Lower abundance of human gut virus species is associated with cancer cachexia

Abstract Cancer cachexia has been linked to gut bacterial alterations, but alterations of gut viruses, mostly bacteriophages, have not yet been explored. We performed shotgun metagenomic sequencing of DNA from stool samples of 78 cachectic and 42 non-cachectic cancer patients. K-mer-based matching to reference databases revealed abundance variations of bacteria and viruses. Beyond bacterial alterations, cachectic patients exhibited significantly lower bacteriophage abundance, predominantly affecting Caudovirales and Siphoviridae species (double-stranded DNA) but also Inoviridae and Microviridae families (single-stranded DNA). Machine learning models exploiting the data for classification between cachectic and non-cachectic state yielded an AUC of 0.704. Caudovirales and Siphoviridae species were among the top-most important classifiers. AUC increased to 0.850 with solely antibiotic-exposed samples from 20 cachectic and 10 non-cachectic patients. This study is the first to suggest a link between cancer cachexia and intestinal bacteriophage richness. This could constitute a new basis for hypothesis-driven research in cancer cachexia diagnosis and treatment.