Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus

Parul Singh,Arun Rawat,Rayaz A Malik,Bara Al-Jarrah,Mamoun Elawad,Wesam Al-Masri,Khalid Hussain,Saras Saraswathi,Mohammed A Hendaus,Souhaila Al Khodor,Hoda Gad,Anthony K Akobeng

doi:10.3390/ijms22041511

Abstract

Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (n = 19), T1DM (n = 18) and both CD and T1DM (n = 9) compared to healthy controls (n = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria Shigella and E. coli were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus Parabacteroides was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.

Highlights

Introduction conditions of the Creative CommonsType 1 diabetes (T1DM) [1] and coeliac disease (CD) [2] are two of the most frequent childhood autoimmune diseases [3,4]
The Type 1 diabetes mellitus (T1DM)+Coeliac disease (CD) group overlapped with T1DM suggesting an overall compositional similarity between the two groups. These results indicate that CD and T1DM exhibit distinct microbial composition
Patients with CD had markedly lower diversity, whereas those with T1DM had the highest diversity among the three disease groups (Figure 2). These results suggest that alterations in the gut bacterial microbiota diversity were aggravated in subjects with CD or with CD and T1DM

Summary

Introduction

Introduction conditions of the Creative CommonsType 1 diabetes (T1DM) [1] and coeliac disease (CD) [2] are two of the most frequent childhood autoimmune diseases [3,4]. T1DM is characterized by autoimmune destruction of β cells of the islets of Langerhans, causing insulin deficiency and hyperglycemia [5]. The worldwide incidence of both T1DM [7], and CD [8,9] are increasing, and the prevalence of CD in children with T1DM is 5–7 times greater than that of the general population [3]. The coexistence of these two disorders has traditionally been attributed to the sharing of common high-risk human leukocyte antigen (HLA) (HLA) genotypes (DR-DQ) [3,10]. While intestinal dysbiosis has been clearly demonstrated in patients with

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