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Inflammatory bowel disease (IBD) is a recurring inflammatory disease of the gastrointestinal tract with unclear etiology, but it is thought to be related to factors like immune abnormalities and gut microbial dysbiosis. Probiotics can regulate host immunity and gut microbiota; thus, we investigated the alleviation effect and mechanism of the strain Lactobacillus gasseri G098 (G098) on dextran sodium sulfate (DSS)-induced colitis in mice. Three groups of mice (n = 8 per group) were included: normal control (NC), DSS-induced colitis mice (DSS), and colitis mice given strain (G098). Our results showed that administering G098 effectively reversed DSS-induced colitis-associated symptoms (mitigating weight loss, reducing disease activity index and pathology scores; p < 0.05 in all cases) and prevented DSS-induced mortality (62.5% in DSS group; 100% in G098 group). The mortality rate and symptom improvement by G098 administration was accompanied by a healthier serum cytokine balance (significant decreases in serum pro-inflammatory factors, interleukin (IL)-6 [p < 0.05], IL-1β [p < 0.01], and tumor necrosis factor (TNF)-α [p < 0.001], and significant increase in the serum anti-inflammatory factor IL-13 [p < 0.01], compared with DSS group) and gut microbiome modulation (characterized by a higher gut microbiota diversity [p < 0.05], significantly more Firmicutes and Lachnoclostridium [p < 0.05], significantly fewer Bacteroidetes [p < 0.05], and significant higher gene abundances of sugar degradation-related pathways [p < 0.05], compared with DSS-treated group). Taken altogether, our results suggested that G098 intake could mitigate DSS-induced colitis through modulating host immunity and gut microbiome, and strain treatment is a promising strategy for managing IBD.