Ketogenic Diet Modulates Neuroinflammation via Metabolites from Lactobacillus reuteri After Repetitive Mild Traumatic Brain Injury in Adolescent Mice

Dilimulati, Dilirebati; Zhang, Fengchen; Shao, Shuai; Lv, Tao; Lu, Qinghui; Cao, Mengqiu; Jin, Yichao; Feng, Jia; Zhang, Xiaohua

doi:10.1007/s10571-022-01226-3

Cited by 11 publications

(7 citation statements)

References 51 publications

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“…Although Lactobacillus was known as one of the proverbial probiotics with an anti‐inflammatory effect, the concentration of Lactobacillus was elevated in PD patients 12,51 . KD treatment effectively decreased the level of Lactobacillus in agreement with previous studies, indicating more in‐depth studies were required to investigate the relationship among Lactobacillus , KD, and PD progression 52,53 . Intriguingly, we found an increase of Citrobacter in MPTP‐induced mice and the relative abundance of Citrobacter was reduced after the KD treatment.…”

Section: Discussionsupporting

confidence: 88%

Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites

Jiang,

Wang,

Zhang

et al. 2023

MedComm

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The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics.We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research isThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionsupporting

confidence: 88%

Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites

Jiang,

Wang,

Zhang

et al. 2023

MedComm

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“…They are thus at risk of repeated brain concussion episodes, which soon lead to chronic post-traumatic encephalopathy. Extremely important is the fact that in the situation of brain trauma and energetic collapse, the number of MCT channels (which transport ketone bodies to cells) in the brain cells increases by 85%; the number of β-hydroxybutyrate-metabolising enzymes also increases [ 37 , 38 , 39 , 40 , 41 , 42 ]. Based on that, we can say that the brain demands another source of energy, which can be provided by ketone bodies.…”

Section: The Range and Mechanisms Of The Ketogenic Diet Effect In Neu...mentioning

confidence: 99%

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

2022

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Over a hundred years of study on the favourable effect of ketogenic diets in the treatment of epilepsy have contributed to a long-lasting discussion on its potential influence on other neurological diseases. A significant increase in the number of scientific studies in that field has been currently observed. The aim of this paper is a widespread, thorough analysis of the available scientific evidence in respect of the role of the ketogenic diet in the therapy of neurological diseases such as: epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A wide range of the mechanisms of action of the ketogenic diet has been demonstrated in neurological diseases, including, among other effects, its influence on the reduction in inflammatory conditions and the amount of reactive oxygen species (ROS), the restoration of the myelin sheath of the neurons, the formation and regeneration of mitochondria, neuronal metabolism, the provision of an alternative source of energy for neurons (ketone bodies), the reduction in glucose and insulin concentrations, the reduction in amyloid plaques, the induction of autophagy, the alleviation of microglia activation, the reduction in excessive neuronal activation, the modulation of intestinal microbiota, the expression of genes, dopamine production and the increase in glutamine conversion into GABA. The studies discussed (including randomised controlled studies), conducted in neurological patients, have stressed the effectiveness of the ketogenic diet in the treatment of epilepsy and have demonstrated its promising therapeutic potential in Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A frequent advantage of the diet was demonstrated over non-ketogenic diets (in the control groups) in the therapy of neurological diseases, with simultaneous safety and feasibility when conducting the nutritional model.

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Section: Discussionmentioning

confidence: 99%

“…Additionally, a more recent study discovered that the KD alters neuroinflammation in mice with repetitive mild traumatic brain injury (rMTBI) via metabolites from the gut microbe Lactobacillus reuteri [ 81 ]. In these mice, treatment reduced microgliosis and neuroinflammation while improving neurological function [ 81 ]. This has enormous potential application for BHB’s ability to modulate the general gut microbiome and reduce inflammation in people with neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative Processes in Neurological Diseases: A Scoping Review

2023

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This scoping review aimed to summarise the effects of the ketone body β-hydroxybutyrate. The review details the revealed pathways and functional properties following its intervention in the context of neurodegenerative diseases. In this study, 5 research publications that met the inclusion and exclusion criteria were shortlisted. Following the intervention, we discovered a tendency of reduced inflammatory status in microglia, as evidenced by lower levels of pro-inflammatory mediators produced, reduced microgliosis in afflicted tissues, and enhanced cognitive functions in neurodegenerative models. We found that there is a significant overlap in the mechanism of action of b-hydroxybutyrate (BHB) via activation of the G-protein-Coupled Receptor 109A (GPR109a) receptor and deactivation of the inflammasome complex. Furthermore, although comparing outcomes can be challenging due to the heterogeneity in the study model, the results we have assembled here were consistent, giving us confidence in the intervention’s efficacy. We also discussed new studies where BHB is involved in various roles in regulating inflammation in microglia, allowing for fresh therapeutic targets against neurodegeneration. This brief review provides evidence to support the huge potential of BHB in the treatment of neurodegenerative illnesses.

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Ketogenic Diet Modulates Neuroinflammation via Metabolites from Lactobacillus reuteri After Repetitive Mild Traumatic Brain Injury in Adolescent Mice

Cited by 11 publications

References 51 publications

Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites

Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative Processes in Neurological Diseases: A Scoping Review

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