Administration of Lactobacillus helveticus decreases the mortality caused by audiogenic seizures in DBA/1 mice

Objective

The research intended to probe the impact of probiotics (Pb) on seizure-induced respiratory arrest (S-IRA), gut flora, and 5‑hydroxytryptamine (5-HT) metabolism in a SUDEP model.

Methods

After priming and one month of normal diet feeding, 36 DBA/1 mice were randomly separated into the control and Pb groups to be provided with a normal diet only or a normal diet with added Lactobacillus helveticus (L. helveticus) respectively for three weeks. Then, audiogenic seizures (AGSz) and S‑IRA were tested from both groups. Ultra-high-pressure liquid chromatography (UHPLC) tested and 16S rRNA gene pyrosequencing were utilized to measure central and peripheral blood levels of serotonin-relative metabolism factors and microbiota.

Results

The rates of AGSz and S‑IRA both declined within the Pb group versus the control group. Pb treatment greatly enhanced gut bacterial relative abundances and richness. The comparative prosperity of Bacteroidetes, Saccharibacteria, and Actinobacteria was increased while Deferribacteres, Proteobacteria and Verrucomicrobia was decreased after Pb administration. The amount of 5‑HT and 5‑HIAA in the midbrain and 5‑HIAA in the telencephalon was raised in DBA/1 mice treated with Pb relative to the control.

Conclusion

Supplementation of L. helveticus is efficient in AGSz reduction and SUDEP protection. The elevation of 5‑HT and 5‑HIAA in the midbrain and 5‑HIAA levels in the telencephalon may be associated with SUDEP preservation. The considerable surge of Actinobacteria, Bacteroidetes and Saccharibacteria in intestinal microbiota seems to have a seizure/SUDEP-protective effect. The results support the premise that probiotics may be a candidate intervention to prevent SUDEP via its anti-convulsant effects.

Significance statement

These data provided evidence that the gut microbiota was implicated in the pathogenesis of SUDEP, probably related to its regulation of central 5‑HT system. Therefore we have reason to expect that probiotic be a candidate therapy for preventing SUDEP.

Graphic abstract