Gluten-free diet affects faecal small non-coding RNA profiles and microbiome composition in celiac disease supporting a host-gut microbiota crosstalk. Gluten-free diet affects faecal small non-coding RNA profiles and microbiome composition in celiac disease supporting a host-gut microbiota crosstalk

The current treatment for Celiac Disease (CD) is adhering to a gluten-free diet (GFD), although its long-term molecular effects are still undescribed. New molecular features detectable in faecal samples may improve and facilitate non-invasive clinical management of CD on GFD. For this purpose, faecal small non-coding RNAs (sncRNAs) and gut microbiome profiles were concomitantly explored in CD subjects in relation to strict (or not) GFD adherence over time. In the present observational study, we performed small RNA and shotgun metagenomic sequencing in stool from 63 treated CD (tCD) subjects and 66 sex- and age-matched healthy controls. tCD included 51 individuals on strict GFD and with negative transglutaminase (TG) serology (tCD-TG-) and 12 symptomatic with not strict/short-time of GFD adherence and positive TG serology (tCD-TG+). Samples from additional 40 adult healthy individuals and from a cohort of 19 untreated paediatric CD subjects and 19 sex/age matched controls were analyzed to further test the outcomes. Several miRNA, other sncRNA (piRNA and tRNA) and microbiota profiles were altered in tCD subjects(adj.p18 and no concomitant gastrointestinal disorders (e.g., allergies/intolerances, diabetes, inflammatory bowel diseases, or tumours). The TG IgA levels were measured in serum samples of all subjects who provided blood for the present study, unless not already clinically tested in concomitance with the recruitment. All participants signed informed consent to participate in the study and received two questionnaires from the European Prospective Investigation into Cancer and Nutrition (EPIC) study (one on dietary habits and another, sex-specific, about lifestyle habits) and a disposable container for stool collection. Small RNA sequencing and shotgun metagenomic sequencing was performed on all fecal samples collected.