背景:饮食摄入影响肠道微生物组组成,这反过来可能与结直肠癌(CRC)有关。肠道微生物组与结直肠癌发生的关联可能是通过细菌调节的,代谢活性代谢物,包括三甲胺N-氧化物(TMAO)及其前体,胆碱,左旋肉碱,还有甜菜碱.
方法:研究循环TMAO及其前体与CRC风险的前瞻性关联。TMAO,胆碱,甜菜碱,和L-肉碱在来自761例CRC病例和1:1个体匹配对照的前瞻性前列腺的基线血清样本中测量,肺,结肠直肠,使用靶向完全定量液相色谱串联质谱面板的卵巢癌筛查试验队列。代谢物与CRC风险的前瞻性关联,使用多变量条件逻辑回归,被测量。还研究了先验选择的饮食暴露与四种代谢物的关联。
结果:TMAO及其前体与CRC总体风险无关,但TMAO和胆碱与远端CRC的高风险呈正相关(连续ORQ90与Q10[95%CI]=1.90[CI,1.24-2.92;p=.003]和1.26[1.17-1.36;p<.0001],分别)。相反,胆碱与直肠癌呈负相关(ORQ90vs.Q10[95%CI]=0.77[0.76-0.79;p<.001])。红肉,先前与前列腺癌的CRC风险相关,肺,结肠直肠,卵巢癌筛查试验队列,与TMAO呈正相关(Spearmanrho=0.10;p=.0003)。
结论:血清TMAO和胆碱可能与较高的远端CRC风险相关,红肉可能与血清TMAO呈正相关。这些发现提供了对CRC病因学潜在的微生物介导机制的见解。
BACKGROUND: Dietary intake influences gut microbiome composition, which in turn may be associated with colorectal cancer (CRC). Associations of the gut microbiome with colorectal carcinogenesis may be mediated through bacterially regulated, metabolically active metabolites, including trimethylamine N-oxide (TMAO) and its precursors, choline, L-carnitine, and betaine.
METHODS: Prospective associations of circulating TMAO and its precursors with CRC risk were investigated. TMAO, choline, betaine, and L-carnitine were measured in baseline serum samples from 761 incident CRC cases and 1:1 individually matched controls in the prospective Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort using targeted fully quantitative liquid chromatography tandem mass spectrometry panels. Prospective associations of the metabolites with CRC risk, using multivariable conditional logistic regression, were measured. Associations of a priori-selected dietary exposures with the four metabolites were also investigated.
RESULTS: TMAO and its precursors were not associated with CRC risk overall, but TMAO and choline were positively associated with higher risk for distal CRC (continuous ORQ90 vs. Q10 [95% CI] = 1.90 [CI, 1.24-2.92; p = .003] and 1.26 [1.17-1.36; p < .0001], respectively). Conversely, choline was inversely associated with rectal cancer (ORQ90 vs. Q10 [95% CI] = 0.77 [0.76-0.79; p < .001]). Red meat, which was previously associated with CRC risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort , was positively associated with TMAO (Spearman rho = 0.10; p = .0003).
CONCLUSIONS: Serum TMAO and choline may be associated with higher risk of distal CRC, and red meat may be positively associated with serum TMAO. These findings provide insight into a potential microbially mediated mechanism underlying CRC etiology.