于君团队：大肠癌中的肠道真菌群特征和促癌真菌
- ①纳入7项（共1329个粪便宏基因组）数据集进行荟萃分析，总结肠道真菌菌群与结直肠癌（CRC）的关系；
- ②与健康人和腺瘤患者相比，CRC患者肠道内Aspergillus rambellii等6种真菌丰度增加，Aspergillus kawachii丰度减少；
- ③体内和体外实验表明，A. rambellii可促进CRC细胞和异种移植小鼠肿瘤的生长；
- ④CRC患者肠道内真菌-真菌、真菌-细菌相互作用明显增强，且与CRC病程呈正相关；
- ⑤联合使用真菌与细菌的生物标志物可在临床上更准确地诊断CRC。
主编推荐语
真菌菌群是人类肠道菌群的主要组成部分，但其在结直肠癌 (CRC) 中的作用未知。香港中文大学于君团队近期在Gastroenterology发表研究，通过对454个CRC、350个腺瘤以及525个健康人粪便进行宏基因组分析，发现在结直肠肿瘤发生阶段，肠道中真菌菌群失调以及病原真菌Aspergillus rambellii富集。这项研究表明粪便真菌也可作为诊断CRC的生物标志物。
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Altered mycobiota signatures and enriched pathogenic Aspergillus rambellii are associated with colorectal cancer based on multi-cohort fecal metagenomic analyses
基于多队列粪便宏基因组分析，真菌菌群特征的改变以及病原曲霉菌Aspergillus rambellii的富集与结直肠癌有关
10.1053/j.gastro.2022.06.038
2022-06-17, Article
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Background & Aims: Enteric mycobiota is a major component of human gut microbiota, but its role in colorectal cancer (CRC) remains largely elusive. We conducted a meta-analysis to uncover the contribution of fungal mycobiota to CRC.
Methods: We retrieved fecal metagenomic datasets from 7 previous publications and established an additional in-house cohort, totaling 1,329 metagenomes (454 CRC, 350 adenoma and 525 healthy subjects). Analyses of mycobiota composition and microbial interactions were conducted. Candidate CRC-enriched fungal species (Aspergillus rambellii) was functionally validated in vitro and in vivo.
Results: Multi-cohort analysis revealed that the enteric mycobiota was altered in CRC. We identified fungi that were associated with CRC and adenoma patients from multiple cohorts. Signature CRC-associated fungi included 6 enriched (Aspergillus rambellii, Cordyceps sp. RAO-2017, Erysiphe pulchra, Moniliophthora perniciosa, Sphaerulina musiva, and Phytophthora capsici) and 1 depleted species (Aspergillus kawachii). Co-occurrent interactions among CRC-enriched fungi became stronger in CRC compared to adenoma and healthy subjects. Moreover, we reported the trans-kingdom interactions between enteric fungi and bacteria in CRC progression, of which A. rambellii was closely associated with CRC-enriched bacteria Fusobacterium nucleatum. A. rambellii promoted CRC cell growth in vitro and tumor growth in xenograft mice. We further identified that combined fungal and bacterial biomarkers were more accurate than panels with pure bacterial species to discriminate CRC patients from healthy subjects (AUC relative change increased by 1.44%-10.60%).
Conclusions: This study reveals enteric mycobiota signatures and pathogenic fungi in stages of colorectal tumorigenesis. Fecal fungi can be utilized, in addition to bacteria, for non-invasive diagnosis of CRC patients.
First Authors:
Yufeng Lin
Correspondence Authors:
Jun Yu
All Authors:
Yufeng Lin,Harry Cheuk Hay Lau,Yali Liu,Xing Kang,Yiwei Wang,Nick Lung-Ngai Ting,Thomas Ngai-Yeung Kwong,Jing Han,Weixin Liu,Changan Liu,Junjun She,Sunny Hei Wong,Joseph Jao-Yiu Sung,Jun Yu
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