E. Coli Nissle 1917 Attenuates Antibiotic Mediated Neurotoxicity Possibly Through Gut-Brain Axis in Zebrafish

The indiscriminate use of antibiotics can disrupt the gut microbiota, and recent studies provide growing evidence for the critical role of the gut-brain axis in sustaining neurological health. This study investigated the antibacterial, neurobehavioral, and biochemical effects of five commonly used antibiotics, namely, amoxicillin, azithromycin, ciprofloxacin, rifampicin, and oxytetracycline. The neuroprotective function of the probiotic E.coli Nissle 1917 (EcN1917) was studied in vivo using zebrafish exposed to various antibiotics. Systematic behavioral analysis revealed that the antibiotics significantly impaired zebrafish behavior, while EcN1917 administration improved these behavioral deficits. The histopathological, oxidative stress and inflammatory marker analyses confirmed that antibiotics treatment caused significant damage to the zebrafish brain tissue, which was substantially mitigated following the administration of EcN1917. To demonstrate that the neuroprotective effect of EcN1917 could be mediated through strengthening of the gut-brain axis via the preservation of gut microbiota, we employed Lactobacillus rhamnosus (L. rhamnosus), a well-characterized gut microbe known for producing neuroactive compounds such as GABA, serotonin, and dopamine, as a representative commensal for the in vitro analysis. The results obtained indicate that EcN1917 promotes the survival of L. rhamnosus during antibiotic challenge. These findings suggest that EcN1917 has promising therapeutic potential to mitigate antibiotic‑induced neurotoxicity, possibly by promoting the survival of commensal bacteria in the gut and thereby influencing brain neurochemical balance possibly through gut-brain axis.