Integrated metabolomic and microbiome analysis identifies Cupriavidus metallidurans as a potential therapeutic target for β-thalassemia.

Abstract

β-thalassemia(β-TH) is an inherited hemoglobin disorder marked by ineffective erythropoiesis, anemia, splenomegaly, and systemic iron overload, predominantly affecting developing countries in tropical and subtropical regions. Despite extensive research on its pathogenesis, the interactions between gut microbiota and metabolites in β-TH remain poorly understood. This study compares fecal metabolomics and metagenomics between wildtype (Wt) and heterozygous Th3/+ mice, a model for non-transfusion-dependent β-thalassemia intermedia. Our results show increased intestinal bilirubin metabolism, with significant elevations in metabolites such as biliverdin, bilirubin, and stercobilin. Metagenomic analysis revealed notable differences in bacterial composition between Th3/+ and Wt mice. Specifically, Cupriavidus metallidurans was identified as a key bacterium that mitigates anemia by reducing liver and spleen iron deposition. This is the first study to ameliorate anemia in mice by altering gut microbiota, presenting new strategies for β-TH management.