Influence of dietary supplementation with two distinct probiotic strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility and valproate response: Behavioral and biochemical studies in mice

IF 3.6 3区医学 Q2 NUTRITION & DIETETICS

Nutrition Pub Date : 2026-05-01 Epub Date: 2025-12-24 DOI:10.1016/j.nut.2025.113083

Piotr Wlaź DVM, PhD , Karolina Skonieczna-Żydecka PhD , Adrian Wiater PhD , Daniel Styburski PhD , Małgorzata Majewska PhD , Anna Boguszewska-Czubara MD, PhD , Elżbieta Wyska PhD , Alan González-Ibarra PhD , Nikola Gapińska MSc , Dorota Luchowska-Kocot MD, PhD , Renata Żelazowska MD, PhD , Marcin Grąz PhD , Katarzyna Socała PhD

{"title":"Influence of dietary supplementation with two distinct probiotic strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility and valproate response: Behavioral and biochemical studies in mice","authors":"Piotr Wlaź DVM, PhD , Karolina Skonieczna-Żydecka PhD , Adrian Wiater PhD , Daniel Styburski PhD , Małgorzata Majewska PhD , Anna Boguszewska-Czubara MD, PhD , Elżbieta Wyska PhD , Alan González-Ibarra PhD , Nikola Gapińska MSc , Dorota Luchowska-Kocot MD, PhD , Renata Żelazowska MD, PhD , Marcin Grąz PhD , Katarzyna Socała PhD","doi":"10.1016/j.nut.2025.113083","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Accumulating preclinical and clinical evidence suggests potential beneficial effects of probiotic supplementation in the management of epilepsy. Here, we aimed to investigate the effect of two distinct bacterial strains, <em>Bifidobacterium longum</em> R0175 and <em>Lacticaseibacillus rhamnosus</em> JB-1, on seizure susceptibility, the antiseizure efficacy of sodium valproate, behavioral and neurochemical parameters, and gut metabolomic profiles in mice.</div></div><div><h3>Methods</h3><div>Mice received daily oral administration of either <em>B. longum</em> R0175 or <em>L. rhamnosus</em> JB-1 for 28 d. Seizure thresholds were assessed using the maximal electroshock seizure threshold (MEST) test, the 6 Hz seizure threshold test, and the intravenous (<em>iv</em>) pentylenetetrazole (PTZ) seizure test. The efficacy of sodium valproate was evaluated in the subcutaneous (<em>sc</em>) PTZ seizure test. Additional assessments included anxiety-related behavior, neuromotor functions, brain neurochemical and inflammatory markers, fecal short-chain fatty acids (SCFAs), and untargeted metabolomic profiling of fecal samples.</div></div><div><h3>Results</h3><div><em>B. longum</em> R0175 and <em>L. rhamnosus</em> JB-1 did not affect the thresholds for tonic seizures in the MEST test and for psychomotor seizures in the 6 Hz test. <em>B. longum</em> R0175 slightly increased the threshold for myoclonic seizures in the <em>iv</em>PTZ. Both strains enhanced the antiseizure efficacy of sodium valproate without altering its serum or brain concentrations. No significant effects were observed on anxiety-related behavior, neuromotor function, neurochemical or inflammatory markers. Both probiotics increased the concentration of butyrate and total SCFAs in fecal samples. Metabolomic analysis revealed variations in the metabolism of bile acids, polyphenols, fatty acids, and amino acids.</div></div><div><h3>Conclusions</h3><div>The probiotics alone had minimal effects on seizure thresholds, but they enhanced the antiseizure efficacy of valproate, which may be linked to increased SCFA production and altered gut metabolism. These findings support further studies on probiotics as a complementary strategy in epilepsy treatment.</div></div>","PeriodicalId":19482,"journal":{"name":"Nutrition","volume":"145 ","pages":"Article 113083"},"PeriodicalIF":3.6000,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0899900725004009","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/12/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Accumulating preclinical and clinical evidence suggests potential beneficial effects of probiotic supplementation in the management of epilepsy. Here, we aimed to investigate the effect of two distinct bacterial strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility, the antiseizure efficacy of sodium valproate, behavioral and neurochemical parameters, and gut metabolomic profiles in mice.

Methods

Mice received daily oral administration of either B. longum R0175 or L. rhamnosus JB-1 for 28 d. Seizure thresholds were assessed using the maximal electroshock seizure threshold (MEST) test, the 6 Hz seizure threshold test, and the intravenous (iv) pentylenetetrazole (PTZ) seizure test. The efficacy of sodium valproate was evaluated in the subcutaneous (sc) PTZ seizure test. Additional assessments included anxiety-related behavior, neuromotor functions, brain neurochemical and inflammatory markers, fecal short-chain fatty acids (SCFAs), and untargeted metabolomic profiling of fecal samples.

Results

B. longum R0175 and L. rhamnosus JB-1 did not affect the thresholds for tonic seizures in the MEST test and for psychomotor seizures in the 6 Hz test. B. longum R0175 slightly increased the threshold for myoclonic seizures in the ivPTZ. Both strains enhanced the antiseizure efficacy of sodium valproate without altering its serum or brain concentrations. No significant effects were observed on anxiety-related behavior, neuromotor function, neurochemical or inflammatory markers. Both probiotics increased the concentration of butyrate and total SCFAs in fecal samples. Metabolomic analysis revealed variations in the metabolism of bile acids, polyphenols, fatty acids, and amino acids.

Conclusions

The probiotics alone had minimal effects on seizure thresholds, but they enhanced the antiseizure efficacy of valproate, which may be linked to increased SCFA production and altered gut metabolism. These findings support further studies on probiotics as a complementary strategy in epilepsy treatment.

查看原文本刊更多论文

日粮中添加两种不同的益生菌菌株：长双歧杆菌R0175和鼠李糖乳杆菌JB-1对小鼠癫痫易感性和丙戊酸反应的影响：行为和生化研究

目的越来越多的临床前和临床证据表明，补充益生菌对癫痫的治疗有潜在的有益作用。本研究旨在研究长双歧杆菌R0175和鼠李糖乳杆菌JB-1对小鼠癫痫易感性、丙戊酸钠的抗癫痫疗效、行为和神经化学参数以及肠道代谢组学特征的影响。方法小鼠每天口服长叶白刺R0175或鼠李糖L. JB-1 28 d。采用最大电休克发作阈值（MEST）试验、6 Hz发作阈值试验和静脉注射戊四唑（PTZ）发作试验评估癫痫发作阈值。丙戊酸钠在皮下（sc） PTZ癫痫发作试验中疗效评价。其他评估包括焦虑相关行为、神经运动功能、脑神经化学和炎症标志物、粪便短链脂肪酸（SCFAs）和粪便样本的非靶向代谢组学分析。长果R0175和鼠李糖JB-1对MEST测试中的强直性癫痫发作阈值和6hz测试中的精神运动性癫痫发作阈值没有影响。B. longum R0175轻微增加了ivPTZ肌阵挛性发作的阈值。两种菌株均增强丙戊酸钠的抗癫痫效果，但不改变其血清或脑浓度。在焦虑相关行为、神经运动功能、神经化学或炎症标志物方面未观察到显著影响。两种益生菌均增加了粪便样品中丁酸盐和总SCFAs的浓度。代谢组学分析揭示了胆汁酸、多酚、脂肪酸和氨基酸代谢的变化。结论单独使用益生菌对癫痫发作阈值的影响很小，但它们增强了丙戊酸的抗癫痫疗效，这可能与SCFA生成增加和肠道代谢改变有关。这些发现支持益生菌作为癫痫治疗补充策略的进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nutrition 医学-营养学

CiteScore

7.80

自引率

2.30%

发文量

300

审稿时长

60 days

期刊介绍： Nutrition has an open access mirror journal Nutrition: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Founded by Michael M. Meguid in the early 1980''s, Nutrition presents advances in nutrition research and science, informs its readers on new and advancing technologies and data in clinical nutrition practice, encourages the application of outcomes research and meta-analyses to problems in patient-related nutrition; and seeks to help clarify and set the research, policy and practice agenda for nutrition science to enhance human well-being in the years ahead.