Lactiplantibacillus plantarum HNU082 inhibited the growth of Fusobacterium nucleatum and alleviated the inflammatory response introduced by F. nucleatum invasion.

As a potential biomarker, there is increasing evidence showing that Fusobacterium nucleatum is positively correlated with the occurrence and development of colorectal cancer. Although antibiotics were expected to eliminate F. nucleatum, the side effects associated with gut microbiotal disorders have to be considered. Here, by performing shotgun metagenomic and transcriptome sequencing, we systematically evaluated the antagonistic effects of probiotic Lactiplantibacillus plantarum HNU082 (Lp082) on F. nucleatum in vivo and in vitro. The results showed that the F. nucleatum invasion significantly altered the host intestinal microbiome including the microbial composition, specific species, metabolic pathways and metabolites, as well as impacted the transcriptome of the intestinal epithelial cells. Moreover, the F. nucleatum invasion triggered inflammatory cytokines and inflammatory responses in the intestine but did not develop into colorectal cancer. Excitingly, the Lp082 intervention inhibited the growth of F. nucleatum both in vivo and in vitro and alleviated the inflammatory response introduced by F. nucleatum invasion. Further network-based mechanism exploration demonstrated that Lp082, which negatively correlated to F. nucleatum, maintained the intestinal microbiome homeostasis and prompted the production of beneficial metabolites in the intestine which decreased the expression of inflammatory cytokines in a mouse model. The present research suggested a feasible probiotic intervention strategy for F. nucleatum antagonism in vivo, which may prevent colorectal cancer at the early stage.