Probiotic supplementation during antibiotic treatment is unjustified in maintaining the gut microbiome diversity: a systematic review and meta-analysis

Randomized controlled trials enrolling adults, adolescents, and neonates undergoing antibiotic therapy with concurrent probiotic supplementation, compared with antibiotic therapy alone. Designs included open-label, single- and multicenter double-blind, and placebo-controlled RCTs conducted across multiple countries (e.g., USA, Canada, UK, Finland, China, Korea, Japan, Ecuador, Italy). Outcomes focused on gut microbiome diversity and composition measured by 16S rRNA sequencing or other microbiological methods.

Oral probiotic supplementation during antibiotic therapy. Regimens varied across trials: Saccharomyces boulardii CNCM I-745 (e.g., 22.5 × 10^9 CFU/day) for 14 days; Clostridium butyricum (3 × 40 mg/day) for 14 days; multi-strain Lactobacillus/Bifidobacterium combinations totaling up to 1.7 × 10^10 CFU/day for 28 days; Saccharomyces boulardii CNCM I-745 (2 × 500 mg/day) for 14 days; Enterococcus faecium 129 BIO 3B-R (3 tablets/day) for 7 days; and other regimens including Lactobacillus, Bifidobacterium, Streptococcus faecium, Bacillus subtilis, Bacillus clausii, Enterococcus faecalis, Lactobacillus rhamnosus, Lactobacillus helveticus, and Bifidobacterium longum in various daily doses and durations (7–28 days). All regimens were oral during antibiotic therapy.

Probiotic supplementation during antibiotic therapy did not significantly preserve gut microbiome diversity. Across Shannon, Chao1, and observed OTUs indices, pooled differences were not statistically significant (Shannon MD 0.23, 95% CI −0.06 to 0.51; Chao1 MD 11.59, 95% CI −18.42 to 41.60; Observed OTUs MD 17.15, 95% CI −9.43 to 43.73). Most other indices showed no clear difference; taxa shifts tended to resemble baseline in both groups, with restoration toward baseline after 3–8 weeks. Conclusion: routine probiotic use during antibiotic therapy is not supported for maintaining gut microbiome diversity; standardization of diversity measures and further research are needed. Some studies noted genus-level changes (e.g., maintenance of Bifidobacterium; temporary reductions in Bacteroides; Enterobacteriaceae changes) but these did not translate into consistent diversity benefits.

Small number of eligible studies with limited sample sizes; high heterogeneity in antibiotic regimens, probiotic strains/doses, and indications; several outcomes not amenable to meta-analysis due to reporting differences; baseline group differences in some trials; overall certainty of evidence rated low.