Gut microbiota modulation by both Lactobacillus fermentum MSK 408 and ketogenic diet in a murine model of pentylenetetrazole-induced acute seizure

Abstract

Purpose: Seizures are a threat to the host brain and body and can even cause death in epileptic children. Ketogenic diet (KD) is suggested for children suffering from epileptic seizures and has been investigated for its anti-seizure effect. However, the relationships between KD and gut microbiota (GM) is not yet been deeply understood. Herein, we investigated the anti-seizure effect by administering KD and a lactic acid bacteria (LAB) in murine model of chemically induced seizures. We hypothesized that a single Lactobacillus fermentum MSK 408 (MSK 408) strain with or without KD may exert a neuroprotection by modulating host gut microbiota. Method: We performed animal study using pentylenetetrazole (PTZ) to induce seizure. Thirty 3-week-old male Institute of Cancer research (ICR) mice were divided in six groups, Normal diet (ND), ND + PTZ, ND + PTZ + LAB, KD, KD + PTZ, and KD + PTZ. Based on our previous study, 4:1 KD and selected MSK 408 strain was orally gavaged (4 x 10(9) CFU/mL) with both diets for 4 weeks. PTZ (40 mg/kg) was injected intraperitoneally 30 min before euthanization. Results: Compared to ND, KD significantly reduced the seizure frequency. Administration of MSK 408 with both ND and KD for 4 weeks restored serum lipid profile and tight junction protein mRNA expression of the gut and brain. Additionally, PCoA revealed that MSK 408 independently affected fecal short chain fatty acid (SCFA) content via gut microbiota (GM) modulation. PICRUSt suggested that the modulation of microbiota by KD and MSK 408 led to increased GABA (gamma-aminobutyric acid) metabolism. Significance: Our findings suggest that MSK 408 strain can be consumed with KD as supplement without interfering the anti-seizure action of KD, and may improve the serum lipid profile, and brain barrier function via gut microbiota and SCFA modulation.