Association of alterations in transcriptomics and intestinal immune responses with Bifidobacterium longum BAA2573 in improving dextran sulfate sodium-induced colitis

Preliminary studies have demonstrated the potential of Bifidobacterium longum (B. longum) BAA2573 in alleviating dextran sulfate sodium (DSS)-induced colitis; however, the underlying mechanisms are still unclear. To investigate the intestinal immune responses and molecular changes upon B. Longum BAA2573 treatment. C57BL/6 J mice (6-8 weeks) were divided into three groups, control (CON), DSS, and B. longum BAA2573 intervention group (B + DSS). The B + DSS group was pretreated with B. longum BAA2573 for six days before induction with DSS. The body weight, stool characteristics, and disease activity index were recorded daily. After the 12-day intervention, the colonic tissues and serum from each group were collected for further analysis. Immunofluorescence assay was conducted to detect the infiltration of macrophages. qPCR and ELISA were used to analyze the expression of cytokines, RNA‑seq and subsequent qPCR were employed for the detection and validation of differentially expressed genes (DEGs), respectively. The crosstalk between DEGs and metabolites was also investigated. B. longum BAA2573 treatment enhanced M2-macrophage infiltration in intestinal tissues. The levels of cytokine TNF-α and IL-6 in serum were decreased, while IL-10 and TGF-β1 were significantly increased after B. longum BAA2573 pretreatment. RNA-seq identified 202 DEGs between the DSS and B + DSS group, primarily enriched in the activation of the innate immune response and phagocytosis. B. longum BAA2573 may ameliorate immune disorders in colitis mice via regulating the PI3K-AKT and NK-κB signaling pathway. Four genes, Reg3b, Rnf213, Bcl2l15, and Chp2, were significantly associated with the therapeutic effect of B. longum BAA2573. Immune-related signaling were involved in the responses to metabolic disorders. Pretreatment of B. longum BAA2573 demonstrated a promising anti-inflammatory effect in DSS-induced colitis. Supplementation of B. longum BAA2573 during UC development may represent a potential therapeutic approach by effectively maintaining intestinal immune and regulating inflammation-associated cytokines and pathways.