A high-fat diet (HFD) may be linked to an increased colorectal cancer (CRC) risk. Stem cell proliferation and adipokine release under inflammatory and obese conditions are the main factors regulating CRC progression. Furthermore, alterations in intestinal flora have been linked to tumorigenesis and tumour progression. However, whether a HFD can promote CRC occurrence by altering intestinal flora remains unclear. The objective of this study was to identify bacterial strains enriched by a HFD and investigate the association and mechanism by which a HFD and bacterial enrichment promote CRC occurrence and development. In this study, the intestinal microbiota of mice was assessed using 16S rRNA and metagenomic sequencing. Serum metabolites of HFD-fed mice were assessed using tandem liquid chromatography-mass spectrometry. CRC cell lines and organoids were co-cultured with Coriobacteriaceae to evaluate the effect of these bacteria on the CPT1A-ERK signalling pathway. We found that Coriobacteriaceae were enriched in the colons of HFD-fed mice. An endogenous Coriobacteriaceae strain, designated as Cori.ST1911, was successfully isolated and cultured from the stools of HFD-fed mice, and the tumorigenic potential of Cori.ST1911 in CRC was validated in several CRC mouse models. Furthermore, Cori.ST1911 increased acylcarnitine levels by activating CPT1A, demonstrating the involvement of the CPT1A-ERK axis. We also found that the endogenous Lactobacillus strain La.mu730 can interfere with Cori.ST1911 colonisation and restore gut barrier function. In conclusion, we identified a novel endogenous intestinal Coriobacteriaceae, Cori.ST1911, which might lead to a new gut microbiota intervention strategy for the prevention and treatment of CRC.

高脂肪饮食（HFD）可能与结直肠癌（CRC）风险增加有关。炎症和肥胖条件下的干细胞增殖和脂肪因子释放是调节CRC进展的主要因素。此外，肠道菌群的改变与肿瘤发生和进展有关。然而，高脂饮食是否可以通过改变肠道菌群促进结直肠癌的发生仍不清楚。本研究的目的是鉴定 HFD 富集的细菌菌株，并研究 HFD 和细菌富集促进 CRC 发生和发展的关联和机制。在这项研究中，使用 16S rRNA 和宏基因组测序评估了小鼠的肠道微生物群。使用串联液相色谱-质谱法评估 HFD 喂养小鼠的血清代谢物。将 CRC 细胞系和类器官与Coriobacteriaceae共培养，以评估这些细菌对 CPT1A-ERK 信号通路的影响。我们发现高脂饮食小鼠的结肠中富含Coriobacteriaceae 。从高脂饮食小鼠的粪便中成功分离和培养了一种内源性Coriobacteriaceae菌株，命名为Cori .ST1911，并在几种 CRC 小鼠模型中验证了Cori .ST1911 在 CRC 中的致瘤潜力。此外，Cori .ST1911 通过激活 CPT1A 增加酰基肉碱水平，证明 CPT1A-ERK 轴的参与。我们还发现内源性乳杆菌菌株La.mu 730 可以干扰Cori .ST1911 定植并恢复肠道屏障功能。总之，我们鉴定了一种新型内源性肠道Coriobacteriaceae Cori.ST1911 ，它可能为预防和治疗 CRC 带来新的肠道微生物群干预策略。