Anti-inflammatory effects of vitamin K2 and Lactobacillus plantarum in a mouse model of colorectal cancer

Abstract Background Colorectal cancer (CRC) is a major health burden worldwide, and chronic inflammation plays an important role in its development and progression. The intestinal microbiota plays an important role in regulating the host immune response, and selected bacterial species may influence anticancer responses through the production of bioactive metabolites, including vitamin K2 (VK2). Previous studies have demonstrated the anti-inflammatory and potential anticancer properties of VK2 homologues and the ability of intestinal bacteria, particularly Lactobacillus , to produce VK2. We evaluated the anti-inflammatory properties of synthetic vitamin K2 (VK2) homologues (VK2-MK4, VK2-MK7, VK2-MK9) and naturally produced VK2 by Lactobacillus plantarum strain in an azoxymethane/dextran sulphate sodium (AOM/DSS) mouse model. Results BALB/c female mice were assessed clinically, histopathologically and microbiologically, with next-generation sequencing and classical culture methods used to profile gut microbiota and quantify Lactobacillus species. VK2 homologues in faeces and colonic homogenates were quantified applying UPLC-APCI-MS/MS-based method, and cytokine expression (IL-6, IL-8, TNF-α, IL-10) was analysed using immunofluorescence and western blotting. AOM/DSS-control mice exhibited chronic mucosal inflammation, glandular alterations and elevated IL-10, consistent with an immunosuppressive tumour microenvironment. VK2-MK7 and L. plantarum (VK2 natural) supplementation reduced pro-inflammatory cytokine levels, particularly IL-6, a central paracrine mediator of cancer progression, and improved IL-10 localisation, suggesting a shift towards homeostatic regulation. VK2-MK9 supplementation markedly increased Lactobacillus abundance in faeces but showed poor colonic absorption, whereas VK2-MK4 and VK2-MK7 accumulated both in faeces and colon. Despite its limited absorption, VK2-MK9 retained significant anti-inflammatory activity. All VK2 interventions demonstrated modulation of cytokine expression, potentially via NF-κB pathway inhibition. Conclusions These findings highlight the potential of specific VK2 homologues and probiotic strains to modulate inflammatory responses and gut microbiota composition, holding promise for CRC chemoprevention and adjunctive therapy.