Exploring the impact of gut microbiota on epilepsy pathogenesis in Krushinsky–Molodkina rats

The gut–brain axis represents a bidirectional communication network that integrates neural, endocrine, and immune pathways with intestinal microbiota-derived signals. Disruption of this system, often resulting from gut microbiota dysbiosis, has been increasingly associated with neurological and psychiatric disorders, including depression, Alzheimer’s disease, and Parkinson’s disease. Understanding a crosstalk between host genetics, microbiota composition, and neuroinflammatory processes is therefore crucial for elucidating the mechanisms underlying brain health and disease. In the present study, we investigated gut microbiota composition in two genetically distinct rat Wistar and Krushinsky–Molodkina (KM) strains, and further assessed the effects of kindling-induced epileptogenesis and associated neuroinflammation on the KM microbiota. Our analyses revealed notable inter-group alterations in microbial composition. In particular, Enterococcus hirae abundance differed significantly between Wistar and KM control rats, while Streptococcus hyointestinalis exhibited changes between the KM control and KM kindling groups. Furthermore, we observed a reduced relative abundance of Lactobacillus murinus and Lactobacillus reuteri in KM control rats compared with both Wistar and KM kindling animals. In parallel, we observed altered expression of NF-κB p65 in the temporal lobe white matter. Specifically, Wistar vs KM control rats displayed lower NF-κB p65 expression, whereas KM kindling rats showed reduced expression compared to the KM control group. Such alterations in NF-kB p65 expression correlate with observed shifts in abundance of Lactobacillus murinus and Lactobacillus reuteri, suggesting a link between microbiota composition and neuroinflammatory processes. These findings provide deeper insight into the multifaceted interplay between host genetic background, neuroinflammation, and gut microbial composition. The results suggest that differences in bacterial taxa, particularly within Lactobacillus species, may be linked to NF-κB-mediated processes in the brain, thereby shaping the pathophysiological landscape of neurological disorders. Further investigations are required to better understand the complex crosstalk between host genetics, brain and gut microbiota, and their implication for health and disease.