Objective Coeliac disease is defined by gluten responsiveness, yet there are few data on gluten challenge (GC) in adults on a gluten free diet. Lack of data regarding the kinetics of responses to gluten is a limitation in clinical practice and research when GC is performed. Design 20 adults with biopsy-proven coeliac disease participated. The study included two run-in visits followed by a 14 day GC at a randomly assigned dose of 3 or 7.5 grams of gluten/day. Study visits occurred 3, 7, 14 and 28 days after starting GC. Duodenal biopsy was performed during the run-in and at days 3 and 14 of GC. Villous height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count/100 enterocytes were measured by two pathologists. Antibodies to tTG and DGP, lactulose to mannitol ratio (LAMA), and symptoms were assessed at each visit. Results Significant reduction in Vh:Cd (2.2 to 1.1, p < 0.001) and increase in IELs (32.6 to 51.8, p < 0.001) were seen from baseline to day 14. Antibody titers increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did not change significantly. Gastrointestinal symptoms increased significantly by day 3 and returned to baseline by day 28. No differences were seen between the two gluten doses. Conclusions 14 day GC at ≥3 grams of gluten/day induces histological and serological changes in the majority of adults with coeliac disease. These data permit accurate design of clinical trials and indicate that many individuals will meet coeliac diagnostic criteria after a two week GC.

SUMMARY BackgroundCoeliac disease is increasingly diagnosed and weight changes are common after adoption of a gluten-free diet (GFD), however data on body mass index (BMI) changes are limited.

Probiotics are believed to be beneficial in maintaining a healthy gut microbiota whereas antibiotics are known to induce dysbiosis. This study aimed to examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 (SB), the antibiotic Amoxicillin-Clavulanate (AC) and the combination on the microbiota and symptoms of healthy humans.Healthy subjects were randomized to one of 4 study groups: SB for 14 days, AC for 7 days, SB plus AC, Control (no treatment). Participants gave stool samples and completed gastro-intestinal symptom questionnaires. Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing (bTEFAP).Only one subject withdrew prematurely due to adverse events. Subjects treated by S boulardii + AC had fewer adverse events and tolerated the study regimen better than those receiving the AC alone. Control subjects had a stable microbiota throughout the study period. Significant microbiota changes were noted in the AC alone group during antibiotic treatment. AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia, Parabacteroides, and Enterobacter. Microbiota alterations reverted toward baseline, but were not yet completely restored 2 weeks after antibiotherapy. No significant shifts in bacterial genera were noted in the SB alone group. Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhea scores.Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera. S. boulardii treatment can mitigate some antibiotic-induced microbiota changes (dysbiosis) and can also reduce antibiotic-associated diarrhea.

SUMMARY BackgroundDuodenal villous atrophy (DVA) is a key diagnostic finding in coeliac disease (CD). However, the differential diagnosis for this finding is broad.

On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have NCGS and may not require further testing. Those with equivocal serology should undergo HLA typing to determine the need for biopsy.