The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet

Olson, C. Anders; Vuong, Helen E.; Yano, Jessica M.; Liang, Qingxing Y.; Nusbaum, David J.; Hsiao, Elaine Y.

doi:10.1016/j.cell.2018.06.051

Cited by 215 publications

(247 citation statements)

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“…[10][11][12] Recent emerging evidence shows that gut microbiome changes were linked with onset of disorders including stroke, epilepsy, Parkinson's disease, depression, and schizophrenia via the "microbiota-gut-brain" (MGB) axis. [13][14][15][16][17] Thus it is becoming increasingly clear that the gut microbiome is a central regulator of host immune homeostasis, [9,18] whose dysregulation may participate in the onset of central (e.g., multiple sclerosis) and peripheral (e.g., rheumatoid arthritis) autoimmune diseases. [19,20] These findings compel us to determine whether MG, an immune-mediated disease of the NMJ, is accompanied by altered microbial composition and activity.…”

Section: Introductionmentioning

confidence: 99%

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome

Zheng

et al. 2019

Advanced Science

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Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. This work reports that MG is characterized by decreased α‐phylogenetic diversity, and significantly disturbed gut microbiome and fecal metabolome. The altered gut microbial composition is associated with fecal metabolome changes, with 38.75% of altered bacterial operational taxonomic units showing significant correlations with a range of metabolite biomarkers. Some microbes are particularly linked with MG severity. Moreover, a combination of microbial makers and their correlated metabolites enable discriminating MG from healthy controls (HCs) with 100% accuracy. To investigate whether disturbed gut mcirobiome might contribute to the onset of MG, germ‐free (GF) mice are initially colonized with MG microbiota (MMb) or healthy microbiota (HMb), and then immunized in a classic mouse model of MG. The MMb mice demonstrate substantially impaired locomotion ability compared with the HMb mice. This effect could be reversed by cocolonizing GF mice with both MMb and HMb. The MMb mice also exhibit similar disturbances of fecal metabolic pathways as found in MG. Together these data demonstrate disturbances in microbiome composition and activity that are likely to be relevant to the pathogenesis of MG.

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Section: Introductionmentioning

confidence: 99%

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome

Zheng

et al. 2019

Advanced Science

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“…The concept of the dysregulation of the gut‐brain axis implicates intestinal microbiota in depression, anxiety, schizophrenia, Alzheimer disease, autism, and Parkinson's disease . At the same time, explorations of the connection between dysbiosis and epilepsy remain limited, mostly focusing on microbiome as a target for ketogenic diet . Whether perturbations in gut microbiome can be linked directly to the epileptic process has not been studied, even though the nature of these perturbations suggests their relevance to epilepsy.…”

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confidence: 99%

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

et al. 2018

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SummaryThere has been growing interest in the role of intestinal microbiome in brain disorders. We examined whether dysbiosis can predispose to epilepsy. The study was performed in female and male Sprague‐Dawley rats. To induce dysbiosis, the rats were subjected to chronic restraint stress (two 2‐h long sessions per day, over 2 weeks). Cecal content from stressed and sham‐stressed donors was transplanted via oral gavage to recipients, in which commensal microbiota had been depleted by the antibiotics. The study included the following groups: (1) Sham stress, no microbiota transplant; (2) Stress, no microbiota transplant; (3) Sham‐stressed recipients transplanted with microbiota from sham‐stressed donors; (4) Stressed recipients transplanted with microbiota from sham‐stressed donors; (5) Sham‐stressed recipients transplanted with microbiota from stressed donors; and (6) Stressed recipients transplanted with microbiota from stressed donors. After microbiota transplant, all animals were subjected to kindling of the basolateral amygdala. Both chronic stress and microbiome transplanted from stressed to sham‐stressed subjects accelerated the progression and prolonged the duration of kindled seizures. Microbiome from sham‐stressed animals transplanted to chronically stressed rats, counteracted proepileptic effects of restraint stress. These findings directly implicate perturbations in the gut microbiome, particularly those associated with chronic stress, in the increased susceptibility to epilepsy.

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“…A wide range of environmental factors and neurological outcomes have been linked to altered microbial composition. The anti-seizure benefits of a ketogenic diet were found to be dependent upon the microbiome in mice [169]. Light-stress in mice led to enhanced abundances of some bacterial species and metabolites, which correlated with reduced memory potential [170].…”

Section: Environmental Exposures and The Microbiome-gut-brain Axismentioning

confidence: 99%

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

Hollander

Cory‐Slechta

Jacka

et al. 2020

Neuropsychopharmacol.

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The etiologic pathways leading to neuropsychiatric diseases remain poorly defined. As genomic technologies have advanced over the past several decades, considerable progress has been made linking neuropsychiatric disorders to genetic underpinnings. Interest and consideration of nongenetic risk factors (e.g., lead exposure and schizophrenia) have, in contrast, lagged behind heritable frameworks of explanation. Thus, the association of neuropsychiatric illness to environmental chemical exposure, and their potential interactions with genetic susceptibility, are largely unexplored. In this review, we describe emerging approaches for considering the impact of chemical risk factors acting alone and in concert with genetic risk, and point to the potential role of epigenetics in mediating exposure effects on transcription of genes implicated in mental disorders. We highlight recent examples of research in nongenetic risk factors in psychiatric disorders that point to potential shared biological mechanisms-synaptic dysfunction, immune alterations, and gut-brain interactions. We outline new tools and resources that can be harnessed for the study of environmental factors in psychiatric disorders. These tools, combined with emerging experimental evidence, suggest that there is a need to broadly incorporate environmental exposures in psychiatric research, with the ultimate goal of identifying modifiable risk factors and informing new treatment strategies for neuropsychiatric disease.

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The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet

Cited by 215 publications

References 0 publications

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome

Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome

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

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

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