The gut microbiota plays important roles in chronic inflammation and colon cancer. Lactobacillus is a gut-resident probiotic with benefits to host health. We recently identified Lactobacillus plantarum strain YYC-3 with strong inhibition against two colon cancer cell lines (HT-29 and Caco2). However, the inhibitory effect of YYC-3 against colon cancer in vivo has not been verified. Thus, in the present study, we explored the probiotic function of strain YYC-3 and its cell-free supernatant (YYCS) respectively in the APCMin/+ mouse model of colon cancer during tumour development and growth, and the underlying anti-cancer mechanism. Treatment of both strain YYC-3 and the YYCS prevented the occurrence of colon tumours and mucosal damage in APCMin/+ mice fed a high-fat diet, although YYC-3 had a stronger anti-cancer effect. The mechanism involved modulation of the immune system and downregulated expression of the inflammatory cytokines interleukin (IL)-6, IL-17 F, and IL-22, along with reduced infiltration of inflammatory cells. Moreover, YYC-3 suppressed activation of the NF-κB and Wnt signalling pathways, and restored the altered gut microbiota composition to closely match that of wild-type mice. These results lay a theoretical foundation for application of YYC-3 in colon cancer prevention.

Background: Colorectal cancer (CRC) is a major clinical challenge, and the gut microbiome plays important roles in the occurrence and metastasis of CRC. Lactobacillus and their metabolites are thought to be able to suppress the growth of CRC cells. However, the antimetastatic mechanism of Lactobacillus or their metabolites toward CRC cells is not clear. Therefore, the aim of this study was to assess the inhibitory mechanism of cell-free supernatants (CFSs) of L. rhamnosus GG, L. casei M3, and L. plantarum YYC-3 on metastasis of CRC cells. Results: YYC-3 CFS showed the highest inhibitory effect on CRC cell growth, invasion and migration, and inhibited MMP2, MMP9, and VEGFA gene and protein expression, and protein secretion. Furthermore, it suppressed the activities of MMPs by gelatin zymography. Moreover, the effective compounds in these CFSs were analyzed by Q Exactive Focus liquid chromatography–mass spectrometry. Conclusions: Our results showed that metabolite secretions of YYC-3 may inhibited cell metastasis by downregulating the VEGF/MMPs signaling pathway. These data suggest that treatment of CRC cells with metabolites from L. plantarum YYC-3 may reduce colon cancer metastasis.