Correlação entre o epitélio duodenal, marcadores inflamatórios, fibrose hepática e microbiota intestinal em pacientes com diferentes graus de tolerância à glicose e adiposidade corporal

• Autor(a) principal: Lopes, Fernanda de Azevedo Marques
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12567
• topic: Obesity; Microbiota; Intestinal permeability; DHGNA; Obesidade; Microbiota; Permeabilidade Intestinal; DHGNA; Obesidade; Micobiota; Resistência à insulina; Cirrose hepática; Adiposidade; Mediadores de inflamação; Biomarcadores; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::GASTROENTEROLOGIA

The role of the intestinal microbiota (MI) and its relationship to certain comorbidities in clinical studies is still poorly understood. It seems promising to us that the dysregulation of MI, associated with morphofunctional changes in the intestinal epithelium and consequent increased mucosal permeability to LPS (lipopolysaccharide), would trigger the necessary trigger for the establishment of low-grade systemic inflammation closely associated with insulin resistance and inflammatory phenotype of the obese. In this cross-sectional study we investigated the associations between inflammatory serum markers, morphofunctionality and intestinal microbiota and the degree of hepatic steatosis / fibrosis in individuals with different degrees of glucose tolerance and body adiposity. Forty-six individuals with a body mass index between 20 and 40 kg / m2, dysglycemic or not, were distributed in the control (C), obese (OB) and obese (OBD) groups. We evaluated the inflammatory and biochemical profile through serum dosages, which were performed at baseline, 30 and 60 minutes after standard meal intake. The intestinal epithelial samples were collected by means of duodenal biopsies in upper digestive endoscopy. The myosin, phosphomyosin, phosphosiosine, myosin and β-actin protein expression (Western blot) and myelin (immunohistochemistry) and intestinal alkaline phosphatase activity (enzyme assay). In order to evaluate the degree of hepatic fibrosis and steatosis, we used FibroScan® and, finally, fecal microbiota analysis by PCR (polymerase chain reaction). LPS was directly related to body fat index, as well as other inflammatory markers (tumor necrosis factor alpha (TNF-α), LPS binding protein (LBP), interleukin-6 (IL-6) and ferritin. In addition, there was an inverse relationship of the LPS in the time 60 minutes with the total thickness of the intestinal epithelium and height of the villi. Still in relation to the intestinal epithelium, β-actin was the most important structural protein, being inversely related to BMI, markers of insulin resistance, hepatic function tests and elastography indices.Intestinal alkaline phosphatase (IAF) followed a similar pattern, also being inversely related to glucose, glycated hemoglobin and gamma globulin transferase. The intestinal microbiota presented great individual variability and it was not possible to correlate any phyla to the specific parameters in the present study. In the comparison between the groups, we did not observe differences between LPS, structural proteins, histomorphometric analyzes and intestinal microbiota.The activity of FAI was higher in group C, compared to OBD, being the opposite of hepatic fibrosis and steatosis indexes, more significant in the OBD group, as expected. Importantly, we demonstrated that intestinal alkaline phosphatase is more active in lean individuals compared to obese individuals. In addition, we found direct associations between this and markers of insulin resistance. Opposite to this, we observed the probable protective role of β-actin and the relationship between certain histomorphometric variables and LPS, demonstrating that the intestinal epithelium may be altered in the inflammatory phenotype present in the metabolic syndrome. Finally, the main objectives of this research were concluded, since we could verify that there are associations between the studied parameters and we verified that the intestinal epithelium may be altered in the inflammatory phenotype present in obesity and dysglycemia, independent of the intestinal microbial profile. Such data deserve to be investigated in the future, in order to allow a better understanding of the pathophysiology of obesity and some of its comorbidities.