The Association Between Gut Microbiome and Cachexia in Colorectal Cancer: A Systematic Review.

Background/Objectives: Colorectal cancer (CRC) is complicated by cachexia, a wasting syndrome with muscle and fat loss that worsens survival and treatment outcomes. Evidence suggests that the gut microbiome may contribute to CRC cachexia, but its role remains unclear. This systematic review synthesizes evidence to identify microbial signatures linked to cachexia hallmarks in CRC. Methods: The protocol was pre-registered with PROSPERO and followed PRISMA guidelines. PubMed, Web of Science, and Scopus were searched for studies on CRC patients and preclinical models with cachexia. Eligible studies compared microbiota composition between cachectic and non-cachectic groups to identify alterations linked to cachexia progression. Study quality was assessed using the Newcastle-Ottawa Scale and CAMARADES checklist. Results: Of 2456 records, 15 studies met inclusion criteria, including 13 preclinical studies and 2 clinical studies. Study quality was moderate for preclinical studies and high for clinical cohort studies. Murine CRC cachexia models showed reduced alpha diversity and beta diversity shifts. Butyrate-producing taxa were depleted, whereas Enterobacteriaceae and other pathobionts were enriched. Some microbial changes were independent of food intake and linked to inflammation, metabolic dysregulation, and muscle wasting. Clinical evidence was limited to two reports from the same cohort, in which higher pre-surgical abundance of Fusobacterium nucleatum and lower Porphyromonas and Actinomyces spp. were associated with cachexia onset. Conclusions: Current evidence suggests an association between CRC-associated cachexia and gut microbiome alterations, but causality, directionality, and clinical relevance remain uncertain.