Gut Microbiota, the Ketogenic Diet and Epilepsy

Spinelli, Egidio; Blackford, Robyn

doi:10.15844/pedneurbriefs-32-10

Cited by 20 publications

(19 citation statements)

References 4 publications

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“…In general, increases in Firmicutes and Actinobacteria are seen in KD-responding children. Although, increases in Alistipes and Ruminococcaceae are apparent in nonresponders [319]. Similar patterns have been reported by authors investigating KD effects in animal models of epilepsy, with a positive effect being associated with changes in the composition of the microbiota associated with relative increases in levels of Akkermansia and Parabacteroides [231].…”

Section: Caveats and Uncertaintysupporting

confidence: 81%

“…Although the data reviewed above suggest that BHB entry into the brain is a major driver of the therapeutic benefits of the KD or of KB supplements, it should be emphasized that other factors may be involved and the mechanisms underpinning such therapeutic benefits are not completely understood either in the case of epilepsy or otherwise. For example, several authors have reported profound changes in the composition of the microbiota following the administration of a KD in children with intractable epilepsy, which appear to be important if not essential for seizure control [231,319,320]. In general, increases in Firmicutes and Actinobacteria are seen in KD-responding children.…”

Section: Caveats and Uncertaintymentioning

confidence: 99%

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Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

et al. 2020

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Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson’s disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurodegenerative and neuroprogressive disorders, there are detrimental effects of oxidative stress, mitochondrial dysfunction, and neuroinflammation on neuronal function. However, they also adversely impact on neurone–glia interactions, disrupting the role of microglia and astrocytes in central nervous system (CNS) homeostasis. Astrocytes are the main site of CNS fatty acid oxidation; the resulting ketone bodies constitute an important source of oxidative fuel for neurones in an environment of glucose restriction. Importantly, the lactate shuttle between astrocytes and neurones is dependent on glycogenolysis and glycolysis, resulting from the fact that the astrocytic filopodia responsible for lactate release are too narrow to accommodate mitochondria. The entry into the CNS of ketone bodies and fatty acids, as a result of nutritional ketosis, has effects on the astrocytic glutamate–glutamine cycle, glutamate synthase activity, and on the function of vesicular glutamate transporters, EAAT, Na+, K+-ATPase, Kir4.1, aquaporin-4, Cx34 and KATP channels, as well as on astrogliosis. These mechanisms are detailed and it is suggested that they would tend to mitigate the changes seen in many neurodegenerative and neuroprogressive disorders. Hence, it is hypothesized that nutritional ketosis may have therapeutic applications in such disorders.

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Section: Caveats and Uncertaintysupporting

confidence: 81%

Section: Caveats and Uncertaintymentioning

confidence: 99%

Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

et al. 2020

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“…In fact, mouse models of refractory epilepsy showed that those given antibiotics or reared in a germ-free environment were resistant to seizure protection from KD, while keto microbiota fecal transplant helped mice with seizure control. Therefore, these results support that keto microbiota is necessary to protect against seizures [32,40].…”

Section: Ketogenic Diet Keto Microbiota and Epilepsysupporting

confidence: 70%

“…However, little is known about the underlying mechanisms of action of KD. The most accepted hypotheses point out: metabolic changes, alteration of the signalling pathways, changes in the production of hormones and neurotransmitters, epigenetic modifications [22,24,27], and as would be expected, modulation of the microbiota [32].…”

Section: Modulation Of the Gut Microbiota Profilementioning

confidence: 99%

“…Interestingly, after a KD intervention, patients were differentiated into responder or non-responder subjects according to their gut microbiota changes, suggesting that the effectiveness of a KD was driven by the gut microbiota [5,32]. Moreover, responder and non-responder groups differed in gut bacteria profiles at the level of order, family and genus, but also in microbial metabolites production.…”

Section: Ketogenic Diet Keto Microbiota and Epilepsymentioning

confidence: 99%

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Keto microbiota: A powerful contributor to host disease recovery

Cabrera-Mulero

Tinahones

Bandera

et al. 2019

Rev Endocr Metab Disord

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Gut microbiota (GM) is a key contributor to host metabolism and physiology. Data generated on comparing diseased and healthy subjects have reported changes in the GM profile between both health states, suggesting certain bacterial composition could be involved in pathogenesis. Moreover, studies reported that reshaping of GM could contribute actively to disease recovery. Interestingly, ketogenic diets (KD) have emerged recently as new economic dietotherapeutic strategy to combat a myriad of diseases (refractory epilepsy, obesity, cancer, neurodegenerative diseases…). KD, understood in a broad sense, refers to whatever dietetic approximation, which causes physiological ketosis. Therefore, high fat-low carbs diets, fasting periods or caloric restriction constitute different strategies to produce an increase of main ketones bodies, acetoacetate and β-hydroxybutyrate, in blood. Involved biological mechanisms in ketotherapeutic effects are still to be unravelled. However, it has been pointed out that GM remodelling by KD, from now on "keto microbiota", may play a crucial role in patient response to KD treatment. In fact, germfree animals were resistant to ketotherapeutic effects; reinforcing keto microbiota may be a powerful contributor to host disease recovery. In this review, we will comment the influence of gut microbiota on host, as well as, therapeutic potential of ketogenic diets and keto microbiota to restore health status. Current progress and limitations will be argued too. In spite of few studies have defined applicability and mechanisms of KD, in the light of results, keto microbiota might be a new useful therapeutic agent.

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