Alberts David S, Einspahr Janine G, Earnest David L, Krutzsch Mary F, Lin Po, Hess Lisa M, Heddens David K, Roe Denise J, Martínez Maria Elena, Salen Gerald, Batta A K
Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724-5024, USA.
Cancer Epidemiol Biomarkers Prev. 2003 Mar;12(3):197-200.
Factors that affect the concentration of secondary bile acids in the aqueous phase of stool may have a greater impact on colon carcinogenesis than those that only modify the total fecal bile acid concentration. This hypothesis was tested using stool samples of a subset of participants enrolled in a Phase III colorectal adenomatous polyp prevention trial, which documented the inability of a 13.5 g/day wheat bran fiber (WBF) supplement to reduce polyp recurrence. Stool was collected from 68 consecutively consented participants who were enrolled in a Phase III clinical trial of WBF for the prevention of adenomatous polyp recurrence. Nineteen (27.9%) of these fecal bile acid substudy participants were on the low fiber (2.0 g/day) intervention group, whereas 49 (72.7%) were on the high fiber (13.5 g/day) intervention group for approximately 3 years. Sixty-four participants had both the aqueous and solid phases of stool samples analyzed for bile acid content. Bile acid concentrations, measured in microg/ml for fecal water and microg/mg for dry feces, were determined for lithochilic, deoxycholic, chenodeoxycholic, cholic, ursodeoxycholic, isodeoxycholic, isoursodeoxycholic, ursocholic, 7-ketolithocholic, and 12-ketolithocholic acids. There were no significant differences between the low and high fiber groups concerning mean or median aqueous phase concentrations of lithocholic or deoxycholic bile acids. In contrast, the median concentrations of deoxycholic acid and other secondary bile acids (including lithochilic, isodeoxycholic, ursodeoxycholic, isoursodeoxycholic, ursocholic, 7-ketolithocholic, and 12-ketolithocholic acids) were significantly lower for the high fiber group in the solid-phase stool (P < 0.05). These results document that a high WBF intervention, taken for a median of 2.4 years, does not significantly reduce aqueous-phase concentrations of secondary bile acids in stool, although their concentrations in solid-phase stool were suppressed. Thus, the inability of the high WBF intervention to reduce colorectal adenoma recurrence may be a consequence of its lack of effect on fecal aqueous-phase secondary bile acid concentrations.
影响粪便水相中次级胆汁酸浓度的因素,可能比那些仅改变粪便总胆汁酸浓度的因素对结肠癌发生的影响更大。这一假设通过对参加一项III期结直肠腺瘤性息肉预防试验的部分参与者的粪便样本进行检测得以验证,该试验记录了每日补充13.5克麦麸纤维(WBF)无法降低息肉复发率。从68名连续同意参与WBF预防腺瘤性息肉复发III期临床试验的参与者中收集粪便。这些粪便胆汁酸子研究参与者中,19人(27.9%)在低纤维(每日2.0克)干预组,而49人(72.7%)在高纤维(每日13.5克)干预组,持续约3年。64名参与者的粪便样本水相和固相均进行了胆汁酸含量分析。测定了石胆酸、脱氧胆酸、鹅脱氧胆酸、胆酸、熊去氧胆酸、异脱氧胆酸、异熊去氧胆酸、熊胆酸、7-酮石胆酸和12-酮石胆酸的胆汁酸浓度,粪便水相以微克/毫升为单位,干粪便以微克/毫克为单位。低纤维组和高纤维组在石胆酸或脱氧胆酸水相平均浓度或中位数浓度方面无显著差异。相比之下,高纤维组固相粪便中脱氧胆酸和其他次级胆汁酸(包括石胆酸、异脱氧胆酸、熊去氧胆酸、异熊去氧胆酸、熊胆酸、7-酮石胆酸和12-酮石胆酸)的中位数浓度显著较低(P<0.05)。这些结果表明,为期中位数2.4年的高WBF干预虽可抑制粪便固相中的次级胆汁酸浓度,但并未显著降低粪便水相中次级胆汁酸的浓度。因此,高WBF干预无法降低结直肠腺瘤复发率,可能是其对粪便水相次级胆汁酸浓度缺乏影响的结果。