Plasma Metabolomic and Intestinal Microbial Analyses of Patients With Severe Aplastic Anemia

Abstract

Aplastic anemia results from bone marrow failure caused by an autoimmune abnormality, but the pathogenesis of severe aplastic anemia (SAA) is not well characterized. To identify potential metabolic markers of SAA and to further elucidate the pathogenetic mechanisms of SAA, we performed a metabolomic study of plasma samples and characterized the intestinal microbiota of patients with SAA and healthy controls. Patients with SAA had more Enterobacteriales and Lactobacillales, but fewer Bacteroidales, Clostridiales, and Erysipelotrichales than healthy controls. At the species level, the abundances of Escherichia coli and others including Clostridium citroniae were higher, whereas those of Prevotella copri, Roseburia faecis, and Ruminococcus bromii were lower. Eight metabolites showed significantly different plasma concentrations in the SAA and healthy control groups. Coumaric acid, L-phenylalanine, and sulfate were present at higher concentrations in the SAA group; whereas L-glutamic γ-semialdehyde, theobromine, 3a, 7a-dihydroxy-5b-cholestane, γ-δ-dioxovaleric acid, and (12Z)-9, 10-dihydroxyoctadec-12-enoic acid were present at lower concentrations. In conclusion, patients with SAA show abnormalities in both their plasma metabolomes and intestinal microbial compositions. These differences might reflect the molecular mechanisms involved in the defective immunity that characterizes SAA.