Plasma, urine, and stool metabolites in response to dietary rice bran and navy bean supplementation in adults at high-risk for colorectal cancer.

Emily B Hill, Bridget A Baxter, Brigitte Pfluger, Caroline K Slaughter, Melanie Beale, Hillary V Smith, Sophia S Stromberg, Madison Tipton, Hend Ibrahim, Sangeeta Rao, Heather Leach, Elizabeth P Ryan
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Abstract

Introduction: Dietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC.

Methods: Adults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol®-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure via 16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure.

Results: Across biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p<0.001) and a 3.33-fold difference in urine (p=0.008) for the amino acid S-methylcysteine at 12 weeks. Fold-differences to 4-methoxyphenol sulfate in plasma and urine after 6 and 12 weeks (p<0.001) was a novel result from this combined rice bran and navy bean intervention in people. A 2.98-fold difference in plasma (p=0.002) and a 17.74-fold difference in stool (p=0.026) was observed for the lipid octadecenedioylcarnitine at 12 weeks. For stool BAs, 3-oxocholic acid was increased at 12 weeks compared to control within a subset of individuals (mean difference 16.2 ug/uL, p=0.022). No significant differences were observed between groups for stool SCFAs or microbial community structure.

Discussion: Dietary intake of rice bran + navy beans demonstrates beneficial modulation of host and gut microbial metabolism and represents a practical and affordable means of increasing adherence to national guidelines for CRC control and prevention in a high-risk population.

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大肠癌癌症高危人群对膳食米糠和海军豆补充的血浆、尿液和粪便代谢产物的反应
引言全谷物和豆类的饮食摄入和充足的体育活动(PA)与降低癌症(CRC)风险有关。实施了一项单盲、双臂、随机、安慰剂对照的试点试验,以评估米糠+海军豆补充和PA教育的12周饮食干预对CRC高危人群代谢产物谱和肠道微生物组的影响。方法将20名成年人按1:1随机分为饮食干预组或对照组。所有参与者在基线接受PA教育。16种研究食品是用热稳定米糠+海军蓝豆粉或Fibersol®-2作为安慰剂制备的。干预参与者每天食用30克米糠+30克海军蓝豆粉;对照组每天服用10g安慰剂。通过UPLC-MS/MS进行非靶向代谢产物分析,以评估0、6和12周时的血浆、尿液和粪便。还通过UPLC-MS/MS和16S扩增子测序的微生物群落结构分析了粪便中的初级和次级胆汁酸(BA)以及短链脂肪酸(SCFAs)。使用双向方差分析比较各组之间代谢物的差异,使用混合模型比较各组之间BA、SCFA以及微生物群落结构的α和β多样性测量的差异。结果与对照组相比,在整个生物基质中,干预导致几种氨基酸和脂质代谢产物发生变化。在12周时,血浆中的氨基酸S-甲基半胱氨酸的差异为2.33倍(p<0.001),尿液中的差异为3.33倍(p=0.008)。6周和12周后,血浆和尿液中4-甲氧基苯酚硫酸盐的倍数差异(p<0.001)是米糠和海军豆联合干预的一个新结果。在12周时,观察到脂质十八碳烯二酰肉碱的血浆差异为2.98倍(p=0.002),粪便差异为17.74倍(p=0.026)。对于粪便BA,在一组个体中,与对照组相比,3-氧代胆酸在12周时增加(平均差异16.2ug/uL,p=0.022)。在粪便SCFAs或微生物群落结构方面,各组之间没有观察到显著差异。讨论米糠+海军蓝豆的膳食摄入证明了对宿主和肠道微生物代谢的有益调节,并代表了在高危人群中提高对CRC控制和预防国家指南的遵守程度的一种实用且负担得起的方法。
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