Table_2_Virulent Bacteria as Inflammatory and Immune Co-Factor in Colon Carcinogenesis: Evidence From Two Monozygotic Patients and Validation in CRC Patient and Healthy Cohorts.xlsx

Colorectal carcinoma (CRC) is a common disease, the incidence of which is increasing according to Western lifestyle; it remains to have a poor prognosis. Western nutriments are presumed to induce mild inflammation within the colonic mucosa, resulting in the accumulation of DNA alterations in colonocytes through a multistage carcinogenesis process. This suggests that most CRCs are related to the environment. Of interest, fecal microbiota composition has been shown yielding a novel approach regarding how environment changes may impact health and disease. Here, we compare whole shotgun metagenomic gut microbiota of two monozygotic twin sisters, one of whom is suffering from an advance colorectal tumor with a profound disequilibrium of the composition of the gut microbiota due to the overexpression of virulent bacteria such as E. coli, Shigella, and Clostridium species in the colon cancer patient’s feces contrasting with low levels of bacterial species such as Faecalibacterium and Akkermansia usually enriched in the healthy adults’ microbial flora. The disequilibrium in microbiota of the CRC patient’s feces as compared to her monozygotic twin sister is linked to inflammatory and immune cell infiltrates in the patient’s colonic tissue. We speculate on the role of microbiota disequilibrium on the immune-tolerant cell infiltrate within CRCs.

结直肠癌（Colorectal carcinoma, CRC）是一种常见恶性疾病，其发病率随西方生活方式的流行呈逐年上升趋势，且整体预后仍不容乐观。西方膳食中的营养成分被认为可诱导结肠黏膜产生轻度炎症，进而通过多阶段癌变进程，导致结肠上皮细胞内DNA突变积累。这提示绝大多数结直肠癌的发生与环境因素密切相关。值得关注的是，粪便菌群组成的相关研究已为解析环境变化如何影响机体健康与疾病提供了全新的研究视角。本研究对两名同卵双胞胎姐妹的全鸟枪法宏基因组（shotgun metagenomic）肠道菌群进行了对比分析：其中一名受试者罹患进展期结直肠肿瘤，其粪便样本中大肠杆菌（E. coli）、志贺氏菌（Shigella）及梭菌属（Clostridium）等致病菌过度增殖，致使肠道菌群组成出现严重失衡；而其健康的同卵双胞胎姐妹的粪便样本中，粪杆菌属（Faecalibacterium）、嗜黏蛋白阿克曼菌（Akkermansia）等通常在健康成人肠道菌群中富集的细菌丰度则处于较低水平。相较于其健康的同卵双胞胎姐妹，结直肠癌患者粪便中的菌群失衡与其结肠组织内的炎症细胞及免疫细胞浸润密切相关。本研究就肠道菌群失衡在结直肠癌免疫耐受细胞浸润过程中所发挥的潜在作用展开了推测与探讨。