The human microbiota in cancer: unraveling microbial roles in hematological malignancies and colorectal cancer

The human microbiota plays a crucial role in modulating both health and disease, influencing immune responses, metabolism, and overall homeostasis. In recent years, its involvement in onco-hematological diseases has gained increasing attention. This thesis explores the dynamic interplay between the gut microbiome (GM) and the progression of cancer, with a specific focus on colorectal cancer (CRC) and hematological malignancies. Four studies are presented: The first study investigates the Wnt/β-catenin and PI3K/mTOR signaling pathways in APC-driven colorectal carcinogenesis, highlighting the potential role of specific microbiota compositions in modulating these pathways. The second study assesses how the GM affects the outcome of lymphoma patients treated with checkpoint inhibitors, identifying microbial signatures that could predict treatment response. The third study examines the impact of GM diversity on hematological recovery in patients with acute myeloid leukemia (AML) following induction therapy. Finally, the fourth study provides a comprehensive shotgun metagenomic analysis of the GM in pediatric recipients of allo HSCT, identifying microbial signatures associated with clinical outcomes and post-transplant recovery. Together, these studies underscore the importance of the microbiome in cancer progression and treatment outcomes, paving the way for microbiome-based diagnostic and therapeutic strategies in personalized medicine. The findings contribute to the growing body of evidence supporting the GM’s role as a critical modulator of carcinogenesis and therapeutic response, particularly in onco-hematological contexts.