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

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.

Children Who Develop Celiac Disease Exhibit Distinct Metabolic Pathways Among Their Gut Microbiota Years Before Diagnosis

“…We found that several taxa were decreased in the age 1 CD progressor samples, such as Veillonella, Enterobacteriaceae, and Bacteriodes. This is consistent with other studies showing Veillonella decreased in CD progressors 72 , Enteriobacter decreased in infants at high risk for CD 71 and Bacteroides decreased in both CD progressors 72 and patients 69 . Consistent with our findings, other studies have shown that the abundance of B. dentium was increased in the CD patients 73 .…”

Microbial dysbiosis in the gut drives systemic autoimmune diseases

“…T1D is a systemic autoimmune disease that is linked to microbial dysbiosis. Preclinical and clinical T1D is mostly associated with GIT pathogenesis, such as celiac disease or increased intestinal leakage potentially due to microbial dysbiosis ( 41 – 43 ). Multiple studies report significant shifts in gut microbes including bacteria, viruses, and fungi before the onset of T1D as reviewed ( 44 ).…”

Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation

“…[ 114 ] suggested that gut-related inflammation elicits neuroinflammation by endocrine signals and, therefore, promotes atrophy and hyperactivity in the anterior cingulate cortex, involved in mood disorders, anxiety, and threat-related behaviors [ 114 ]. The “leaky gut” condition in CD also encourages the overproduction and release of LPS and long-chain fatty acids, which both play a central role in neuronal plasticity [ 115 , 116 ] and neurodegeneration [ 117 , 118 , 119 ].…”