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In this study, we evaluated the impact of long-term kefir consumption on behavioral, hematological, and biochemical parameters in a mouse model displaying some PTSD-like features, particularly fear- and anxiety-related behaviors induced by acute inescapable stress. Male C57BL\/6J mice received kefir daily for 2 months before stress induction via electric foot shocks and continued supplementation for five additional months during recovery. Behavioral testing demonstrated that kefir-fed mice exhibited reduced anxiety-like behaviors, including increased exploration in the open field, elevated plus maze, and light\/dark box tests. These mice also showed fewer freezing episodes in the aversive context test, indicating attenuated fear memory. Hematological analysis revealed a modest reduction in erythrocyte count and monocytes, alongside elevated paraoxonase (PON) activity, suggesting enhanced antioxidant defense and a shift toward anti-inflammatory immune responses. RT-qPCR analysis of the cerebral cortex showed increased steady-state transcript levels of genes involved in oxidative stress response and neuroprotection (TXNRD1, UGDH, HSPB8, GADD45B, PPARGC1A) and decreased levels of the pro-inflammatory cytokine gene IL6 transcript. These results indicate that long-term kefir intake mitigates stress-induced behavioral and physiological alterations, likely through modulation of immune and oxidative stress pathways. Taken together, our findings support the potential of kefir as a functional dietary intervention for promoting stress resilience and alleviating PTSD-like symptoms, possibly via mechanisms involving the gut-brain axis.<\/jats:p>","DOI":"10.3389\/fphys.2025.1682807","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T06:22:24Z","timestamp":1763101344000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Kefir enhances stress resilience and mitigates PTSD-related behavioral and hematological changes in mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Vitalii A.","family":"Balatskyi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetiana R.","family":"Dmytriv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrii","family":"Divnych","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr I.","family":"Lushchak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1093\/nutrit\/nuad052","article-title":"Anti-inflammatory pathways of kefir in murine model: a systematic review","volume":"82","author":"Albuquerque Pereira","year":"2024","journal-title":"Nutr. 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