Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis.

Hashimoto thyroiditis (HT) is the most common autoimmune disease worldwide, characterized by chronic inflammation and circulating autoantibodies against thyroid peroxidase and thyroglobulin. Patients require hormone replacement with oral levothyroxine, and if untreated, they can develop serious adverse health effects and ultimately death. There is a lot of evidence that the intestinal dysbiosis, bacterial overgrowth, and increased intestinal permeability favor the HT development, and a thyroid-gut axis has been proposed, which seems to impact our entire metabolism. Here, we evaluated alterations in the gut microbiota in Brazilian patients with HT and correlated this data with dietary habits, clinical data, and systemic cytokines and zonulin concentrations. Stool samples from 40 patients with HT and 53 controls were analyzed using real-time PCR, the serum cytokine levels were evaluated by flow cytometry, zonulin concentrations by ELISA, and the dietary habits were recorded by a food frequency questionnaire. We observed a significant increase (p < 0.05) in the Bacteroides species and a decrease in Bifidobacterium in samples of patients with HT. In addition, Lactobacillus species were higher in patients without thyroid hormone replacement, compared with those who use oral levothyroxine. Regarding dietary habits, we demonstrated that there are significant differences in the consumption of vegetables, fruits, animal-derived proteins, dairy products, saturated fats, and carbohydrates between patients and control group, and an inverse correlation between animal-derived protein and Bacteroides genus was detected. The microbiota modulation by diet directly influences the inflammatory profile due to the generated microbiota metabolites and their direct or indirect action on immune cells in the gut mucosa. Although there are no differences in systemic cytokines in our patients with HT, we detected increased zonulin concentrations, suggesting a leaky gut in patients with HT. These findings could help understand the development and progression of HT, while further investigations to clarify the underlying mechanisms of the diet-microbiota-immune system axis are still needed.

Intestinal Dysbiosis in Autoimmune Diabetes Is Correlated With Poor Glycemic Control and Increased Interleukin-6: A Pilot Study.

Intestinal dysbiosis associated with immunological deregulation, leaky gut, bacterial translocation, and systemic inflammation has been associated with autoimmune diseases, such as type 1 diabetes (T1D). The aim of this study was to investigate the intestinal dysbiosis in T1D patients and correlate these results with clinical parameters and cytokines. The present study was approved by the Barretos Cancer Hospital (Process number 903/2014), and all participants have signed the informed consent in accordance with the Declaration of Helsinki, and answered a questionnaire about dietary habits. Stool samples were used for bacterial 16S sequencing by MiSeq Illumina platform. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF, and IFN-γ plasma concentrations were determined by cytometric bead arrays. The Pearson's chi-square, Mann-Whitney and Spearman correlation were used for statistical analyses. Alpha and beta diversities were conducted by using an annotated observed taxonomic units table. This study included 20 patients and 28 controls, and we found significant differences (P < 0.05) among consumption of vegetables, proteins, milk and derivatives, spicy food, and canned food when we compare patients and controls. We detected intestinal dysbiosis in T1D patients when we performed the beta diversity analysis (P = 0.01). The prevalent species found in patients' stool were the Gram-negatives Bacteroides vulgatus, Bacteroides rodentium, Prevotella copri, and Bacteroides xylanisolvens. The inflammatory interleukin-6 was significantly increased (P = 0.017) in patients' plasma. Furthermore, we showed correlation among patients with poor glycemic control, represented by high levels of HbA1C percentages and Bacteroidetes, Lactobacillales, and Bacteroides dorei relative abundances. We concluded that there are different gut microbiota profiles between T1D patients and healthy controls. The prevalent Gram-negative species in T1D patients could be involved in the leaky gut, bacterial translocation, and poor glycemic control. However, additional studies, with larger cohorts, are required to determine a "signature" of the intestinal microbiota in T1D patients in the Brazilian population.

Detection of Increased Plasma Interleukin-6 Levels and Prevalence of Prevotella copri and Bacteroides vulgatus in the Feces of Type 2 Diabetes Patients.

Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D). The main goal of the present study was to evaluate the intestinal dysbiosis in Brazilian T2D patients and correlate these data with inflammatory cytokines and lipopolysaccharides (LPS) plasma concentrations. This study was approved by the Ethics Committees from Barretos Cancer Hospital and all individuals signed the informed consent form. Stool samples were required for DNA extraction, and the V3/V4 regions of bacterial 16S were sequenced using an Illumina platform. Peripheral blood was used to quantify inflammatory cytokines and plasma LPS concentrations, by CBA flex and ELISA, respectively. Statistical analyses were performed using Mann-Whitney and Spearman's tests. Analysis of variance, diversity indexes, and analysis of alpha- and beta-diversity were conducted using an annotated Operational Taxonomic Unit table. This study included 20 patients and 22 controls. We observed significant differences (P < 0.01) in the microbiota composition (beta-diversity) between patients and controls, suggesting intestinal dysbiosis in Brazilian T2D patients. The prevalent species found in patients' feces were the Gram-negatives Prevotella copri, Bacteroides vulgatus, Bacteroides rodentium, and Bacteroides xylanisolvens. The proinflammatory interleukin-6 (IL-6) was significantly increased (P < 0.05) in patients' plasma and LPS levels were decreased. We find correlations between the proinflammatory interferon-gamma with Gram-negatives Bacteroides and Prevotella species, and a positive correlation between the LPS levels and P. copri reads. The P. copri and B. vulgatus species were associated with insulin resistance in previous studies. In this study, we suggested that the prevalence of Gram-negative species in the gut and the increased plasma IL-6 in patients could be linked to low-grade inflammation and insulin resistance. In conclusion, the P. copri and B. vulgatus species could represent an intestinal microbiota signature, associated with T2D development. Furthermore, the identification of these Gram-negative bacteria, and the detection of inflammatory markers, such as increased IL-6, could be used as diabetes predictive markers in overweight, obese and in genetically predisposed individuals to develop T2D.

Aspectos básicos da lesão de isquemia e reperfusão e do pré-condicionamento isquêmico / Basic aspects of the ischemia reperfusion injury and of the ischemic preconditioning

A isquemia tem papel fundamental em muitas situações clínicas perioperatórias. Apesar da revascularização sanguínea a um órgão isquêmico seja essencial para prevenir a irreversibilidade da lesão celular, a reperfusão pode agravar as lesões produzidas na fase isquêmica isolada. Assim, o dano celular induzido após reperfusão de um órgão isquêmico é denominado de lesão de isquemia-reperfusão (I/R). Aspectos básicos da lesão IIR, são revisados neste artigo.

Efeito da deferoxamina na isquemia e reperfusäo do fígado remanescente após ressecçäo hepática parcial / Effect of deferoxamine in ischemia and reperfusion remaining after partial hepatic resection

Particularmente, a utilização de vários tipos de drogas que diminuem os efeitos deletérios do binômio isquemia-reperfusão, tem tornado-se foco de vários estudos experimentais visando possíveis aplicações clínicas. O objetivo do presente estudo foi avaliar os efeitos da deferoxamina na isquemia e reperfusão sobre o fígado remanescente após ressecção hepática parcial a 70 por cento, avaliando-se váriáveis bioquímicas do sangue: aspartato aminotransferase e alanina aminotransferase;.A amostra de 34 ratos foi dividida em grupos: Grupo HP (n = 8) - submetidos a hepatectomia parcial (HP) a 70 por cento; Grupo HPD (n = 4) - submetidos a administração de deferoxamina (40 mg/kg) e HP a 70 por cento; Grupo HPI (n = 7) - hepatectomizados (HP a 70 por cento) e submetidos a isquemia (40 minutos); Grupo HPID (n = 7) - semelhante ao anterior, porém recebendo previamente deferoxamina; Grupo C (n = 8) - controle, submetido a operação simulada para HP a 70 por cento. A análise estatística entre os diversos grupos foi feita pelos testes de Kruskal - Wallis e de Mann - Whitney, com nível de significância de 5 por cento. Portanto, houve aumento significativo das aminotransferases nos animais submetidos a hepatectomia e a isquemia. Esse aumento foi inibido pela deferoxamina.