Microbiome changes in healthy volunteers treated with GSK1322322, a novel antibiotic targeting bacterial peptide deformylaseOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study examined how GSK1322322, a novel antibacterial agent that inhibits bacterial peptide deformylase, affects the gastrointestinal microbiota. Researchers used next-generation sequencing of bacterial 16S rRNA genes in stool samples to compare the gut microbiota before dosing and at the end of the study. The drug was tested in a phase I, randomized, double-blind, placebo-controlled design, given either intravenously alone or as an oral-intravenous combination across single- and repeat-dose-escalation infusions.
Who was studied?
The study population consisted of 61 healthy volunteers who provided stool samples at predosing and end-of-study time points. Participants were assigned to placebo, intravenous-only GSK1322322, or oral-intravenous combination GSK1322322 treatment groups. The abstract does not report additional demographic details such as age or sex distribution.
What were the most important findings?
Placebo and intravenous-only treatment produced no significant changes in the relative abundance of gastrointestinal operational taxonomic units between the prestudy and end-of-study samples. Oral-intravenous treatment, however, caused significant decreases in Firmicutes and Bacteroidales and significant increases in Betaproteobacteria, Gammaproteobacteria, and Bifidobacteriaceae. Microbiome diversity plots clearly separated the end-of-study oral-intravenous samples from all other samples, and inferred genome function pointed to increased bacterial transporter and xenobiotic metabolism pathways in this group. A phylogenetic analysis of peptide deformylase sequences suggested that antibiotic target homology is one factor shaping how gut bacteria respond to the drug.
What are the greatest implications of this study?
The findings indicate that route and regimen of antibiotic dosing, not just the drug's mechanism of action, materially determine its impact on the gut microbiota. Because oral-intravenous administration produced distinct, measurable shifts while intravenous-only dosing did not, dosing strategy could be used to help limit disruption of the gastrointestinal microbiome during antibiotic development. The results also suggest that target homology across bacterial species should be considered when predicting an antibiotic's off-target effects on commensal populations.