Bone marrow mesenchymal stem cells synergize with fusobacterium nucleatum to drive colorectal tumorigenesis via gut microbiome dysbiosis
Abstract
The oncogenic role of F. nucleatum (Fn) in colorectal cancer (CRC) is increasingly recognized, yet its interaction with host stromal components, such as bone marrow mesenchymal stem cells (BMSCs), remains poorly understood. Building on our previous discovery that BMSC-derived Wnt3a promotes Fn-driven tumorigenesis, this study aims to investigate the synergistic interplay between BMSCs and F. nucleatum in CRC pathogenesis via the gut microbiome. Based on the established ApcMin/+ mouse model of CRC, animals were randomly assigned to four experimental groups: control, Fn-only, BMSCs-only, and Fn+BMSCs co-treatment group. Gut microbiota composition was continuously analyzed over 8 weeks by metagenomic sequencing. Metagenomic functions were predicted using PICRUSt2. The Fn+BMSCs co-treatment group exhibited the highest enrichment of F. nucleatum and the greatest reduction in microbial diversity. Fn+BMSCs co-treatment induced a distinct pro-tumorigenic shift, marked by a decline in symbiont Lactobacillus and an increase in pathobiont Escherichia-Shigella. Metagenomic analysis revealed a unique enhancement of butanoate metabolism in the Fn+BMSC co-treatment group. Furthermore, a profoundly elevated LPS level was discovered in the Fn+BMSCs co-treatment group, indicating hyperactivation of the pro-inflammatory and proliferative TLR4/NF-κB pathway. Our findings demonstrate that BMSCs synergize with F. nucleatum to create a tumorigenicmicroenvironment by driving microbial dysbiosis,…
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Evidence Hub reads this as a randomized trial. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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