{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T08:24:17Z","timestamp":1767774257733,"version":"build-2238731810"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Maresin1 (MaR1), a specialized pro-resolving mediator derived from docosahexaenoic acid (DHA), exerts potent anti-inflammatory and cytoprotective actions. Its therapeutic relevance and underlying mechanisms in intestinal ischemia\u2013reperfusion (I\/R) injury remain to be fully defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A murine I\/R model was generated by transient occlusion of the superior mesenteric artery. Retinoic acid receptor-related orphan receptor alpha (ROR\u03b1) and gasdermin D (GSDMD) knockout mice were used to interrogate signaling pathways. Mice received intraperitoneal MaR1 or dietary supplementation with DHA and\/or\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      (Lact). Intestinal injury, inflammation, and pyroptosis were assessed by histology, biochemical markers, and Western blotting. Integrated 16S rRNA sequencing, transcriptomics, and metabolomics characterized microbiota composition, host transcriptional profiles, and metabolic shifts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MaR1 significantly limited epithelial injury and inhibited pyroptosis through ligand-dependent activation of ROR\u03b1, effects abolished in\n                      <jats:italic>Ror\u03b1<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      and\n                      <jats:italic>Gsdmd<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice. DHA supplementation elevated systemic MaR1 levels and reproduced protective effects against I\/R damage. Remarkably, combined DHA and\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      supplementation provided synergistic benefits, as\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      enhanced DHA-to-MaR1 conversion. Multi-omics analyses confirmed coordinated modulation of inflammatory networks and microbial metabolic activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MaR1 and its precursor DHA confer robust protection against intestinal I\/R injury by suppressing ROR\u03b1-driven pyroptosis. The probiotic-mediated amplification of MaR1 biosynthesis highlights a novel microbiota\u2013lipid mediator crosstalk with translational potential. These findings support combinatorial interventions leveraging host\u2013microbe interactions as a promising therapeutic avenue for ischemic intestinal injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1712761","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T06:33:17Z","timestamp":1765521197000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactobacillus amplifies DHAMaR1 conversion to attenuate intestinal ischemia-reperfusion injury via decreasing 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