Transcriptomic Analysis of Probiotic Oxidative Stress Resistance in Anti-inflammatory Pathways

Oxidative stress caused by reactive oxygen species such as H₂O₂ and HOCl plays a central role in inflammation-related diseases. This study aimed to identify key genes and biological pathways that enable probiotics to tolerate oxidative stress, using transcriptomic analysis of E. coli, L. plantarum, and L. reuteri under exposure to H₂O₂ and HOCl. We retrieved three related probiotics datasets from the Gene Expression Omnibus (GEO) database and the Sequence Read Archive (SRA) databases, including Lactobacillus plantarum (GSE99096), Lactobacillus reuteri (GSE127961), and Escherichia coli (GSE144068). We used the CLC Genomics Workbench software to identify the differentially expressed genes (DEGs) and then applied STRING 11.5 to identify the interactions between the DEGs. The CytoHubba was used to determine the hub genes in the interactive networks. We assessed the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of hub genes and evaluated the associated biological pathways. Among the identified hub genes, GuaA and Tig in E. coli were found to be uniquely involved in purine metabolism and ribosome assembly, highlighting novel targets for oxidative stress resistance. In addition, ComEA in L. plantarum and UvrB, Mfd and GrpE in L. reuteri represent diverse molecular strategies used by probiotics to cope with oxidative stress. These genes were associated with key pathways such as purine metabolism, mismatch repair, nucleotide excision repair and the pentose phosphate pathway. These critical genes and biological pathways can be used to improve the efficacy of probiotics in treating inflammatory diseases.