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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.<\/jats:p>","DOI":"10.1038\/s41396-021-00998-8","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T13:03:25Z","timestamp":1621256605000},"page":"3207-3220","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-7354","authenticated-orcid":false,"given":"Yueqiong","family":"Ni","sequence":"first","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology\u2014Hans Kn\u00f6ll Institute , 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June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Dr. Weiss reports personal fees and ownership interest from Circulogene, personal fees from Paradigm, personal fees from Angiex, personal fees and ownership interest from Exact Sciences, personal fees from Genomic Health, personal fees from GLG Council, travel and lodging fees from Tesaro, personal fees and ownership interest from MiRanostics Consulting, personal fees from Guidepoint Global, personal fees from Imaging Endpoints II, personal fees from Spring Bank Pharmaceuticals, personal fees from IBEX Medical Analytics, travel and lodging fees from GlaxoSmithKline, personal fees from SOTIO US, and personal fees from Gossamer Bio, outside the submitted work. In addition, Dr. Weiss is a former employee and stockholder of Unum Therapeutics, an employee of SOTIO US, and has a patent PCT\/US2011\/020612 issued. All other authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}