Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia

Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders.Here,we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia(ITP)patients and 52 healthy controls.Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally,and classifier based on species markers distinguished individuals with ITP from healthy controls.In particular,the abundance of Ruminococcus gnavus,Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-na?ve ITP patients,and the alterations of microbial species were correlated with clinical indices.Functionally,the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP,which may contribute to the onset of ITP by affecting the immune system.Furthermore,we found that corticosteroid treatment affected the gut microbiome of ITP.Compared with corticosteroid-sensitive ITP patients,we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome,which was different from that of the treatment-na?ve ITP patients.Together,we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.

Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization

This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colon of GVHD mice, we found that the number of F4/80+iNOS+ cells as well as the expression intensity of TNF-α and IL-1β was greater in the GVHD group than in the BM group, whereas the number of F4/80+CD206+ cells and the expression intensity of IL-10 and TGF-β was greater in the BM group than in the GVHD group. We investigated the effect of ATO on GVHD mice, and found that ATO treatment clearly improved the survival of the mice and reduced the severity of GVHD. In addition, ATO reduced the number of F4/80+iNOS+ cells, and increased the number of F4/80+CD206+ cells in the colon of GVHD mice. Furthermore, ATO sharply decreased CD86 and CD80 expression, and increased CD163 and CD206 expression in macrophages induced from aGVHD patients. Therefore,ATO can modulate the M1 and M2 phenotype in GVHD mice or in macrophages from aGVHD patients. Our data suggest that macrophage polarization is involved in the pathogenesis of aGVHD, and ATO treatment modulates macrophage polarization toward an M2 phenotype.