Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan.
Field of Basic Science, Department of Occupational Therapy, Akita University Graduate School of Health Science, Akita 010-8543, Japan.
Int J Mol Sci. 2022 Feb 17;23(4):2214. doi: 10.3390/ijms23042214.
Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.
猪油饮食（LD）是前列腺癌（PCa）发展和进展的危险因素。两种具有免疫能力的小鼠模型，喂食等热量的特定脂肪饮食（LD），富含饱和和单不饱和脂肪酸（SMFA），与鱼油饮食（FOD）相比，体重增加显著促进了 PCa 的进展。由于饮食的差异，肠道微生物多样性显著增加，而在 LD 或 FOD 喂养的小鼠粪便中，几种细菌的丰度，如梭状芽胞杆菌和乳杆菌目，明显改变。肠道中乳杆菌目细菌的比例与 SMFA 诱导的体重增加和 PCa 进展呈负相关。我们发现，三种和七种常见的上调和下调基因在 PCa 组织中参与了脂质代谢和胆固醇生物合成途径的调节，其中一些与肠道中乳杆菌目细菌的丰度相关。与乳杆菌目和小鼠模型中的癌症进展相关的神经鞘氨醇 1-磷酸受体 2的表达，与使用 NCBI 基因表达综合数据库的 PCa 患者的侵袭性表型和体重增加呈负相关。因此，SMFA 可能通过特定肠道微生物物种的丰度和 PCa 中脂肪生成基因的过度表达促进 PCa 的进展。改变肠道微生物群和与饮食诱导的 PCa 进展相关的候选基因的治疗方法可能对 PCa 有吸引力。
