GABA-Producing Levilactobacillus brevis LAB6 Mitigates Pentylenetetrazol-Induced Gut-Brain Dysregulation in SD Rats

Abstract

Understanding the communication between the gut and brain has emerged as a new research avenue in neurological disorders like epilepsy, with increasing evidence pointing towards the influence of intestinal microbes on the central nervous system. Here, the protective effects of a psychobiotic strain Levilactobacillus brevis LAB6 MTCC 25662 supplementation against pentylenetetrazole (PTZ)-induced kindling in male Sprague Dawley rats was studied. Two GABA-producing strains Levilactobacillus brevis LAB6 and Limosilactobacillus fermentum LAB19 were screened for their protective effects against chronic PTZ-induced kindling. Chronic subconvulsive PTZ administration increased the convulsive activity, ultimately leading to generalized tonic–clonic seizures as indicated by a progressive rise in the seizure score, changes in endogenous antioxidants, and changes in inflammatory cytokines. Intervention with LAB6, but not LAB19, significantly attenuated these alterations and beneficially modulated gut health by increasing the production of short-chain fatty acids and promoting healthy gut microbes, suggesting strain-specific effects of LAB6. Further, colonization study with indocyanine green (ICG) labeled LAB6 was done, followed by dose-dependent protective efficacy of LAB6 in PTZ-induced kindling. A single dose administration (10¹⁰ CFU) showed that LAB6 translocated and adhered throughout the gastrointestinal (GI) tract within 8 h of administration and reached the distal colon and cecum. The supplementation of LAB6 at a medium dose of 2 × 10¹⁰ CFU was most efficient in restoring altered gut barrier functions, behavioral deficits, and modulation of peripheral GABA levels. Hence, it is a promising psychobiotic candidate for positively modulating gut-brain functions in epilepsy.