State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Cancer Cell. 2023 Aug 14;41(8):1450-1465.e8. doi: 10.1016/j.ccell.2023.06.011. Epub 2023 Jul 20.
Carnobacterium maltaromaticum was found to be specifically depleted in female patients with colorectal cancer (CRC). Administration of C. maltaromaticum reduces intestinal tumor formation in two murine CRC models in a female-specific manner. Estrogen increases the attachment and colonization of C. maltaromaticum via increasing the colonic expression of SLC3A2 that binds to DD-CPase of this bacterium. Metabolomic and transcriptomic profiling unveils the increased gut abundance of vitamin D-related metabolites and the mucosal activation of vitamin D receptor (VDR) signaling in C. maltaromaticum-gavaged mice in a gut microbiome- and VDR-dependent manner. In vitro fermentation system confirms the metabolic cross-feeding of C. maltaromaticum with Faecalibacterium prausnitzii to convert C. maltaromaticum-produced 7-dehydrocholesterol into vitamin D for activating the host VDR signaling. Overall, C. maltaromaticum colonizes the gut in an estrogen-dependent manner and acts along with other microbes to augment the intestinal vitamin D production to activate the host VDR for suppressing CRC.
发现迟缓真杆菌在女性结直肠癌（CRC）患者中特异性缺失。迟缓真杆菌的给药以雌性特异性方式减少了两种小鼠 CRC 模型中的肠道肿瘤形成。雌激素通过增加与该细菌的 DD-CPase 结合的 SLC3A2 在结肠中的表达，增加迟缓真杆菌的附着和定植。代谢组学和转录组学分析揭示了在肠道微生物组和 VDR 依赖性方式下，迟缓真杆菌灌胃小鼠中与维生素 D 相关的代谢物的肠道丰度增加和维生素 D 受体（VDR）信号的粘膜激活。体外发酵系统证实了迟缓真杆菌与粪肠球菌的代谢交叉喂养，将迟缓真杆菌产生的 7-脱氢胆固醇转化为维生素 D，以激活宿主 VDR 信号。总体而言，迟缓真杆菌以雌激素依赖性方式定植于肠道，并与其他微生物一起作用，增加肠道维生素 D 的产生，以激活宿主 VDR 抑制 CRC。
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