Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
Gastroenterology. 2022 Oct;163(4):908-921. doi: 10.1053/j.gastro.2022.06.038. Epub 2022 Jun 18.
BACKGROUND & AIMS: The enteric mycobiota is a major component of the human gut microbiota, but its role in colorectal cancer (CRC) remains largely elusive. We conducted a meta-analysis to uncover the contribution of the fungal mycobiota to CRC.
We retrieved fecal metagenomic data sets from 7 previous publications and established an additional in-house cohort, totaling 1329 metagenomes (454 with CRC, 350 with adenoma, and 525 healthy individuals). Mycobiota composition and microbial interactions were analyzed. Candidate CRC-enriched fungal species (Aspergillus rambellii) was functionally validated in vitro and in vivo.
Multicohort analysis revealed that the enteric mycobiota was altered in CRC. We identified fungi that were associated with patients with CRC or adenoma from multiple cohorts. Signature CRC-associated fungi included 6 enriched (A rambellii, Cordyceps sp. RAO-2017, Erysiphe pulchra, Moniliophthora perniciosa, Sphaerulina musiva, and Phytophthora capsici) and 1 depleted species (A kawachii). Co-occurrent interactions among CRC-enriched fungi became stronger in CRC compared with adenoma and healthy individuals. Moreover, we reported the transkingdom 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 patients with CRC from healthy individuals (the area under the curve relative change increased by 1.44%-10.60%).
This study reveals enteric mycobiota signatures and pathogenic fungi in stages of colorectal tumorigenesis. Fecal fungi can be used, in addition to bacteria, for noninvasive diagnosis of patients with CRC.
肠共生真菌是人类肠道微生物群的主要组成部分，但它在结直肠癌（CRC）中的作用在很大程度上仍难以捉摸。我们进行了一项荟萃分析，以揭示真菌菌群对 CRC 的贡献。
我们从 7 篇先前的出版物中检索了粪便宏基因组数据集，并建立了一个额外的内部队列，共包含 1329 个宏基因组（454 例 CRC、350 例腺瘤和 525 例健康个体）。分析了真菌群落组成和微生物相互作用。在体外和体内验证了候选 CRC 富集真菌物种（aspergillus rambellii）的功能。
多队列分析显示，CRC 患者的肠共生真菌发生了改变。我们从多个队列中鉴定出与 CRC 或腺瘤患者相关的真菌。CRC 相关真菌的特征包括 6 种富集的真菌（aspergillus rambellii、cordyceps sp. RAO-2017、erysiphe pulchra、moniliophthora perniciosa、sphaerulina musiva 和 phytophthora capsici）和 1 种减少的真菌（aspergillus kawachii）。与腺瘤和健康个体相比，CRC 中与 CRC 相关的真菌之间的并发相互作用更强。此外，我们报告了肠共生真菌与 CRC 进展过程中细菌之间的跨物种相互作用，其中 aspergillus rambellii 与 CRC 相关细菌 fusobacterium nucleatum 密切相关。aspergillus rambellii 在体外促进 CRC 细胞生长和异种移植小鼠肿瘤生长。我们进一步发现，真菌和细菌的组合生物标志物比仅包含细菌的标志物更能准确地区分 CRC 患者和健康个体（曲线下面积相对变化增加 1.44%-10.60%）。
本研究揭示了结直肠癌发生过程中的肠共生真菌特征和致病真菌。除细菌外，粪便真菌也可用于非侵入性诊断 CRC 患者。
