背景:大多数散发性结直肠癌(CRC)通过腺瘤-癌序列发展。虽然肠道菌群失调有助于CRC的发病机制,与结直肠腺瘤-癌序列密切相关的精确微生物类群仍然难以捉摸。本Meta分析旨在总结AD和CRC患者肠道菌群特征。
方法:PubMed,Embase,科克伦图书馆,和WebofScience进行了病例对照研究,比较了AD患者粪便中肠道微生物群的相对丰度,CRC,和健康对照(HC)从开始到2024年1月。使用具有95%置信区间(CI)的加权平均差(WMD)来显示结果。纽卡斯尔-渥太华量表(NOS)用于评估相关文献的质量。使用Egger和Begg的测试评估了出版偏差。
结果:纳入了11项研究,涉及477例CRC患者,628例AD患者,和864个健康对照。与HC相比,AD患者的Chao1指数显着降低(WMD=-30.17,95%CI[-41.10,-19.23],P<0.001)和香农指数(WMD=-0.1195%CI[-0.18,-0.04],P=0.002)。与AD相比,CRC患者的Chao1指数明显较高(WMD=22.09,95%CI[7.59,36.00],P=0.003)和香农指数(WMD=0.08,95%CI[0.00,0.15],P=0.037)。肠杆菌科(WMD=0.0395%CI[0.00,0.05],P=0.047;WMD=0.0295%CI[0.00,0.04],P=0.027)按对照-AD-CRC顺序显著增加,而布劳蒂亚(WMD=-0.0095%CI[-0.01,-0.00],P=0.001;WMD=-0.0095%CI[-0.00,-0.00],P=0.002)减少。与HC相比,变形杆菌的相对丰度(WMD=0.0595%CI[0.03,0.07],P<0.001),梭杆菌(WMD=0.0295%CI[0.00,0.03],P=0.042),链球菌科(WMD=0.0395%CI[0.01,0.05],P=0.017),Prevotellaceae(WMD=0.0295%CI[0.00,0.04],P=0.040),和大肠杆菌-志贺氏菌(WMD=0.0695%CI[0.01,0.11],P=0.021)在CRC组中富集。Alistipes的相对丰度(WMD=0.0095%CI[0.00,0.01],P=0.032)和链球菌(WMD=0.0095%CI[0.00,0.00],P=0.001)在AD与HC中增加。Firmicutes的相对丰度(WMD=-0.0795%CI[-0.12,-0.03],P=0.003),双歧杆菌(WMD=-0.0395%CI[-0.05,-0.01],P=0.016),和克雷伯菌(WMD=-0.0195%CI[-0.01,-0.00],P=0.001)在CRC和HC中降低。与AD相比,Firmicutes的相对丰度(WMD=-0.0495%CI[-0.07,-0.02],P=0.002),肽链球菌科(WMD=-0.0395%CI[-0.05,-0.00],P=0.021),落叶松科(WMD=-0.0495%CI[-0.08,-0.00],P=0.037),Ruminocycaceae(WMD=-0.0695%CI[-0.09,-0.03],P<0.001),粪杆菌(WMD=-0.0195%CI[-0.02,-0.01],P=0.001),和衣原体(WMD=-0.0295%CI[-0.03,-0.00],P=0.040)在CRC组中降低,而变形杆菌(WMD=0.0495%CI[0.02,0.05],P<0.001)增加。
结论:菌群失调的特征是产生短链脂肪酸(SCFA)的细菌水平降低,减少抗炎细菌,促炎细菌增加,并且具有细胞毒性作用的细菌对DNA的破坏可能代表结直肠腺瘤/癌的特定微生物特征。需要进一步的研究来阐明肠道菌群失调导致从AD到CRC进展的机制,并探索特定微生物群标志物在临床治疗和非侵入性筛查中的潜力。
BACKGROUND: Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC\'s pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC.
METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95 % confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger\'s and Begg\'s tests.
RESULTS: Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD = -30.17, 95 % CI [-41.10, -19.23], P < 0.001) and Shannon index (WMD = -0.11 95 % CI [-0.18, -0.04], P = 0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD = 22.09, 95 % CI [7.59, 36.00], P = 0.003) and Shannon index (WMD = 0.08, 95 % CI [0.00, 0.15], P = 0.037). Enterobacteriaceae (WMD = 0.03 95 % CI [0.00,0.05], P = 0.047; WMD = 0.02 95 % CI [0.00,0.04], P = 0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD = -0.00 95 % CI [-0.01, -0.00], P = 0.001; WMD = -0.00 95 % CI [-0.00, -0.00], P = 0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD = 0.05 95 % CI [0.03,0.07], P < 0.001), Fusobacteria (WMD = 0.02 95 % CI [0.00,0.03], P = 0.042), Streptococcaceae (WMD = 0.03 95 % CI [0.01,0.05], P = 0.017), Prevotellaceae (WMD = 0.02 95 % CI [0.00,0.04], P = 0.040), and Escherichia-Shigella (WMD = 0.06 95 % CI [0.01, 0.11], P = 0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD = 0.00 95 % CI [0.00,0.01], P = 0.032) and Streptococcus (WMD = 0.00 95 % CI [0.00,0.00], P = 0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD = -0.07 95 % CI [-0.12, -0.03], P = 0.003), Bifidobacteria (WMD = -0.03 95 % CI [-0.05, -0.01], P = 0.016), and Klebsiella (WMD = -0.01 95 % CI [-0.01, -0.00], P = 0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD = -0.04 95 % CI [-0.07, -0.02], P = 0.002), Peptostreptococcaceae (WMD = -0.03 95 % CI [-0.05, -0.00], P = 0.021), Lachnospiraceae (WMD = -0.04 95 % CI [-0.08,-0.00], P = 0.037), Ruminococcaceae (WMD = -0.06 95 % CI [-0.09,-0.03], P < 0.001), Faecalibacterium (WMD = -0.01 95 % CI [-0.02, -0.01], P = 0.001), and Lachnoclostridium (WMD = -0.02 95 % CI [-0.03, -0.00], P = 0.040) was decreased in the CRC group, while Proteobacteria (WMD = 0.04 95 % CI [0.02,0.05], P < 0.001) was increased.
CONCLUSIONS: The dysbiosis characterized by reduced levels of short-chain fatty acid (SCFA)-producing bacteria, decreased anti-inflammatory bacteria, increased pro-inflammatory bacteria, and an elevation of bacteria with cytotoxic effects damaging to DNA may represent the specific microbial signature of colorectal adenoma/carcinoma. Further research is required to elucidate the mechanisms by which gut dysbiosis leads to the progression from AD to CRC and to explore the potential of specific microbiota markers in clinical treatment and non-invasive screening.