AlHilli Mariam M, Sangwan Naseer, Myers Alex, Tewari Surabhi, Lindner Daniel J, Cresci Gail A M, Reizes Ofer
Department of Subspeciality Care for Women's Health, Division of Gynecologic Oncology, Obstetrics and Gynecology Institute, Cleveland Clinic, 9500 Euclid Avenue A81, Cleveland, OH, 44115, USA.
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
J Ovarian Res. 2025 Aug 2;18(1):174. doi: 10.1186/s13048-025-01731-1.
The gut microbiome (GM) is pivotal in regulating inflammation, immune responses, and cancer progression. This study investigates the effects of a ketogenic diet (KD) and a high-fat/low-carbohydrate (HF/LC) diet on GM alterations and tumor growth in a syngeneic mouse model of high-grade serous ovarian cancer (EOC).
Thirty female C57BL/6 J mice injected with KPCA cells were randomized into KD, HF/LC, and low-fat/high-carbohydrate (LF/HC) diet groups. Tumor growth was monitored with live, in vivo imaging. Stool samples were collected at the time of euthanasia and analyzed by 16SrRNA sequencing and shotgun metagenomic sequencing was performed to identify differential microbial taxonomic composition and metabolic function.
Our findings revealed that KD and HF/LC diets significantly accelerated EOC tumor growth compared to the LF/HC diet in a xenograft model. GM diversity was markedly reduced in KD and HF/LC-fed mice, correlating with increased tumor growth, whereas LF/HC-fed mice showed higher GM diversity. Metagenomic analyses identified distinct alterations in microbial taxa including Bacteroides, Lachnospiracae bacterium, Bacterium_D16_50, and Enterococcus faecalis predominantly abundant in HF/LC-fed mice, Dubsiella_newyorkensis predominantly abundant in LF/HC-fed, and KD fed mice showing a higher abundance of Akkermansia and Bacteroides. Functional pathways across diet groups indicated polyamine biosynthesis and fatty acid oxidation pathways were enriched in HF/LC-fed mice.
These results highlight the intricate relationship between diet andthe gut microbiome in promoting EOC growth. The potential role of dietary interventions in cancer prevention and treatment warrants further investigation.
肠道微生物群（GM）在调节炎症、免疫反应和癌症进展中起关键作用。本研究在高级别浆液性卵巢癌（EOC）的同基因小鼠模型中，研究生酮饮食（KD）和高脂肪/低碳水化合物（HF/LC）饮食对GM改变和肿瘤生长的影响。
将30只注射了KPCA细胞的雌性C57BL/6 J小鼠随机分为KD、HF/LC和低脂/高碳水化合物（LF/HC）饮食组。通过活体体内成像监测肿瘤生长。在安乐死时收集粪便样本，并通过16SrRNA测序进行分析，同时进行鸟枪法宏基因组测序以确定微生物分类组成和代谢功能的差异。
我们的研究结果显示，在异种移植模型中，与LF/HC饮食相比，KD和HF/LC饮食显著加速了EOC肿瘤的生长。KD和HF/LC喂养的小鼠GM多样性明显降低，这与肿瘤生长增加相关，而LF/HC喂养的小鼠GM多样性较高。宏基因组分析确定了微生物分类群的明显变化，包括HF/LC喂养的小鼠中主要丰富的拟杆菌属、毛螺菌科细菌、细菌_D16_50和粪肠球菌，LF/HC喂养的小鼠中主要丰富的纽约杜氏菌，以及KD喂养的小鼠中阿克曼氏菌和拟杆菌属的丰度较高。不同饮食组的功能途径表明，HF/LC喂养的小鼠中多胺生物合成和脂肪酸氧化途径富集。
这些结果突出了饮食与肠道微生物群在促进EOC生长中的复杂关系。饮食干预在癌症预防和治疗中的潜在作用值得进一步研究。
