Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon TyneNE2 4HH, UK.
Northumbria Healthcare NHS Foundation Trust, North ShieldsNE29 8NH, UK.
Br J Nutr. 2020 Aug 28;124(4):374-385. doi: 10.1017/S0007114520001312. Epub 2020 Apr 13.
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
有强有力的证据表明,富含膳食纤维的食物可预防结直肠癌,这至少部分归因于膳食纤维的抗增殖特性。本研究旨在探究两种不可消化碳水化合物(抗性淀粉(RS)和聚右旋糖(PD))补充剂对健康个体的宏观正常直肠黏膜隐窝细胞增殖状态(CCPS)的影响。我们还研究了凋亡和细胞周期调节剂的表达与 CCPS 标志物之间的关系。75 名健康参与者参与了一项随机、双盲、安慰剂对照的 2×2 析因设计试验(饮食干预、干细胞与结直肠癌(DISC)研究),在该试验中,参与者接受 RS 和/或 PD 或安慰剂补充 50 天。在直肠黏膜活检中,通过定量 PCR 评估 CCPS,并测量细胞周期和凋亡调节剂的表达。在干预前后收集粪便样本以定量 SCFA 浓度。与安慰剂相比,RS 补充剂使隐窝内有丝分裂细胞总数增加了 60%(P=0.001)。这种作用仅限于年龄较大的参与者(≥50 岁)。与各自的对照相比,PD 或 RS 的其他处理均未观察到差异。PD 未影响任何测量变量。然而,RS 增加了老年人大肠宏观正常隐窝中的细胞增殖。我们的研究结果表明,RS 对 CCPS 的影响不仅取决于剂量、RS 类型和健康状况,还受年龄的影响。