Probiotic Lactobacillus reuteri mitigates 5-fluorouracil-induced oral mucositis via suppression of the FTO/CMPK2/NLRP3 pathway.

BACKGROUND: (LR) may protect against 5-FU-induced OM through this pathway, yet the precise mechanism requires clarification. We aimed to investigate whether LR alleviates 5-FU-induced OM by suppressing the FTO/CMPK2/NLRP3 inflammasome pathway. Cell viability, migration, proliferation, ROS, cytokines, and mRNA/protein levels of FTO/CMPK2/NLRP3 were evaluated. LR alone and LPS alone controls were included to rule out direct effects. LR suppressed FTO/CMPK2/NLRP3 expression at mRNA and protein levels, and these effects were abolished by the NLRP3 agonist LPS. CONCLUSION: LR alleviates 5-FU-induced OM by inhibiting the FTO/CMPK2/NLRP3 inflammasome axis, reducing inflammation and oxidative stress. These findings are supported by both overexpression and knockdown experiments, as well as by human-relevant insights into LR-microbiome interactions.