方法:食用酸奶与降低结直肠癌(CRC)的风险有关,但这种关联是否是因果关系尚不清楚.家族性腺瘤性息肉病(FAP)患者发生CRC的风险增加。这里,该研究调查了酸奶对ApcMin/小鼠肠道息肉病化学预防的功效,人类FAP的临床前模型。
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。
METHODS: Yogurt consumption is related to a decreased risk of colorectal cancer (CRC), but whether such association is causal remains unclear. Patients with familial adenomatous polyposis (FAP) are at increased risk of CRC development. Here, the study investigates the efficacy of yogurt for intestinal polyposis chemoprevention in ApcMin/+ mice, a preclinical model for human FAP.
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.