Samuele Roncareggi, Francesca Fioredda, Katia Girardi, Simone Serrao, Giulia Capitoli, Rebecca Fumagalli, Marta Nobile, Grazia Fazio, Fabiola Guerra, Maria Grazia Valsecchi, Stefano Rebellato, Marika Casillo, Maria Rosaria Fantuz, Giovanni Savarese, Giuseppe Paglia, Eleonora Gambineri, Adriana Balduzzi, Andrea Biondi, Francesco Saettini
GATA2 deficiency predisposes patients to recurrent infections, myelodysplastic neoplasms (MDSs), and malignancies through disrupted hematopoiesis and immune dysfunction. The role of the gut microbiome (GM) in this condition remains poorly defined. In this multicenter study, we analyzed GM composition, metabolomic, and lipidomic profiles in 12 Italian GATA2-deficient patients, comparing non-HSCT and post-HSCT GATA2-deficient individuals with healthy controls. Non-HSCT patients showed a relative enrichment of Proteobacteria-associated Gram-negative taxa, accompanied by increased levels of metabolites and lipids previously associated with inflammatory processes. Post-HSCT patients displayed profiles with a trend toward partial normalization of GM composition and metabolic features. Overall, our findings suggest the presence of microbiome and metabolic patterns in GATA2-deficient patients, which may reflect underlying immune and hematopoietic alterations, although these observations should be interpreted as descriptive and require validation in larger cohorts.