Beneficial Modulation of the Microbiota-Gut-Brain Axis by Supplementation with Modified Kodo Millet Bran and a GABA-Producing Bacterium in PTZ-Induced Kindling.

Beneficial modulation of the microbiota-gut-brain axis (MGBA) using dietary fibres and psychobiotics has emerged as a novel strategy for the management of various neurological conditions including epilepsy. Herein, we investigated the effects of supplementation of modified kodo millet bran (mKMB) along with GABA-producing Levilactobacillus brevis LAB6 MTCC 25662 in mitigating epileptic seizures, neuroinflammation and colonic aberrations in pentylenetetrazol (PTZ)-induced epilepsy in SD rats. Chronic PTZ kindling induced gut-brain dysregulation, whereas supplementation with mKMB and LAB6 reduced seizure severity, preserved neuronal spines, and restored hippocampal GABAergic function. It also effectively attenuated neuro- and systemic inflammation (~ 1.77-fold overall cytokine reduction), associated with enhanced FFAR2/3 expression and increased gut GABA and SCFAs. Microbiome analysis showed that supplementation mitigated kindling-induced dysbiosis by reducing Aerococcus, Clostridium, Enterococcus and enriching beneficial microbes; notably, Turicibacter abundance increased to 21.39% in Syn + PTZ compared to 13.6% in PTZ (log₂FC = + 0.65, p = 0.056) and 17.21% in mKMB + PTZ (log₂FC = + 0.56, p = 0.032), alongside an increase in Lactobacillus, particularly Levilactobacillus brevis. These findings highlight the protective potential of dietary fibres and rationale psychobiotics supplementation in modulating MGBA and developing an effective management strategy for epilepsy.