Persistent gut microbiota dysbiosis and metabolic remodeling after ceftriaxone exposure in mice: a cross-study...

Broad-spectrum antibiotics are known to disrupt the gut microbial environment, which can lead to sustained physiological consequences. Ceftriaxone (CTX) is a β-lactam antibiotic widely used in neuroscience research to enhance expression of the glutamate transporter GLT-1, a key regulator of excitatory neurotransmission in the brain. However, CTX also induces marked alterations in gut microbial composition, yet the consistency and functional consequences of these changes across studies remain poorly defined.

Here, we conducted a cross-study re-analysis of four independent, publicly available murine 16S rRNA gene sequencing datasets to identify robust microbial and metabolic responses to CTX exposure. Using a bioinformatic pipeline for taxonomic annotation and functional inference, we evaluated microbial diversity, community composition, and predicted functional pathways across studies.

CTX treatment consistently reduced gut microbial diversity and altered community composition relative to controls, with only partial recovery over time. Predicted microbial functions were extensively remodeled, with CTX-exposed communities showing enrichment in pathways related to aromatic compound and amino acid metabolism, amine metabolism, and stress response, whereas control communities retained higher biosynthetic potential.

These findings demonstrate that CTX exposure induces persistent, system-level restructuring of the gut microbiome, with potential detriment to host physiology.