Multi-cohort analysis reveals altered archaea in colorectal cancer fecal samples across populations

IF 25.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology Pub Date : 2024-10-28 DOI:10.1053/j.gastro.2024.10.023

Tianhui Li, Olabisi Oluwabukola Coker, Yang Sun, Shiyu Li, Chuanfa Liu, Yufeng Lin, Sunny H. Wong, Yinglei Miao, Joseph JY. Sung, Jun Yu

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引用次数: 0

Abstract

Background and aim

Archaea are important components of the host microbiome, but their roles in colorectal cancer (CRC) remain largely unclear. We aimed to elucidate the contribution of gut archaea to CRC across multiple populations.

Methods

This study incorporated fecal metagenomic data from 10 independent cohorts from 7 countries and an additional in-house cohort, totaling 2101 metagenomes (748 CRC, 471 adenoma, and 882 healthy controls (HC)). Taxonomic profiling was performed using Kraken2 against the Genome Taxonomy Database. Alterations of archaeal communities and their interactions with bacteria and methanogenic functions were analyzed. Random Forest model was used to identify multicohort diagnostic microbial biomarkers in CRC.

Results

The overall archaeal alpha diversity shifted from HC, adenoma patients to CRC patients with Methanobacteriota phylum enriched while order Methanomassiliicoccales depleted. At the species level, Methanobrevibacter_A smithii and Methanobrevibacter_A sp002496065 were enriched, while 8 species, including Methanosphaera stadtmanae and Methanomassiliicoccus_A intestinalis, were depleted in CRC patients across multiple cohorts. Among them, M. stadmanae, Methanobrevibacter_A sp900314695 and Methanocorpusculum sp001940805 exhibited a progressive decrease in the HC-adenoma-CRC sequence. CRC-depleted methanogenic archaea exhibited enhanced co-occurring interactions with butyrate-producing bacteria. Consistently, methanogenesis-related genes and pathways were enriched in CRC patients. A model incorporating archaeal and bacterial biomarkers outperformed single-kingdom models in discriminating CRC patients from healthy individuals with AUC ranging from 0.744 to 0.931 in leave-one-cohort-out analysis.

Conclusions

This multicohort analysis uncovered significant alterations in gut archaea and their interactions with bacteria in healthy individuals, adenoma patients and CRC patients. Archaeal biomarkers, combined with bacterial features, have potential as non-invasive diagnostic biomarkers for CRC.

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多队列分析显示不同人群结直肠癌粪便样本中的古细菌发生了变化

背景和目的古细菌是宿主微生物组的重要组成部分，但它们在结直肠癌（CRC）中的作用在很大程度上仍不清楚。本研究纳入了来自 7 个国家的 10 个独立队列和一个额外的内部队列的粪便元基因组数据，共计 2101 个元基因组（748 个 CRC、471 个腺瘤和 882 个健康对照（HC））。使用 Kraken2 对基因组分类数据库进行了分类分析。分析了古细菌群落的变化及其与细菌和甲烷功能的相互作用。结果从HC、腺瘤患者到CRC患者的总体古细菌α多样性发生了变化，其中甲烷杆菌门富集，而甲烷纤毛虫目枯竭。在物种水平上，Methanobrevibacter_A smithii和Methanobrevibacter_A sp002496065在多个队列的CRC患者中富集，而包括Methanosphaera stadtmanae和Methanomassiliicoccus_A intestinalis在内的8个物种在CRC患者中枯竭。其中，M. stadmanae、Methanobrevibacter_A sp900314695和Methanocorpusculum sp001940805在HC-腺瘤-CRC序列中表现出逐渐减少的趋势。去除了 CRC 的产甲烷古菌与产丁酸菌的共生相互作用增强。一致的是，甲烷生成相关基因和通路在 CRC 患者中富集。结论这项多队列分析发现了健康人、腺瘤患者和 CRC 患者肠道古菌及其与细菌相互作用的显著变化。古菌生物标志物与细菌特征相结合，有望成为 CRC 的非侵入性诊断生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastroenterology 医学-胃肠肝病学

CiteScore

45.60

自引率

2.40%

发文量

4366

审稿时长

26 days

期刊介绍： Gastroenterology is the most prominent journal in the field of gastrointestinal disease. It is the flagship journal of the American Gastroenterological Association and delivers authoritative coverage of clinical, translational, and basic studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. Some regular features of Gastroenterology include original research studies by leading authorities, comprehensive reviews and perspectives on important topics in adult and pediatric gastroenterology and hepatology. The journal also includes features such as editorials, correspondence, and commentaries, as well as special sections like "Mentoring, Education and Training Corner," "Diversity, Equity and Inclusion in GI," "Gastro Digest," "Gastro Curbside Consult," and "Gastro Grand Rounds." Gastroenterology also provides digital media materials such as videos and "GI Rapid Reel" animations. It is abstracted and indexed in various databases including Scopus, Biological Abstracts, Current Contents, Embase, Nutrition Abstracts, Chemical Abstracts, Current Awareness in Biological Sciences, PubMed/Medline, and the Science Citation Index.