Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Ceará (UFC) |
Texto Completo: | http://www.repositorio.ufc.br/handle/riufc/43968 |
Resumo: | 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 .. |
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Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressãoGut microbiota profile of patients with myelodysplastic syndrome and its correlation with symptoms of depressionMicrobioma GastrointestinalSíndromes MielodisplásicasDepressãoThe 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 ..As Síndromes Mielodisplásicas (SMD) são um grupo heterogêneo de doenças clonais das células progenitoras hematopoiéticas caracterizadas por citopenias e displasias devido à hematopoiese ineficiente. A SMD é considerada uma neoplasia pela tendência à expansão de clones anormais podendo evoluir para leucemia mielóide aguda (LMA). De acordo com a Organização Mundial de Saúde, a SMD se divide em categorias como Anemia refratária (AR), Anemia refratária com sideroblastos em anéis (ARSA), Citopenia refratária com displasia multilinear (CRDM) e Anemia refratária com excesso de blastos (AREB), esta última sendo o tipo mais grave. De acordo coma evolução da doença e as taxas de sobrevida, o Sistema Internacional de Classificação de Prognóstico (IPSS) classifica em muito baixo (sobrevida de 8,8 anos), baixo (sobrevida de 5,3 anos), intermediário (sobrevida de 3 anos), alto (sobrevida de 1,6 anos) e muito alto (sobrevida de 0,8 anos). Até o presente momento, não foi feita nenhuma relação entre alterações na microbiota intestinal em pacientes com SMD, embora evidências recentes tenham apontado para um importante papel da microbiota intestinal na hematopoese. Neste contexto, o presente estudo visou analisar o perfil da microbiota de pacientes com SMD buscando possíveis associações clínicas, bem como avaliar uma possível interferência de sintomas de depressão na composição dessa microbiota. Para tanto, foi realizado o sequenciamento do gene 16S rRNA a partir da extração de DNA diretamente das amostras fecais de 30 pacientes com SMD e 16 controles idosos saudáveis. A diversidade e riqueza da microbiota intestinal foi avaliada pelos índices Shannon, Simpson e Chao1 e a contribuição de outras variáveis (subtipos de SMD, cariótipo, hemograma, IPSS, uso de alfaepoetina (EPREX®), dependência transfusional, gordura corporal, estilismo, fumo e depressão) foi obtida por análises multivariada. Os sintomas psicológicos foram avaliados por meio do inventário de depressão BECK.A partir das análises do sequenciamento, em relação aos filos, foi observado aumento do filo Actinobacteria nos pacientes de subtipo AREB (p=0.063), enquanto para o filo Tenericutes, foi observado diminuição da abundância deste filo nos pacientes etilistas (p=0.010). No que se refere aos gêneros, foi visto uma redução significativa da abundância do gênero Ruminococcus spp. nos pacientes de subtipo AREB (p=0.054) e com sintomas depressivos (p=0.022); a redução do gênero Akkermansia spp. foi encontrada nos pacientes SMD (p=0.009), principalmente nos de IPSS alto (p=0.035); enquanto que, o gênero Prevotella spp. mostrou-se aumentado significativamente nos pacientes com IPSS alto (p=0,019) e reduzido nos pacientes submetidos à terapia com EPREX® (p=0.008). Adicionalmente, foi estudado em separado o caso de uma paciente de 49 anos portadora de SMD e síndrome de Bloom.No sequenciamento da microbiota desta paciente, notou-se o predomínio do filo Verrucomicrobia (gênero Akkermansia spp.) que foi associado ao uso de antibióticos de forma rotineira, à presença de adenoma colorretal e ao quadro de desnutrição característico da síndrome de Bloom. Em conclusão, os achados do presente estudo mostram uma importante correlação entre alterações na microbiota intestinal e subtipos clínicos de SMD de alto risco, com destaque para uma correlação inversa entre SMD de alto risco e os gênerosAkkermansia spp. e Ruminococcus spp.Ademais, encontramos uma forte associação entre a presença de sintomas de depressão e a redução significativa do gênero Ruminococcus spp, bem como uma associação entre ogênero Prevotella sppe a terapia com EPREX®.Gaspar, Danielle MacedoCorreia, Giovanna Riello Barbosa2019-07-23T16:22:49Z2019-07-23T16:22:49Z2019-07-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfCORREIA, G. R. B. Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão. 2019. 135 f. Tese (Doutorado em Microbiologia Médica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019.http://www.repositorio.ufc.br/handle/riufc/43968porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2021-02-04T12:16:51Zoai:repositorio.ufc.br:riufc/43968Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:48:10.532534Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false |
dc.title.none.fl_str_mv |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão Gut microbiota profile of patients with myelodysplastic syndrome and its correlation with symptoms of depression |
title |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão |
spellingShingle |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão Correia, Giovanna Riello Barbosa Microbioma Gastrointestinal Síndromes Mielodisplásicas Depressão |
title_short |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão |
title_full |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão |
title_fullStr |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão |
title_full_unstemmed |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão |
title_sort |
Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão |
author |
Correia, Giovanna Riello Barbosa |
author_facet |
Correia, Giovanna Riello Barbosa |
author_role |
author |
dc.contributor.none.fl_str_mv |
Gaspar, Danielle Macedo |
dc.contributor.author.fl_str_mv |
Correia, Giovanna Riello Barbosa |
dc.subject.por.fl_str_mv |
Microbioma Gastrointestinal Síndromes Mielodisplásicas Depressão |
topic |
Microbioma Gastrointestinal Síndromes Mielodisplásicas Depressão |
description |
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 .. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-07-23T16:22:49Z 2019-07-23T16:22:49Z 2019-07-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
CORREIA, G. R. B. Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão. 2019. 135 f. Tese (Doutorado em Microbiologia Médica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019. http://www.repositorio.ufc.br/handle/riufc/43968 |
identifier_str_mv |
CORREIA, G. R. B. Perfil da microbiota intestinal de pacientes portadores da síndrome mielodisplásica e sua correlação com sintomas de depressão. 2019. 135 f. Tese (Doutorado em Microbiologia Médica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019. |
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http://www.repositorio.ufc.br/handle/riufc/43968 |
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openAccess |
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Universidade Federal do Ceará (UFC) |
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Repositório Institucional da Universidade Federal do Ceará (UFC) |
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Repositório Institucional da Universidade Federal do Ceará (UFC) |
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Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC) |
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