Changes to the Composition of the Gastrointestinal Microbiome after Probiotics for Clostridium difficile Infection in Adults

BACKGROUND: Clostridium difficile infections (CDI) in the US have markedly increased. Disturbances to the gastrointestinal (GI) microbiome due to antibiotic use predisposes patients to CDI. Probiotics are recommended to prevent GI microbiota changes during CDI antibiotic treatment, but efficacy is unknown. We conducted a randomized, double-blinded, placebo-controlled, examination of clinical and GI microbiota changes in subjects administered probiotics during a primary episode of CDI. METHODS: 33 subjects with a primary episode of CDI were randomized to once daily oral probiotic, consisting of four different bacterial strains, or placebo for 4-weeks (week 0–4) concurrent to antibiotic treatment. Subjects completed a daily stool diary, and stool samples were collected at enrollment (week 0), at the end of the probiotic or placebo adjunct regimen (week 4), and 4 weeks post-treatment (week 8). DNA was extracted for 16S rRNA sequencing with Illumina MiSeq. Microbial diversity, richness, and community structure were compared using analysis of variance and permutational analysis of variance. Similarity percentage analysis identified the operational taxonomic units driving the variation in β diversity. RESULTS: The duration of diarrhea (P = 0.039) and total days of diarrhea (P = 0.005) both decreased in the probiotic group compared with the placebo group. Analysis of community structure showed significant differences between treatment groups overall (P = 0.017) and in both groups over time (P = 0.007), but not between groups at each individual time point. Subjects in the probiotic group had a higher abundance of the family Lachnospiraceae at week 4 than subjects in the placebo group. By week 8 the abundance of Lachnospiraceae did not differ between subjects administered probiotic or placebo. CONCLUSION: Lack of difference in overall community structure between groups at each time point is likely due to concurrent antibiotic therapy. The differential abundance of Lachnospiraceae likely contributes to the differences in the diarrheal outcomes observed between groups, as it has previously been associated with attenuated C. difficile pathology. Shortening the duration of diarrhea from an initial CDI may reduce the spread of C. difficile and improve clinical outcomes. DISCLOSURES: All authors: No reported disclosures.