The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Geriatrics, Hangzhou Red Cross Hospital, Hangzhou, China.
Microb Pathog. 2024 Oct;195:106889. doi: 10.1016/j.micpath.2024.106889. Epub 2024 Aug 26.
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.
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.
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.
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.
大多数散发性结直肠癌（CRC）是通过腺瘤-癌序列发展而来的。虽然肠道菌群失调有助于 CRC 的发病机制，但与结直肠腺瘤-癌序列密切相关的确切微生物类群仍难以捉摸。本荟萃分析旨在总结 AD 和 CRC 患者肠道菌群的特征。
从建库到 2024 年 1 月，通过 PubMed、Embase、Cochrane 图书馆和 Web of Science 搜索比较 AD、CRC 和健康对照（HC）患者粪便中肠道微生物群落相对丰度的病例对照研究。使用加权均数差（WMD）和 95%置信区间（CI）显示结果。使用纽卡斯尔-渥太华量表（NOS）评估纳入文献的质量。使用 Egger's 和 Begg's 检验评估发表偏倚。
纳入 11 项研究，涉及 477 例 CRC 患者、628 例 AD 患者和 864 例健康对照。与 HC 相比，AD 患者的 Chao1 指数明显降低（WMD=-30.17，95%CI[-41.10，-19.23]，P<0.001）和 Shannon 指数明显降低（WMD=-0.11，95%CI[-0.18，-0.04]，P=0.002）。与 AD 相比，CRC 患者的 Chao1 指数明显升高（WMD=22.09，95%CI[7.59，36.00]，P=0.003）和 Shannon 指数明显升高（WMD=0.08，95%CI[0.00，0.15]，P=0.037）。肠杆菌科（WMD=0.03，95%CI[0.00，0.05]，P=0.047；WMD=0.02，95%CI[0.00，0.04]，P=0.027）在控制-AD-CRC 顺序中显著增加，而 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）减少。与 HC 相比，厚壁菌门（WMD=0.05，95%CI[0.03，0.07]，P<0.001）、梭杆菌门（WMD=0.02，95%CI[0.00，0.03]，P=0.042）、链球菌科（WMD=0.03，95%CI[0.01，0.05]，P=0.017）、普雷沃氏菌科（WMD=0.02，95%CI[0.00，0.04]，P=0.040）和 Escherichia-Shigella（WMD=0.06，95%CI[0.01，0.11]，P=0.021）的相对丰度增加。Alistipes（WMD=0.00，95%CI[0.00，0.01]，P=0.032）和链球菌（WMD=0.00，95%CI[0.00，0.00]，P=0.001）的相对丰度在 AD 与 HC 中增加。厚壁菌门（WMD=-0.07，95%CI[-0.12，-0.03]，P=0.003）、双歧杆菌科（WMD=-0.03，95%CI[-0.05，-0.01]，P=0.016）和克雷伯氏菌（WMD=-0.01，95%CI[-0.01，-0.00]，P=0.001）的相对丰度在 CRC 与 HC 中降低。与 AD 相比，厚壁菌门（WMD=-0.04，95%CI[-0.07，-0.02]，P=0.002）、消化链球菌科（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）、瘤胃球菌科（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）和 Lachnoclostridium（WMD=-0.02，95%CI[-0.03，-0.00]，P=0.040）的相对丰度降低，而变形菌门（WMD=0.04，95%CI[0.02，0.05]，P<0.001）增加。
以短链脂肪酸（SCFA）产生菌水平降低、抗炎菌减少、促炎菌增加和具有损伤 DNA 作用的细胞毒性菌升高为特征的肠道菌群失调可能代表结直肠腺瘤/癌的特定微生物特征。需要进一步研究肠道菌群失调如何导致 AD 发展为 CRC，以及探索特定微生物标志物在临床治疗和非侵入性筛查中的潜在应用。
