卷烟吸食和肠道微生物菌群在结直肠癌发生中起着重要作用。我们探讨了吸烟与结直肠癌（CRC）风险之间是否受到肠道菌群进入型的影响，并研究了吸烟相关进入型如何促进结直肠癌发生。进行了一项病例对照研究。通过16S rDNA测序确定了粪便微生物菌群。通过肠道菌群进入型对结直肠癌或腺瘤进行了亚分类。使用多元分析测试吸烟与结直肠肿瘤亚型发病几率的相关性。使用Mann-Whitney U检验找出亚型之间的差异微生物属、基因和通路。研究对象包括130例结直肠癌患者（I类型：n=77；II类型：n=53），120例腺瘤患者（I类型：n=66；II类型：n=54），以及130名健康参与者。吸烟显著增加了II型肿瘤的几率（所有趋势p<0.05），但对I型肿瘤无显著影响。吸烟与增加结直肠肿瘤的几率的关联性，在肠道菌群进入型方面存在显著差异（杂质性p<0.05）。在II型肿瘤中，致病性细菌（属Escherichia shigella）增加，益生菌（科Lachnospiraceae和Ruminococcaceae）减少，可能通过上调致癌信号通路、炎症/氧化应激反应通路以及蛋白磷脂酶D1/2、细胞色素C和前列腺素内过氧化物合成酶2表达，推动疾病进展。吸烟与II型结直肠肿瘤的几率增加相关，但与I型肿瘤无关，这支持了肠道菌群在吸烟和结直肠肿瘤之间的关联中可能发挥的潜在作用。© 2023 Cai J.A. et al.

Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis.A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes.Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend <0.05) but not for type I tumors. The associations of smoking with increased odds of colorectal neoplasm significantly differed by gut microbiota enterotypes (p<0.05 for heterogeneity). An increase in carcinogenic bacteria (genus Escherichia shigella) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression.Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms.© 2023 Cai J.A. et al.