Background: Coeliac disease is an immune disease, characterised by small intestinal inflammation in response to gluten. Currently, the only treatment option is Gluten Free Diet (GFD). Despite adherence to GFD, a significant proportion of coeliac patients have persistent gastrointestinal (GI) symptoms and mechanisms are not well understood. We aimed to study the impact of coeliac disease and GFD on gut function and microbiome in a group of patients before starting GFD, and after 1 year follow-up.
Methods: 36 newly diagnosed patients and 36 healthy controls were recruited. MRI was carried out at baseline and 12 month follow up to determine gut physiological parameters including small bowel water content (SBWC), whole gut transit time (WGTT) and colonic volumes. Stool samples were collected at baseline and 12 months, DNA extracted and subjected to shotgun metagenomic sequencing. DNA sequences were assembled into Metagenome Assembled Genome’s (MAGs), to estimate species level abundances and annotate gene functions, including carbohydrate active enzymes (CAZymes).
Results: At baseline, patients with CD had higher levels of somatisation, had higher scores for depression and anxiety and reported higher levels of GI symptoms. Small bowel water content was significantly increased in people with CD 157±15 mL compared to HVs 100±12 mL (p=0.003). Whole gut transit time was delayed in people with CD 68±8 hours compared to HVs 41±5 hours (p=0.002). The differences reduced after 12 months of GFD but not significantly. Wellbeing of the group of patients with CD significantly improved after GFD but did not recover to control HV values. Coeliac patient microbiome showed high abundance of proteolytic gene functions, associated with Escherichia coli, Enterobacter and Peptostreptococcus. After 12 months of GFD there were significantly reduced Bifidobacteria in coeliac patients and increased Blautia wexerelae. Microbiome composition was correlated to WGTT and colonic volume, positively with Akkermansia municphilia and negatively with B.wexerelae. Following GFD the reduction in WGTT and colonic volume, was significantly associated with increased abundance of B.wexerelae. Following GFD there were significant alterations in CAZyme profiles, specifically reductions in CAZyme families GH13 and CBM48 (starch degrading) and GH43 (arabinoxylan degrading).
Conclusion: Gut function and gut microbiota are impacted by coeliac disease, characterised by increased SBWC, slower WGTT and high abundance of proteolytic species. GFD did not reverse these gut effects. GFD resulted in a significant reduction in Bifidobacteria associated with reduced intake of resistant starch and arabinoxylan from wheat.
This potentially opens the possibility of developing dietary interventions such as increasing fibre intake or targeted prebiotic and/or synbiotic products to add to a GFD.

Falk Hildebrand

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