Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

恶病质与癌症患者的生存率降低有关，患病率高达 80%。恶病质的病因知之甚少，治疗选择有限。在这里，我们通过整合 31 名肺癌患者的鸟枪法宏基因组学和血浆代谢组学研究人类肠道微生物组在恶病质中的作用。与非恶病质患者相比，恶病质组在肠道微生物组成、宏基因组功能通路和相关血浆代谢物方面表现出显着差异。恶病质患者血浆中的支链氨基酸 (BCAA)、甲基组胺和维生素显着耗竭，这也反映在相关肠道微生物群功能途径的耗竭上。分别为普氏菌和加氏乳杆菌。此外，恶病质患者的肠道微生物群脂多糖生物合成能力显着富集。在仅使用肠道微生物特征的高性能机器学习模型中进一步观察到肠道微生物组参与恶病质。我们的研究证明了恶病质宿主代谢与临床环境中特定肠道微生物种类和功能之间的联系，表明肠道微生物群可能对恶病质产生影响，并具有可能的治疗应用。