Avaliação da microbiota intestinal, biomarcadores inflamatórios e reatividade vascular em pacientes com diferentes graus de tolerância à glicose e adiposidade corporal antes e após dieta padrão

Abstract

For more than a decade, there are studies aiming gut microbiota, and many findings in literature are still conflicting. In this cross-sectional study, we investigated associations among gut microbiota, inflammatory biomarkers and microvascular reactivity in lean and obese individuals, diabetics or not. Forty-six individuals were included in the study and classified into three groups: controls (C), obese (OB) and obese diabetic or dysglycemic (OBD). We performed the study of microcirculation through LASER-Doppler flowmetry (LDF) and digital tonometry (EndoPat®). Moreover, evaluated the following inflammatory markers: tumor necrosis factor (TNF), interleukin-6 (IL6), bacterial lipopolysaccharide (LPS), LPS binding protein (LBP), leptin, adiponectin, ghrelin, glucagon-like peptide type-1 (GLP1) and retinol binding protein 4 (RBP4). Among the biochemical markers, we evaluated: glucose, insulin, insulin resistance index evaluated by homeostatic model assessment insulin resistance (HOMA-IR) and lipid profile. Some metabolites and markers (glucose, insulin, LPS, ghrelin, GLP1) were measured serially at baseline, 30 and 60 min; after food intake, while others (TNF, IL6, LBP, lipid profile, HOMA-IR, leptin, adiponectin and RBP4) only at the basal time (0 min). The diet of choice was Nutridrink®, a balanced liquid and standardized diet. Similarly, digital tonometry was performed at the initial and final times (60 min) while the LDF was performed continuously throughout the whole evaluation period. We tested the usual diet of each person by food frequency questionnaire, body composition by electric bioimpedance and gut microbiota, by characterization of bacterial 16s DNA. Comparisons were made aiming at the identification of differences between microbiota, metabolism, and inflammation among study groups, possibly caused, by differences in diet and body composition, besides other factors. Correlations were also made to evaluate the association among anthropometric markers of adiposity, metabolic and inflammatory features with gut microbiota. We did not find any statistically significant differences for most of the dietary macronutrients evaluated, possibly reflecting the little difference found in gut microbiota. In an original way, we observed a temporal decrease of the LPS curve in all groups, concurrently, although it only reached statistical significance in the OB group and showed a tendency to significance in the C group. We have established essential correlations among biochemical, inflammatory and microvascular markers that confirm outstanding concepts of metabolic diseases' physiology and their association with systemic inflammation; such as the negative relationship between the area under the glucose curve and the rate of reactive hyperemia, the positive correlation between triglycerides and LPS and IL6. Reinforcing with the complexity of the subject, we did not identify any distinctive pattern of gut microbiota in any of the evaluated groups. We hope this work may contribute to that new hypotheses will be tested in the study of the relationship between gut microbiota and metabolism in humans.