Deferiprone has less benefits on gut microbiota and metabolites in high iron-diet induced iron overload thalassemic mice than in iron overload wild-type mice: A preclinical study

Aims: This study aimed to investigate the changes in gut microbiota in iron-overload thalassemia and the roles of an iron chelator on gut dysbiosis/inflammation, and metabolites, including short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO). Main methods: Adult male C57BL/6 mice both wild-type (WT: n = 15) and heterozygous beta-thalassemia (BKO: n = 15) were fed on either a normal (ND: n = 5/group) or a high-iron diet for four months (HFe: n = 10/group). HFe-treated WT and HFe-treated BKO groups were further subdivided into two subgroups and each subgroup given either vehicle (n = 5/subgroup) or deferiprone (n = 5/subgroup) during the last month. Gut microbiota profiles, gut barrier characteristics, levels of proinflammatory cytokines, and plasma SCFAs and TMAO were determined at the end of the study. Key findings: HFe-fed WT mice showed distinct gut microbiota profiles from those of ND-fed WT mice, whereas HFe-fed BKO mice showed slightly different gut microbiota profiles from ND-fed BKO. Gut inflammation and barrier disruption were found only in HFe-fed BKO mice, however, an increase in plasma TMAO levels and decreased levels of SCFAs were observed in both WT and BKO mice with HFe-feeding. Treatment with deferiprone, gut dysbiosis and disturbance of metabolites were attenuated in HFe-fed WT mice, but not in HFe-fed BKO mice. Increased Verrucomicrobia and Ruminococcaceae were associated with the beneficial effects of deferiprone. Significance: Iron-overload leads to gut dysbiosis/inflammation and disturbance of metabolites, and deferiprone alleviates those conditions more effectively in WT than in those that are thalassemic.

Automated summary

This study investigated the changes in gut microbiota and metabolites in iron-overload thalassemia, as well as the effect of an iron chelator on gut dysbiosis and inflammation. The results showed that iron-overload led to gut dysbiosis, inflammation, and disturbance of metabolites, and treatment with the iron chelator deferiprone alleviated these conditions more effectively in wild-type mice than in thalassemic mice. The study suggests that deferiprone may be a potential therapeutic drug for iron-related gut diseases.