A randomized controlled trial of postbiotic administration during antibiotic treatment increases microbiome diversity and enriches health associated taxa

Abstract

Antibiotic-induced microbiome injury, defined as a reduction of ecological diversity and obligate anaerobe taxa, is associated with negative health outcomes in hospitalized patients, and healthy individuals who received antibiotics in the past are at higher risk for autoimmune diseases. No interventions are currently available that effectively target the microbial ecosystem in the gut to prevent this negative collateral damage of antibiotics. Here, we present the results from a single-center, randomized placebo-controlled trial involving 32 patients who received an oral, fermentation-derived postbiotic alongside oral antibiotic therapy for gastrointestinal (GI)-unrelated infections. Postbiotics comprise complex mixtures of metabolites produced by bacteria during fermentation and other processes, which can mediate microbial ecology. Bacterial ecosystem alpha diversity, quantified by the inverse Simpson index, during the end of the antibiotic course was significantly higher (+40%) across the 16 postbiotic-treated patients compared with the 16 patients who received a placebo, and the postbiotic was well-tolerated. Secondary analyses of 157 stool samples collected longitudinally revealed that the increased diversity was driven by enrichment in health-associated microbial genera: obligate anaerobe Firmicutes, in particular taxa belonging to the Lachnospiraceae family, were higher in treated patients; conversely, Escherichia/Shigella abundances, which comprise pathobionts and antimicrobial-resistant strains, were reduced in postbiotic-treated patients at the end of their antibiotic course and up to 10 days later. Taken together, these results indicate that postbiotic co-administration during antibiotic therapy could support a health-associated gut microbiome community and may reduce antibiotic-induced microbiome injury.