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.