# A retrospectively registered pilot randomized controlled trial of postbiotic administration during antibiotic treatment increases microbiome diversity and enriches health-associated taxa

## TL;DR

This study shows that taking a postbiotic with antibiotics helps protect the gut microbiome by increasing diversity and promoting healthy bacteria.

## Contribution

The study is the first to demonstrate that a fermentation-derived postbiotic can reduce antibiotic-induced microbiome injury in humans.

## Key findings

- Patients receiving postbiotic had 40% higher fecal bacterial alpha diversity compared to the placebo group.
- Postbiotic treatment enriched health-associated obligate anaerobic Firmicutes, especially Lachnospiraceae.
- Escherichia/Shigella species were reduced in postbiotic-treated patients and remained lower for 10 days.

## 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. Postbiotics contain mixtures of bacterial fermentation metabolites and bacterial cell wall components that have the potential to modulate microbial communities. Yet, it is unknown if a fermentation-derived postbiotic can reduce antibiotic-induced microbiome injury. 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 and probiotic therapy for non-gastrointestinal (GI) infections. At the end of the antibiotic course, patients receiving the postbiotic (n = 16) had significantly higher fecal bacterial alpha diversity (+40%, inverse Simpson index) compared to the placebo group (n = 16), and the treatment was well-tolerated. Analysis of 157 longitudinal fecal samples revealed that this increased diversity was driven by enrichment of health-associated taxa, notably obligate anaerobic Firmicutes, particularly Lachnospiraceae. In contrast, Escherichia/Shigella species, often linked to pathogenicity and antibiotic resistance, were reduced in postbiotic-treated patients at the end of antibiotic treatment and remained lower up to 10 days later. Our findings suggest that postbiotic co-administration during antibiotic therapy may augment health-associated gut microbiome composition and mitigate antibiotic-induced microbiome injury.

Trial registration ISRCTN30327931 retrospectively registered.