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

Background and Aims: 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...

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Autores principales:	Qiang Yue, Mingfei Cai, Bo Xiao, Qiong Zhan, Chang Zeng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SUDEP high-tryptophan diet 5-HT gut microbiota DBA/1 mice Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/94bd9f8cd8744db2acac519dfde71cba
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spelling	oai:doaj.org-article:94bd9f8cd8744db2acac519dfde71cba2021-11-30T13:44:04ZA High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice1664-229510.3389/fneur.2021.762323https://doaj.org/article/94bd9f8cd8744db2acac519dfde71cba2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.762323/fullhttps://doaj.org/toc/1664-2295Background and Aims: 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.Methods: 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 (n = 39) or HTD group (n = 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.Results: 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 Proteobacteria and Actinobacteria after HTD.Conclusions: 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 Proteobacteria and Actinobacteria may be related to the SUDEP-protective effect of HTD. Our findings shed light on a candidate choice of dietary prevention for SUDEP.Qiang YueMingfei CaiBo XiaoQiong ZhanChang ZengFrontiers Media S.A.articleSUDEPhigh-tryptophan diet5-HTgut microbiotaDBA/1 miceNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SUDEP high-tryptophan diet 5-HT gut microbiota DBA/1 mice Neurology. Diseases of the nervous system RC346-429
spellingShingle	SUDEP high-tryptophan diet 5-HT gut microbiota DBA/1 mice Neurology. Diseases of the nervous system RC346-429 Qiang Yue Mingfei Cai Bo Xiao Qiong Zhan Chang Zeng A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice
description	Background and Aims: 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.Methods: 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 (n = 39) or HTD group (n = 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.Results: 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 Proteobacteria and Actinobacteria after HTD.Conclusions: 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 Proteobacteria and Actinobacteria may be related to the SUDEP-protective effect of HTD. Our findings shed light on a candidate choice of dietary prevention for SUDEP.
format	article
author	Qiang Yue Mingfei Cai Bo Xiao Qiong Zhan Chang Zeng
author_facet	Qiang Yue Mingfei Cai Bo Xiao Qiong Zhan Chang Zeng
author_sort	Qiang Yue
title	A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice
title_short	A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice
title_full	A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice
title_fullStr	A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice
title_full_unstemmed	A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice
title_sort	high-tryptophan diet reduces seizure-induced respiratory arrest and alters the gut microbiota in dba/1 mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/94bd9f8cd8744db2acac519dfde71cba
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A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

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