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Our research evaluated the efficacy of a novel human breast milk\u2010derived probiotic strain,\n                      <jats:italic>Bifidobacterium breve (B. breve<\/jats:italic>\n                      ) SHMB 8001, against colitis in mice following dextran sulfate sodium (DSS) challenge and elucidated its molecular basis.\n                      <jats:italic>B. breve<\/jats:italic>\n                      SHMB 8001 administration alleviated DSS\u2010induced alterations in body mass, disease activity index (DAI), colon dimensions (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.007), and tissue histology (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). SHMB 8001 increased the colonic levels of critical barrier proteins MUC2 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), occludin (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), and claudin\u20101 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), as measured by qPCR and western blotting. SHMB 8001 significantly elevated the levels of fecal short\u2010chain fatty acids (SCFAs) and colonic G protein\u2010coupled receptor (GPR) 43 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.023) and the percentage of CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      Treg cells (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.009), as determined by gas chromatography\u2013mass spectrometry (GC\u2013MS), qPCR, and flow cytometry, respectively. Furthermore, qPCR revealed that SHMB 8001 up regulated the colonic expression of interleukin (IL)\u201010 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.010) but suppressed the expression of IL\u20101\u03b2 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.013), IL\u20106 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.005), and tumor necrosis factor (TNF)\u2010\u03b1 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.021). High\u2010throughput 16S rRNA gene sequencing revealed that SHMB 8001 modulated the composition of the gut micro biota by enriching bacterial genera capable of producing SCFAs, including\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      ,\n                      <jats:italic>norank_f_Muribaculaceae<\/jats:italic>\n                      , and\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      , and partially restored the microbial functional pathways altered by DSS. In conclusion, this study demonstrates that\n                      <jats:italic>B. breve<\/jats:italic>\n                      SHMB 8001 represents a potential probiotic strain for alleviating colitis by normalizing intestinal homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Practical Applications<\/jats:title>\n                    <jats:p>\n                      This research evaluated the efficacy of a novel human breast milk\u2010derived probiotic strain,\n                      <jats:italic>B. breve<\/jats:italic>\n                      SHMB 8001, against colitis in mice following dextran sulfate sodium (DSS) challenge, and delineated its molecular basis.\n                      <jats:italic>B. breve<\/jats:italic>\n                      SHMB 8001 represents a potential probiotic strain for alleviating colitis via normalizing intestinal homeostasis.\n                    <\/jats:p>\n             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