Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome

Medel-Matus, Jesús-Servando; Shin, Don; Dorfman, Edward; Sankar, Raman; Mazarati, Andréy

doi:10.1002/epi4.12114

Cited by 67 publications

(75 citation statements)

References 35 publications

(40 reference statements)

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“…22 Seizure susceptibility could be transferred by fecal microbial transplants (FMTs) in rats. 23 This finding was supported by a single case study where a patient became seizure-free for at least 20 months after an FMT for Crohn’s disease. 24…”

Section: Discussionmentioning

confidence: 74%

The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy

Lindefeldt

Eng

Darban

et al. 2019

npj Biofilms Microbiomes

180

165

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The gut microbiota has been linked to various neurological disorders via the gut–brain axis. Diet influences the composition of the gut microbiota. The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet established for treatment of therapy-resistant epilepsy in children. Its efficacy in reducing seizures has been confirmed, but the mechanisms remain elusive. The diet has also shown positive effects in a wide range of other diseases, including Alzheimer’s, depression, autism, cancer, and type 2 diabetes. We collected fecal samples from 12 children with therapy-resistant epilepsy before starting KD and after 3 months on the diet. Parents did not start KD and served as diet controls. Applying shotgun metagenomic DNA sequencing, both taxonomic and functional profiles were established. Here we report that alpha diversity is not changed significantly during the diet, but differences in both taxonomic and functional composition are detected. Relative abundance of bifidobacteria as well as E. rectale and Dialister is significantly diminished during the intervention. An increase in relative abundance of E. coli is observed on KD. Functional analysis revealed changes in 29 SEED subsystems including the reduction of seven pathways involved in carbohydrate metabolism. Decomposition of these shifts indicates that bifidobacteria and Escherichia are important contributors to the observed functional shifts. As relative abundance of health-promoting, fiber-consuming bacteria becomes less abundant during KD, we raise concern about the effects of the diet on the gut microbiota and overall health. Further studies need to investigate whether these changes are necessary for the therapeutic effect of KD.

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Section: Discussionmentioning

confidence: 74%

The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy

Lindefeldt

Eng

Darban

et al. 2019

npj Biofilms Microbiomes

180

165

View full text Add to dashboard Cite

show abstract

“…This means that removing the natural intestinal flora can subsequently eliminate the effects of beneficial bacteria. For example, Jesus-Servando et al showed that chronic stress can facilitate epilepsy in an animal model by altering the gut microbial profile [40]. Xie et al reported that ketogenic diets alter intestinal microbiome in resistant epileptic children [41].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Intestinal Natural Micro Flora Removal on Susceptibility to Have Seizure in Male Wistar Rats

et al. 2020

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Background and Aim: Epilepsy is a common brain disorder. Brain function can be affected by the intestinal microflora. The intestinal microflora have a major role in modulating immune responses, producing essential metabolites and mediating neurotransmitters. Antibiotics can affect and reduce these roles and functions by eliminating the intestinal microflora. The aim of this study was to investigate the effect of intestinal natural micro flora removal on seizure susceptibility and seizure behavior modification with the use of probiotics in male Wistar rats. Methods & Materials: This study was performed on 32 male Wistar rats with weight range 200-250 gr. The animals were randomly divided into four groups: 1. Control group; 2. Antibiotic group; 3. Probiotic group and 4. Antibiotic + probiotic group. To remove the microflora, antibiotics (neomycin, ampicillin, and metronidazole) for three weeks and for replacement of microflora, probiotics (Lactobacilli casei, Lactobacillus acidophilus and Bifidobacterium bifidum) for four weeks were administered. Seizures were performed by intraperitoneal injection of pentylentrazole. The microflora was examined by the MRS Agar medium and the Pure Plate method. The data were statistically analyzed in Graph Pad Prism V. 8. Ethical Considerations: This study was approved by the Research Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1395.176). Results: The use of antibiotics lead to decrease the number of intestinal bacteria (P<0.0001), increased the severity and stability of seizure stages (P<0.05) and decreased the time delay of seizure onset (P<0.05) compared to the control group. Probiotic consumption by modifying the intestinal microflora (P<0.0001) reduced the severity of seizure and increased the time delay of seizure onset (P<0.05). Conclusion: Elimination of microflora has the potential to induce seizures, which can be compensated by administration of probiotics.

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“…Using the NISS, daily stress exposure Furthermore, the estimates indicate that if these genera are present, infants with higher stress exposure tend to have higher relative abundances of Proteus and Veillonella. In the animal model, stress has been linked to bowel disease (Chow, Tang, & Mazmanian, 2011;Medel-Matus, Shin, Dorfman, Sankar, & Mazarati, 2018;Reber et al, 2016). Additionally, the presence of Proteobacteria pathobionts species has been shown to profoundly influence vulnerability to gut pathology (Chow et al, 2011;Langgartner et al, 2017).…”

Section: Re Sultsmentioning

confidence: 99%

Effects of early life NICU stress on the developing gut microbiome

D'Agata

Welandawe

et al. 2019

Developmental Psychobiology

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Succession of gut microbial community structure for newborns is highly influenced by early life factors. Many preterm infants cared for in the NICU are exposed to parent–infant separation, stress, and pain from medical care procedures. The purpose of the study was to investigate the impact of early life stress on the trajectory of gut microbial structure. Stool samples from very preterm infants were collected weekly for 6 weeks. NICU stress exposure data were collected daily for 6 weeks. V4 region of the 16S rRNA gene was amplified by PCR and sequenced. Zero‐inflated beta regression model with random effects was used to assess the impact of stress on gut microbiome trajectories. Week of sampling was significant for Escherichia, Staphylococcus, Enterococcus, Bifidobacterium, Proteus, Streptococcus, Clostridium butyricum, and Clostridium perfringens. Antibiotic usage was significant for Proteus, Citrobacter, and C. perfringens. Gender was significant for Proteus. Stress exposure occurring 1 and 2 weeks prior to sampling had a significant effect on Proteus and Veillonella. NICU stress exposure had a significant effect on Proteus and Veillonella. An overall dominance of Gammaproteobacteria was found. Findings suggest early life NICU stress may significantly influence the developing gut microbiome, which is important to NICU practice and future microbiome research.

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Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome

Cited by 67 publications

References 35 publications

The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy

The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy

The Effect of Intestinal Natural Micro Flora Removal on Susceptibility to Have Seizure in Male Wistar Rats

Effects of early life NICU stress on the developing gut microbiome

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