Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer

作者：Matthew Dietz, Travis J. Gates, Rakesh Sikdar, Subbaya Subramanian, Mikael Elias, Christopher Staley · 发表于：Cancer Medicine · 年份：2025 · DOI：10.1002/cam4.71009 · 被引用次数：3 · 研究领域：Gut microbiota and health、Cancer Research and Treatments、Probiotics and Fermented Foods

BACKGROUND: The gut microbiota is associated with colorectal cancer (CRC) risk and CRC metastatic potential. However, the role of bacteria in CRC progression and metastasis remains unclear. AIMS: Here, we hypothesized that microbial communication, mediated through quorum sensing (QS), was a critical component regulating microbial functions related to cancer progression and metastasis. MATERIALS & METHODS: To test this, male and female C57BL/6 mice were injected with organoids modeling aggressive colon cancer (CRC), carrying mutations in Apc, Kras, p53, and Smad4. Two groups of mice were treated with two different quorum quenching (QQ) lactonases (GcL or SsoPox) for 8 weeks (n = 10/group/sex). Fecal samples were collected weekly and characterized by Illumina next-generation sequencing, with tissues collected during necropsy. RESULTS: = 2.554, p = 0.110), and every female, SsoPox-treated mouse that developed a primary tumor also developed metastasis by the experimental endpoint. However, QQ treatment was shown to minimally affect the gut microbiome composition. Similarly, no significant differences were observed in inflammatory response as assessed by immunofluorescent staining or fecal concentrations of immunoglobulin A, calprotectin, or lipocalin-2. Differences in fecal short-chain fatty acid concentrations also did not differ significantly. DISCUSSION: These results suggest that QQ treatment has a sex-based effect on CRC metastatic rate. CONCLUSION: Targeting communication a...