Abstract

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.

Highlights

  • Type 1 diabetes (T1D) or autoimmune diabetes is a chronic disease mediated by immune reactions against pancreatic beta cells, resulting in insulin dependence to regulate blood glucose con­ centrations [1]

  • To evaluate the dietary habits in type 1 diabetes (T1D) patients and healthy controls, we applied a questionnaire about daily consumption of vegetables, fresh fruit, carbohydrates, proteins, trans fat, milk and derivatives, spicy food, canned food, hot drinks, and alcohol

  • To find correlations between dietary habits and microbial community, we analyzed the correlations among consumption of vegetables, fresh fruit, carbohydrates, proteins, trans fat, milk and derivatives, spicy food, canned food, hot drinks, and alcohol with relative abundances of the gut microbiota detected in stool samples from T1D patients

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Summary

Introduction

Type 1 diabetes (T1D) or autoimmune diabetes is a chronic disease mediated by immune reactions against pancreatic beta cells, resulting in insulin dependence to regulate blood glucose con­ centrations [1]. The T1D pathogenesis involves the interaction of genetic and environmental factors, such as viral infections, vitamin deficiencies, and intestinal dysbiosis [2]. According to the International Diabetes Federation, more than 96,000 children and adolescents under 15 years will be diagnosed with auto­ immune diabetes annually worldwide [3]. An impaired tolerance pro­ cess in infancy can predispose to develop autoimmune diseases, such as T1D, and might induce autoreactive T cell activation and autoantibodies [4]. Intestinal dysbiosis may lead children with genetic predisposition and positive auto­ antibodies to develop clinical disease [4]

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