Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão

Abstract

The Myelodysplastic Syndromes (MDS) are a heterogeneous group of clonal diseases of hematopoietic progenitor cells characterized by cytopenias and dysplasias due to ineffective hematopoiesis and being considered a neoplasm due to the tendency to expand abnormal clones and may develop into acute myelogenous leukemia (AML). According to the World Health Organization, MDS is divided into categories such as refractory anemia (RA), refractory anemia with sideroblasts (RASA), refractory cytopenia with multilinear dysplasia (RCMD), and refractory anemia with excess blasts (RAEB), the latter being the most serious type of MDS. Covering the evolution of the disease and survival rates, the International Prognostic Classification System (IPSS) ranks very low (survival 8.8 years), low (survival 5.3 years), intermediate (survival 3 years), high (survival 1.6 years) and very high (survival 0.8 years). To date, no relationship has been made between changes in the intestinal microbiota in patients with MDS, although recent evidence has pointed to an important role of the gut microbiota in hematopoiesis. The present study aimed to analyze the microbiota profile of patients with SMD searching for possible clinical associations, as well to evaluate a possible interference of depression symptoms in the composition of this microbiota. In order to do so, the 16S rRNA gene was sequenced from the extraction of DNA directly from fecal samples from 30 MDS patients and 16 healthy elderly controls. The diversity and richness of the intestinal microbiota was evaluated by the Shannon, Simpson and Chao1 indices, and the contribution of other variables (subtypes of MDS, karyotype, blood count, IPSS, use of EPREX, transfusional dependence, body fat, styling, smoking and depression) was obtained by multivariate analysis. Psychological symptoms were assessed through the BECK depression scale. From the analysis of the sequencing, in relation to the phyla, it was observed a reduction of the phylum Actinobacteria in patients of subtype AREB (p = 0.063); for the filo Tenericutes, it was observed a decrease in the abundance of this phylum in the alcoholic patients (p = 0.010). As regards genera, a significant reduction in the abundance of the genus Ruminococcus spp. AREB subtype patients (p = 0.054) and with depressive symptoms (p = 0.022); the reduction of the genus Akkermansia spp. was found in SMD patients (p = 0.009), mainly in the high IPSS (p = 0.035); while the genus Prevotella spp. (p = 0.019) was increasedin this group and reduced in patients undergoing EPREX therapy (p = 0.008). In addition, the case of a 49-year-old patient with MDS and Bloom's syndrome was studied separately in the microbiota sequencing. It was observed the predominance of the phylum Verrucomicrobia (genus Akkermansia spp.) That was associated with the use of antibiotics the presence of colorectal adenoma and the malnutrition, characteristic of Bloom's syndrome. In conclusion, the findings of the present study show an important correlation between changes in the gut microbiota and clinical subtypes of high-risk MDS, with an inverse correlation between high-risk MDS and the genera Akkermansia spp. and Ruminococcus spp.. In addition to finding a strong association between the presence of depression syndromes and the significant reduction of the genus Ruminococcus spp ..