Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants

Abstract

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.

Keywords: Apoptosis; Colorectal cancer risk; Crypt cell proliferation; Dietary fibre; Polydextrose; Resistant starch.

Graphical abstract

Fig. 1.

Effects of resistant starch (RS) and polydextrose (PD) on total mitoses post-intervention. Data are presented as individual data plots, and bars represent least squares means for data adjusted for pre-intervention total mitoses, age, sex, endoscopy procedure, BMI and smoking status (ANOVA general linear model (GLM)). Error bars represent standard errors of the mean. * Significant effect of the intervention (P < 0·05).

Fig. 2.

Differences in the effects of resistant starch supplementation on post-intervention total mitoses between younger (<50 years old) and older (≥50 years old) participants. Data are presented as individual data plots, and bars represent least squares means for data adjusted for pre-intervention total mitoses, age, sex, endoscopy procedure, BMI and smoking status (ANOVA general linear model (GLM)). Error bars represent standard errors of the mean. * Significant effect of the intervention (P < 0·05).

Fig. 3.

Positive relationship between changes in faecal (a) acetate, (b) propionate, (c) butyrate and (d) total SCFA concentrations and the change in total mitoses counts in Dietary Intervention, Stem cells and Colorectal Cancer Study participants supplemented with resistant starch.

Fig. 4.

Inverse relationship between BAX:BCL-2 and the proportion of mitotic cells in the top half of the crypt at baseline (pre-intervention). Gene expression data are presented as ratios for BAX:BCL-2 expression, expressed as adjusted copies relative to the 18S and β2M reference genes. n 41. BAX, BCL2 associated X; BCL-2, B-cell lymphoma 2.