Person:

Leffler, Daniel

ABSTRACT 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.

Background A major deficit in understanding and improving treatment in coeliac disease (CD) is the lack of empiric data on real world gluten exposure.

Aims To estimate gluten exposure on a gluten‐free diet (GFD) using immunoassays for gluten immunogenic peptides (GIP) and to examine relationships among GIP detection, symptoms and suspected gluten exposures

Methods Adults with biopsy‐confirmed CD on a GFD for 24 months were recruited from a population‐based inception cohort. Participants kept a diary and collected urine samples for 10 days and stools on days 4‐10. ‘Doggie bags’ containing ¼ portions of foods consumed were saved during the first 7 days. Gluten in food, stool and urine was quantified using A1/G12 ELISA.

Results Eighteen participants with CD (12 female; age 21‐70 years) and three participants on a gluten‐containing diet enrolled and completed the study. Twelve out of 18 CD participants had a median 2.1 mg gluten per exposure (range 0.2 to >80 mg). Most exposures were asymptomatic and unsuspected. There was high intra‐individual variability in the interval between gluten ingestion and excretion. Participants were generally unable to identify the food.

Conclusions Gluten exposure on a GFD is common, intermittent, and usually silent. Excretion kinetics are highly variable among individuals. The amount of gluten varied widely, but was typically in the milligram range, which was 10‐100 times less than consumed by those on an unrestricted diet. These findings suggest that a strict GFD is difficult to attain, and specific exposures are difficult to detect due to variable time course of excretion.