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In this study, homology- and cross-resistance of Lactobacillus plantarum L1 and Lactobacillus plantarum L2 to acid and osmotic stress were investigated. Meanwhile, its proliferation mechanism was demonstrated by transcriptomic analysis using RNA sequencing. We found that the homologous-resistance and cross-resistance of L. plantarum L1 and L. plantarum L2 increased after acid and osmotic induction treatment by lactic acid and sodium lactate solution in advance, and the survival rate of live bacteria was improved. In addition, the count