Alterations of Gut Microbiota in Myelodysplastic Syndromes and Aplastic Anemia: Potential Relationship with Inflammatory Response

Background: Research shows that gut microbiota plays an important role in various blood diseases. Dysregulation of gut microbiota may lead to a chronic Th1 and/or Th17 cellular response stimulated by intestinal inflammatory responses, afterward Th17/Treg imbalance affects hematopoiesis through multiple signaling processes and ultimately mediates disease development. However, little is known about the gut microbiota distribution of patients with aplastic anemia (AA) and myelodysplastic syndromes (MDS), and its relation to the treatment response of AA. Although MDS and AA are both bone marrow failure diseases, their immune processes are quite different, which result in different manifestations.

Materials and Methods: Data were collected from a cohort of 27 newly diagnosed patients with AA, 17 newly diagnosed patients with MDS, and 15 gender- and age-matched normal controls. AA patients were classified as severe AA(SAA) and non-severe AA (NSAA), whereas MDS patients were classified as low-risk (LR-MDS) and high-risk (LR-MDS). Patients with SAA received anti-thymocyte globulin (ATG) + cyclosporine A (CsA), whereas those with NSAA received CsA only. Patients were evaluated for efficacy according to Camitta criteria after 6 months of treatment. Stool samples for the whole cohort at the time of diagnosis and AA patients at 6 months were collected and analyzed by 16S amplicon sequencing.

Results: No significant difference was found between AA and controls in microbiota abundance and colony structure(P>0.05). However, Collinsella, which is known to promote inflammatory response and increase intestinal permeability, increased in AA, while bacteria that maintain the balance of the gut microbiota, such as Ruminococcaceae and Faecalibacteriumm, decreased in AA. A significant difference in colony structure existed between SAA and NSAA (P=0.03). Proteobacteria and Collinsella were higher in NSAA. However, no correlation was found between the efficacy and the structure of gut microbiota(P＞0.05). A significant difference in colony structure was found between MDS and controls (P=0.002). An increase in Proteobacteria was found in MDS, suggesting a dysbiosis of the gut microbiota, along with an increase in Bacteroides, especially B. vulgatus, which could trigger immune responses as has been found in Crohn's disease. No difference was found between HR-MDS and LR-MDS (P＞0.05). A significant difference in colony structure was noticed between AA and MDS (P=0.035). MDS had increased Bacteroides, especially B.vulgatus, and decreased Coriobacteria, while AA had a relatively abundant Proteobacteria.

Conclusions: AA had an increased pro-inflammatory response and barrier disruption compared to normal controls and differed between SAA and NSAA, but did not correlate with treatment response. MDS had different gut microbiota from normal controls and AA, and possibly had a further increase in the mucosal immune response and disruption of the intestinal barrier. At the same time, pathogenic bacteria were more abundant in the gut microbiota of AA compared to MDS, which may be related to the lower neutrophil levels in AA patients. Topics: aplastic anemia, myelodysplastic syndromes, gut microbiota, efficacy, inflammatory response

No relevant conflicts of interest to declare.