The Role of Gut Microbiota in Thalassemia Treatment using Hydroxyurea: Friend or Foe?

Hydroxyurea (HU), a fetal hemoglobin inducer, effectively alleviates symptoms in beta-thalassemia patients; however, its efficacy varies among individuals, potentially due to differences in hydroxyurea metabolism and composition of the gut microbiota. Previous studies have indicated that these factors can influence drug and disease metabolism, including that of thalassemia. This study aimed to establish a link between the gut microbiota and hydroxyurea response in beta-thalassemia major patients. Stool samples were collected from 45 beta-thalassemia patients and classified into three groups: responders, non-responders, and those not using hydroxyurea. Sequencing was performed on the V3-V4 hyper-variable region of the 16SrRNA gene. The analysis uncovered noteworthy distinctions in the gut microbiota among the three groups at both the genus and species levels. The response to hydroxyurea was associated with butyrate-producing bacteria from the phylum Firmicutes. Responders exhibited an enrichment in butyrate-producing bacteria such as Faecalibacterium, Butyrivibrio, Oscillobacter, Gemmiger, and Eubacterium. Non-responders, on the other hand, had higher levels of Prevotella, Mitsuokella, and Treponema. Non-users were characterized by an abundance of Succinivibrio, followed by Bacteroides and Megasphaera. These findings suggest that altered gut microbiota may contribute to inter-individual variation in hydroxyurea response, highlighting specific microbes that could potentially serve as biomarkers for thalassemia or predict hydroxyurea efficacy.