Methanobrevibacter smithii associates with colorectal cancer through trophic control of the cancer bacteriome (LC-MS data)

The human gut is colonized by trillions of microbes that influence the health of their human host. Whereas many bacterial species have now been linked to a variety of different diseases, the involvement of Archaea in human disease remains elusive. Here we searched for gut archaeal signatures of disease by screening 19 cross-sectional clinical studies comprising more than 1,800 individuals. We found that associations between Archaea and medical disorders are common but highly variable and are dominated by a significant increase of Methanobrevibacter smithii in colorectal cancer (CRC) patients. Metabolic modelling and in vitro co-culture identified distinct mutualistic interactions of M. smithii with CRC-causing bacteria such as Fusobacterium nucleatum, including metabolic enhancement. Metabolomics further revealed archaeal-derived compounds with tumor-modulating properties. This provides the first mechanistic link between human gut archaeome and CRC and highlights its role in modulating health in humans through trophic control of the resident bacteriome.人体肠道内定植着数以万亿计的微生物，这些微生物会对宿主的健康产生调控作用。尽管目前已有多种细菌被证实与多种不同疾病存在显著关联，但古菌（Archaea）在人类疾病中的参与机制仍尚不明确。本研究通过对涵盖1800余名受试者的19项横断面临床研究进行系统性筛查，旨在探寻与人类疾病相关的肠道古菌标志物。我们发现，古菌与各类医学病症之间存在关联的情况十分普遍，但关联模式具有高度异质性，其中结直肠癌（CRC）患者体内的史密斯甲烷短杆菌（Methanobrevibacter smithii）显著富集，这是最为突出的特征。代谢建模与体外（in vitro）共培养实验证实，史密斯甲烷短杆菌与结直肠癌相关致病菌（如具核梭杆菌（Fusobacterium nucleatum））之间存在独特的互利共生相互作用，且涉及代谢层面的增强效应。代谢组学分析进一步揭示了古菌来源的、具有肿瘤调节活性的化合物。本研究首次阐明了人类肠道古菌组与结直肠癌之间的机制性关联，并凸显了古菌通过营养调控宿主定植菌群，进而影响人类健康的关键作用。