Association of Gut Microbiome Dynamics With Systemic Inflammation and Disease-Free Survival in Osteosarcoma Patients.
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Gut microbiota (GM) is increasingly recognised as a key modulator of cancer development, progression, and treatment response. However, clinical studies remain limited, especially in osteosarcoma (OS), the most common bone cancer in children and adolescents. In this study, we analysed GM diversity, composition, and predicted function in a small OS cohort (n = 18) using 16S rRNA gene sequencing of stool samples collected at diagnosis, during chemotherapy, and post-treatment. Microbial profiles were compared to healthy controls. Alpha diversity was assessed via ASVs, Shannon, inverse Simpson, and Faith's index; beta diversity via Bray-Curtis and UniFrac distances. We examined associations between GM profiles and clinical variables (age, gender, BMI, tumour volume, outcome) and systemic inflammation (e.g., C-reactive protein, CRP) using PERMANOVA, LEfSe, and Kaplan-Meier analysis. At diagnosis, OS patients showed reduced diversity and a distinct GM signature-depletion of anti-inflammatory genera (Blautia, Faecalibacterium, Roseburia) and enrichment of potentially pro-tumorigenic taxa (Collinsella, Streptococcus), which correlated with elevated CRP. Baseline GM composition stratified patients by long-term outcome, with specific taxa and predicted pathways linked to event-free survival. Chemotherapy induced transient dysbiosis, notably affecting Lactobacillus and Enterococcus, with partial recovery post-treatment. This is the first study to track GM alterations in OS patients across the disease course, extending current knowledge beyond preclinical models. As one of the few longitudinal microbiota studies in oncology, it highlights GM's potential as a biomarker, shedding light on the mechanisms underlying OS pathogenesis, though findings require validation in larger cohorts.