Antibiotic-Associated Microbiome Changes in Healthy Volunteers and Corrective Impact of the Probiotic Saccharomyces boulardii: Presidential Poster

Abstract

Introduction: The aim of this study is to evaluate the effects of an antibiotic (amoxicillin-clavulanate), a probiotic (Saccharomyces boulardii), and the combination on the microbiota of healthy adult volunteers. Methods: Healthy subjects were randomized to 1 of 4 study groups (n=12 for each): 1) Saccharomyces boulardii (SB) 500 mg twice daily for 14 days, 2) amoxicillin/clavulanate (AC) 875/125 mg twice daily for 7 days, 3) amoxicillin/clavulanate plus Saccharomyces boulardii (each dosed as above), 4) control (no treatment). Seven stool samples were collected from subjects in the active groups (groups 1, 2, and 3) and 3 stool samples from controls. Gastrointestinal symptom questionnaires were also completed by the participants. 16S DNA pyrosequencing was used to identify the predominant bacterial genera in stool samples and to monitor changes in the microbiota in each study group. Results: Subjects showed a complex microbiome at study entry that segregated into groupings or “enterotypes” as previously described. Antibiotic treatment was associated with marked microbiome changes and these persisted for some time after treatment ended. Antibiotic treatment led to a markedly reduced prevalence of the genus Ralstonia and parallel increases in Parabacteroides and Escherichia/Shigella. S. boulardii treatment alone did not substantially alter the microbiome. However, when S. boulardii was administered in combination with amoxicillin/clavulanate the antibiotic-induced changes in the genera Ralstonia, Parabacteroides and Escherichia/Shigella were significantly attenuated (P<0.05 for each). Diarrhea scores (measured using the Gastrointestinal Symptom Response Score [GSRS]) increased during antibiotic treatment in parallel with increases in the prevalence of Escherichia/Shigella in the stool (R2 0.9993 by linear regression, P<0.001). S. boulardii treatment in combination with the antibiotic prevented the increase in Escherichia/Shigella prevalence and also prevented antibiotic-associated diarrhea (P<0.05 for each). Conclusion: The microbiomes of healthy individuals show substantial diversity but remain stable over time and can be grouped into “enterotypes”. Antibiotic treatment is associated with marked microbiome changes with both reductions (Ralstonia) and increases (Parabacteroides, Escherichia/Shigella) in different genera. S. boulardii treatment can prevent some antibiotic-induced microbiome changes and, in parallel, can reduce antibiotic-associated diarrhea. Future studies are warranted to explore whether the strong correlation between an increased prevalence of Escherichia/Shigella and increased symptom scores for antibiotic-associated diarrhea represent a cause and effect association that is positively influenced by S. boulardii. Disclosure - Dr Kelly - Consultant and invited speaker, paid travel expenses: Biocodex Inc. Dr Dowd - Employee of MR DNA. This research was supported by an industry grant from Biocodex Inc.