Cachexia, prevalent in up to 80% of cancer patients, is linked to decreased survival. This study investigated the gut microbiome's role in lung cancer cachexia using shotgun metagenomics and plasma metabolomics of 31 patients. Cachectic patients exhibited distinct gut microbial composition, functional pathways, and plasma metabolites. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were depleted in cachexia patients, mirroring depleted gut microbiota pathways. *Prevotella copri* and *Lactobacillus gasseri* correlated with BCAA and 3-oxocholic acid levels, respectively, in non-cachectic patients. Lipopolysaccharide biosynthesis was enriched in cachectic patients. A machine learning model using gut microbial features predicted cachexia. The study highlights links between cachectic metabolism and specific gut microbes, suggesting potential therapeutic targets.

Yueqiong Ni, Zoltan Lohinai, Yoshitaro Heshiki, Balazs Dome, Judit Moldvay, Edit Dulka, Gabriella Galffy, Judit Berta, Glen J. Weiss, Morten O. A. Sommer, Gianni Panagiotou