Work

Intestinal Klebsiella pneumoniae enhances neuroinflammation and seizure susceptibility in a pentylenetetrazole-induced acute seizure model

Year: 2026

Type: article

Abstract: Epilepsy is characterized by recurrent seizures and is driven in part by neuroinflammation-induced disruption of neuronal excitation-inhibition (E/I) balance. However, the upstream factors triggering microglial activation remain unclear. Here, we identify gut-enriched Klebsiella pneumoniae ( K. pneumoniae ) in patients with epilepsy and demonstrate that its derived metabolites activate microglial inflammatory responses while inducing neuronal oxidative stress and apoptosis. In a mouse model combining intestinal colonization with K. pneumoniae and pentylenetetrazole (PTZ)-induced seizures, we show that this bacterium exacerbates seizure susceptibility, enhances neuroinflammation, and disrupts hippocampal E/I balance. Mechanistically, K. pneumoniae may promote epileptogenesis through metabolite-driven, TNF-dependent inflammatory signaling, leading to aberrant microglial activation. Collectively, these findings establish a mechanistic link between gut microbiota-derived metabolites and epilepsy and identify K. pneumoniae as a potential therapeutic target.

Source: Frontiers in Neuroscience

DOI: 10.3389/fnins.2026.1850015

Authors: Junqiang Li, Yan Wang, Weiwen Cai, Sirui Chen, Lan Zhang, Tiancheng Wang

Institutions: Lanzhou University Second Hospital, Lanzhou University

Language: English

Topic: Epilepsy research and treatment

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801