacteria collection of healthy volunteers and examined the effects of B. longum on depression, anxiety, and sleeplessness induced by immobilization stress or by transplantation of cultured fecal microbiota (cFM) from patients with depression. Orally administered B. longum P77 decreased depression\/anxiety- and sleeplessness-like behaviors in immobilization stress-exposed mice. B. longum P77 reduced immobilization stress-induced corticosterone, tumor necrosis factor (TNF)-\u03b1, and interleukin (IL)-6 expression and the cell population of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB)+ in the prefrontal cortex, while the expression levels of immobilization stress-suppressed IL-10, \u03b3-aminobutyric acid (GABA), its receptor GABAAR\u03b11, serotonin, and its receptor 5-HT1AR increased. B. longum P77 also alleviated immobilization stress-induced colitis: it decreased TNF-\u03b1 and IL-6 expression and increased IL-10 expression in the colon. Furthermore, B. longum P77, Lactiplantibacillus plantarum P72, and their combination decreased cFM- or immobilization stress-induced depression-, anxiety-, and sleeplessness-like behaviors. They also decreased cFM-induced, corticosterone, TNF-\u03b1, and IL-6 expression levels in the prefrontal cortex and colon, while increasing cFM- or immobilization stress-suppressed GABA, GABAAR\u03b11, serotonin, and 5-HT1AR expression levels in the prefrontal cortex. In particular, the combination of B. longum P77 and L. plantarum P72 (P7277) additively or synergistically alleviated depression-, anxiety-, and sleeplessness-like behaviors, along with their associated biomarkers. Heat-killed P7277 also alleviated immobilization stress-induced depression\/anxiety- and sleeplessness-like symptoms. These results imply that L. plantarum P72 and\/or B. longum P77 can mitigate depression\/anxiety and sleeplessness by upregulating GABAergic and serotonergic systems, along with the suppression of NF-\u03baB activation.<\/jats:p>","DOI":"10.3390\/cells14191547","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T11:53:37Z","timestamp":1759492417000},"page":"1547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bifidobacterium longum P77 and Lactiplantibacillus plantarum P72 and Their Mix\u2014Live or Heat-Treated\u2014Mitigate Sleeplessness and Depression in Mice: Involvement of Serotonergic and GABAergic Systems"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0767-8342","authenticated-orcid":false,"given":"Ji-Su","family":"Baek","sequence":"first","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8198-6785","authenticated-orcid":false,"given":"Xiaoyang","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Seo","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9272-6260","authenticated-orcid":false,"given":"Dong-Yun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1159\/000442929","article-title":"Psychological Stress and Depression: Risk Factors for IBD?","volume":"34","author":"Bernstein","year":"2016","journal-title":"Dig. 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