Abstract

The gut microbiota has been presumed to have a role in the pathogenesis of type 1 diabetes (T1D). Significant changes in the microbial composition of T1D patients have been reported in several case-control studies. This study is aimed at systematically reviewing the existing literature, which has investigated the alterations of the intestinal microbiome in T1D patients compared with healthy controls (HCs) using 16S ribosomal RNA-targeted sequencing. The databases of MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched until April 2019 for case-control studies comparing the composition of the intestinal microbiome in T1D patients and HCs based on 16S rRNA gene sequencing techniques. The Newcastle-Ottawa Scale was used to assess the methodological quality. Ten articles involving 260 patients with T1D and 276 HCs were included in this systematic review. The quality scores of all included studies were 6–8 points. In summary, a decreased microbiota diversity and a significantly distinct pattern of clustering with regard to β-diversity were observed in T1D patients when compared with HCs. At the phylum level, T1D was characterised by a reduced ratio of Firmicutes/Bacteroidetes in the structure of the gut community, although no consistent conclusion was reached. At the genus or species level, T1D patients had a reduced abundance of Clostridium and Prevotella compared with HCs, whereas Bacteroides and Ruminococcus were found to be more enriched in T1D patients. This systematic review identified that there is a close association between the gut microbiota and development of T1D. Moreover, gut dysbiosis might be involved in the pathogenesis of T1D, although the causative role of gut microbiota remains to be established. Further well-controlled prospective studies are needed to better understand the role of the intestinal microbiome in the pathogenesis of T1D, which may help explore novel microbiota-based strategies to prevent and treat T1D.

Highlights

  • Type 1 diabetes (T1D) is a chronic autoimmune disease characterised by the immune-mediated destruction of insulinproducing pancreatic beta cells, usually occurring in children and young adults [1,2,3]

  • After reviewing the full text, 30 studies were excluded for the following reasons: (1) 13 studies used other microbial detection methods rather than 16S ribosomal RNA (rRNA) gene sequencing; (2) cases of 11 studies were prediabetic subjects with islet autoimmunity, not established T1D patients; (3) 3 studies did not contain a healthy control group; (4) 2 studies provided irrelevant outcomes; and (5) 1 study was not written in English

  • In the present study, considering that the method of bacterial analysis might be an affecting factor for microbial identification, we explored the shifts of the intestinal microbiome in T1D patients based on 16S rRNA-targeted sequencing to minimise the methodology-based heterogeneity

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Summary

Introduction

Type 1 diabetes (T1D) is a chronic autoimmune disease characterised by the immune-mediated destruction of insulinproducing pancreatic beta cells, usually occurring in children and young adults [1,2,3]. There is still some uncertainty about the aetiology of T1D, it is currently considered a multifactorial autoimmune disorder involving both genetic predisposition and environmental factors [4, 5]. There has been growing evidence suggesting that gut dysbiosis may be a major contributor to T1D development [12]. Growing evidence from well-controlled intervention studies in rodent models has supported the causative association between gut dysbiosis and T1D pathogenesis. The methods commonly used in these studies to alter the composition of gut microbiota include the use of probiotics, the use of antibiotics, fecal microbiota transplantation, and diet intervention. It has been proposed that the altered intestinal microbiota may impact

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