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

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Leite, Aline Zazeri ; Rodrigues, Nathalia de Campos ; Gonzaga, Marina Ignacio ; Cicogna Paiolo, Joao Carlos ; de Souza, Carolina Arantes ; Vicentini Stefanutto, Nadine Aparecida ; Omori, Wellington Pine ; Pinheiro, Daniel Guariz ; Brisotti, Joao Luiz ; Matheucci Junior, Euclides ; Mariano, Vnia Sammartino ; Vilela de Oliveira, Gislane Lelis

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 8, SEP 15 2017.
• Citações Web of Science: 16

Resumo

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. (AU)

• Processo FAPESP: 16/50204-0 - Sequenciamento de DNA de segunda geração (NGS) aplicado ao diagnóstico em microbiologia clínica
• Beneficiário: Nathalia de Campos Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE
• Processo FAPESP: 17/18070-6 - Detection of increased plasma IL-6 levels and prevalence of Prevotella copri and Bacteroides vulgatus in the feces of type 2 diabetes patients
• Beneficiário: Gislane Lelis Vilela de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo