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.

Postbiotic administration during antibiotic treatment increases bacterial alpha diversity

Characteristic bacterial signatures are associated with postbiotic administration

Health-associated taxa are enriched and disease-associated taxa are reduced by postbiotic treatment

AL is CEO of Postbiotics Plus Research. AL and JS are co-founders of Postbiotics Plus Research. AL, JS, EL, KRF, JUP hold equity in Postbiotics Plus Research. JUP reports research funding, intellectual property fees, and travel reimbursement from Seres Therapeutics, and consulting fees from DaVolterra, CSL Behring, and from MaaT Pharma. JUP has filed intellectual property applications related to the microbiome (reference numbers #62/843,849, #62/977,908, and #15/756,845). Memorial Sloan Kettering Cancer Center (MSK) has financial interests relative to Seres Therapeutics. AL and JS have filed intellectual property applications related to the microbiome (reference numbers #63/299,607). JUP and KRF serve on an Advisory board of Postbiotics Plus Research. JS serves on an Advisory board and holds equity of Jona Health.

Randomized controlled trial of PBP-GP-22 to affect microbiome composition; https://www.isrctn.com; trial registration ISRCTN30327931

JS reports funding from the National Institutes of Health (NIH) grants DP2 AI164318-01, and R01CA269617. FM is supported by a Helen Hay Whitney Fellowship. JUP reports funding from NHLBI NIH Award K08HL143189, the MSKCC Cancer Center Core Grant NCI P30 CA008748.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study protocol was reviewed and approved by the New England Institutional Review Board, and independent IRB located in Needham, MA (number: 120180088, trial registration ID: ISRCTN30327931.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data, statistical test results, and relevant code to reproduce main analyses are available as supplementary materials. The 16S rRNA gene sequencing results are available as supplementary data files (Table S3). Raw sequencing reads are available on the sequencing read archive, submission SUB13922145.