Multi-omics Reveal the Enabling Factors of Aplastic Anaemia

Abstract

Background: Aplastic anemia is a kind of anemia caused by bone marrow failure due to autoimmune abnormalities. Numerous studies have shown that autoimmunity is regulated by intestinal microflora, and that most intestinal microflora regulates immunity through short chain fatty acids. At the same time, almost all patients with aplastic anemia will have bone marrow adipose tissue, and the process of bone marrow adipose tissue is regulated by medium and long chain fatty acids. Our previous studies have found that the intestinal flora of aplastic anemia patients is different from that of normal people. Therefore, this study aims to conduct a comprehensive detection of the intestinal flora and fatty acid metabolism in patients with aplastic anemia and to study their correlation.Methods: Fatty acid compositions in the peripheral plasma and bone marrow supernatants of 12 newly diagnosed aplastic anaemia patients and 10 normal controls were comprehensively analysed by CG-MS. Gene sequencing of faecal samples from both groups was also performed with macrogene sequencing technology.Results: Based on the metagenomic sequencing technology, we analyzed the difference of intestinal flora between group AA and group NC. We found that the main difference between the two groups existed in the bacterial community, and the abundance of most microbial species showed a downward trend. Based on the CG-MS lipid detection technique, we found that there were differences in lipid metabolism between the AA group and the NC group, whether short chain fatty acids or medium and long chain fatty acids. 8. The most attractive findings are interrelationships between the Citrobacter spp 、stearic acid (c18:0), isobutyric acid, and lysine degradation and betaine biosynthesis pathway and the interrelationship between catenibacterium_mitsuokai species at Catenibacterium, cis-7,10,13,16-docosatetraenoic acid (c22:4), ubiquinone and other terpenoid quinones pathway.We also found the intercorrelation between the abundance of Enhydrobacter genus and Enhydrobacter_aerosaccus species, cis-13,16-docosadienoic acid in peripheral plasma, cis-7,10,13,16-docosatetraenoic acid in bone marrow supernatant, tyrosine and tryptophan biosynthesis pathways.Conclusions: Our results show that Citrobacter infection may be a driving factor for aplastic anaemia, identifying a potential role for stearic acid in the immunopathogenesis of aplastic anaemia. Our study also demonstrates the potential role of 22-carbon long-chain polyunsaturated fatty acids, which may not only be involved in the metabolism of fibroblasts in bone marrow but also influence the formation of the bone marrow microenvironment, in aplastic anaemia.