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.
The gut microbiota plays an important role in intestinal health. Probiotics such as Lactobacillus are known to regulate gut microbes and prevent diseases. However, most of them are unable to colonize their stability in hosts’ intestinal tracts. In this study, we investigated the ability of Lactobacillus casei SY13 (SY13) to colonize the intestinal tract of BALB/c mice, after its oral administration for a short‐term (once for a day) and long‐term (once daily for 27 days) duration. Furthermore, we also evaluated the influence of its administration on the gut microbial structure and diversity in mice. Male BALB/c mice were gavaged with 108 colony‐forming units (CFU) of SY13, and TaqMan‐MGB probe and Illumina MiSeq sequencing were performed to assess the colonization ability and bacterial community structure in the cecum contents. The results showed that long‐term treatment with SY13 enhanced its ability to form a colony in the intestine tract in contrast to the short‐term treatment group, whose colony was retained for only 3 days. Oral administration of SY13 also significantly enhanced the gut microbial diversity. Short‐term treatment with SY13 (SSY13) elevated Firmicutes and diminished Bacteroidetes phyla compared with long‐term treatment (LSY13) and controls. The findings laid the foundation for the study of probiotic colonization ability and improvement of microbiota for the prevention of gut diseases.
Naturally fermented tofu whey is a nutrient-rich byproduct of tofu production that harbors diverse lactic acid bacteria (LAB) with potential probiotic properties. However, the antioxidant mechanisms of these LAB, particularly the roles of different cellular fractions and their metabolic basis, remain unclear. This study aimed to isolate LAB from naturally fermented tofu whey and evaluate their antioxidant activities across cellular fractions, combining in vitro assays, 16S rDNA-based identification, metabolomic profiling, and cellular validation to elucidate the underlying mechanisms. Six LAB strains were isolated and screened for 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radical scavenging capacity and environmental stress tolerance. Among the identified isolates, Lactiplantibacillus plantarum MCS1903 exhibited the highest extracellular antioxidant activity. Non-targeted metabolomic analysis of cell-free supernatant revealed distinct metabolic profiles compared with the MRS control, with significant enrichment of antioxidant-related metabolites and pathways. In Caco-2 cells, MCS1903 supernatant (<5%, v/v) showed no significant cytotoxicity and effectively alleviated H2O2-induced oxidative stress by modulating the Nrf2/Keap1-HO-1 signaling pathway. These findings indicate that tofu whey is a valuable source of functional LAB, and MCS1903 represents a promising candidate for probiotic and functional food applications, supporting the valorization of tofu whey and development of natural antioxidant probiotics derived from fermented food byproducts.