Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome

Giovanna Barbosa  Correia Riello; Priscila  Mendonça da Silva; Francisca Andrea  da Silva Oliveira; Roberta Taiane  Germano de Oliveira; Francisco Eliclecio  Rodrigues da Silva; Ivo Gabriel da  Frota França; Fábio  Miyajima; Vânia Maria Maciel Melo; Ronald Feitosa Pinheiro; Danielle S. Macedo

doi:10.18502/ijhoscr.v18i2.15377

Giovanna Barbosa Correia Riello Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Ceara, Fortaleza, CE, Brazil
Priscila Mendonça da Silva University Hospital Walter Cantidio, Federal University of Ceara, Brazil Brazilian Company of Hospital Services (EBSERH), Fortaleza, Ceará, Brazil
Francisca Andrea da Silva Oliveira Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
Roberta Taiane Germano de Oliveira Cancer Cytogenomic Laboratory, Drug Research and Development Center, Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil
Francisco Eliclecio Rodrigues da Silva Laboratory of Neuropsychopharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
Ivo Gabriel da Frota França Cancer Cytogenomic Laboratory, Drug Research and Development Center, Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil
Fábio Miyajima Oswaldo Cruz Foundation (Fiocruz), Branch Ceara, Eusebio, Brazil
Vânia Maria Maciel Melo Laboratory of Microbial Ecology and Biotechnology, Department of Biology, Federal University of Ceará, Fortaleza, Brazil
Ronald Feitosa Pinheiro Cancer Cytogenomic Laboratory, Drug Research and Development Center, Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil
Danielle S. Macedo Laboratory of Neuropsychopharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil

DOI: https://doi.org/10.18502/ijhoscr.v18i2.15377

Keywords: Gut microbiota composition; Myelodysplastic Syndromes; 16S rRNA gene; Highrisk MDS; Elderly people

Abstract

The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.