AUTHOR=Yue Qiang , Cai Mingfei , Xiao Bo , Zhan Qiong , Zeng Chang 

TITLE=A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

JOURNAL=Frontiers in Neurology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.762323

DOI=10.3389/fneur.2021.762323

ISSN=1664-2295

ABSTRACT=<p><bold>Background and Aims:</bold> Central 5-hydroxytryptamine (5-HT) defects are responsible for the occurrence of sudden unexpected death in epilepsy (SUDEP). The DBA/1 mouse is an animal model of SUDEP since the mouse exhibits audiogenic seizure-induced respiratory arrest (S-IRA). The synthesis of central 5-HT is closely related to the gut microbiota. Moreover, emerging studies suggest a possible role for the microbiota in mitigating seizure likelihood. Based on this, we aimed to explore the effect of a high-tryptophan diet (HTD) on SUDEP as well as the synthesis and metabolism of central 5-HT. Furthermore, we investigated the involvement of the gut microbiota in this process.</p><p><bold>Methods:</bold> All DBA/1 mice were subjected to acoustic stimulation to induce seizures. Only those mice that exhibited S-IRA were randomly assigned to the normal diet (ND) group (<italic>n</italic> = 39) or HTD group (<italic>n</italic> = 53). After 1 month of dietary intervention, (1) S-IRA rates were evaluated, (2) the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the plasma and brain were determined by ultra-high-pressure liquid chromatography, and (3) the fecal flora biodiversity and species composition were analyzed by 16S rDNA microbiota profiling.</p><p><bold>Results:</bold> The S-IRA rate in DBA/1 mice was significantly reduced in the HTD group compared with that in the control group. HTD increased the levels of 5-HT and 5-HIAA in both the telencephalon and midbrain. HTD significantly elevated the species richness and diversity of the gut microbiota. Moreover, there was a significant difference in the gut microbiota composition between the two groups, and the intestinal flora was dominated by <italic>Proteobacteria</italic> and <italic>Actinobacteria</italic> after HTD.</p><p><bold>Conclusions:</bold> HTD is efficient in lowering S-IRA rates and elevating the central 5-HT level in DBA/1 mice. The gut microbiota was altered after HTD intervention. The significant increase in <italic>Proteobacteria</italic> and <italic>Actinobacteria</italic> may be related to the SUDEP-protective effect of HTD. Our findings shed light on a candidate choice of dietary prevention for SUDEP.</p>