RESULTS: A 10-week yogurt supplementation (15 g kg-1) in ApcMin/+ mice significantly reduces the intestinal polyp number (6.50 ± 0.97 versus 1.80 ± 0.49; p < 0.001) compared to controls. 16S rRNA gene-based microbiota analysis suggests that yogurt supplementation may greatly modulate the gut microbiome composition, especially in the relative abundance of Lactobacillus and Bifidobacterium. Importantly, the fecal concentration of d-lactate (d-Lac, 0.39 ± 0.04 µmol g-1 versus 8.14 ± 0.62 µmol g-1; p < 0.001) is boosted by yogurt, while oral administration with d-Lac (125 or 250 mg kg-1) reduces the polyp number by 71.43% or 77.14% (p < 0.001), respectively. The study also observes that d-Lac does not affect cell viability and anchorage-independence in CRC cells, but it greatly suppresses epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in preneoplastic cells. Mechanistically, it demonstrates that d-Lac may attenuate epithelial cell transformation by targeting PI3K/AKT/β-catenin axis.
CONCLUSIONS: Yogurt protects against intestinal polyposis in ApcMin/+ mice, and d-Lac may partially account for the chemopreventive effects above.
结果:与对照组相比,ApcMin/+小鼠补充10周酸奶(15gkg-1)显着降低了肠息肉数量(6.50±0.97对1.80±0.49;p<0.001)。基于16SrRNA基因的微生物群分析表明,补充酸奶可能会极大地调节肠道微生物组组成,特别是在乳酸菌和双歧杆菌的相对丰度。重要的是,d-乳酸的粪便浓度(d-Lac,0.39±0.04µmolg-1与8.14±0.62µmolg-1;p<0.001)由酸奶增强,口服d-Lac(125或250mgkg-1)可使息肉数量减少71.43%或77.14%(p<0.001),分别。该研究还观察到d-Lac不会影响CRC细胞的细胞活力和锚定独立性。但它极大地抑制了肿瘤前细胞中表皮生长因子(EGF)或12-O-十四烷酰基佛波醇-13-乙酸酯(TPA)诱导的细胞转化。机械上,它表明d-Lac可能通过靶向PI3K/AKT/β-catenin轴来减弱上皮细胞转化。
结论:酸奶可以预防ApcMin/+小鼠的肠息肉病,和d-Lac可能部分解释上述化学预防作用。