Transcutaneous vagus nerve stimulation: a new strategy for Alzheimer’s disease intervention through the brain-gut-microbiota axis?

Yan, Long; Li, Hong; Qian, Yulin; Zhang, Junfeng; Cong, Shan; Zhang, Xuemin; Wu, Linna; Wang, Yu; Wang, Meng; Yu, Tao

doi:10.3389/fnagi.2024.1334887

Cited by 8 publications

(3 citation statements)

References 149 publications

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“…diabetes, depression and neurodegenerative diseases 65 – 72 . In addition, long-term stress linked to impacted intestinal permeability and changes on the microbiome and concequently interfere with psychiatric phenotypes and medication 65 – 69 , leading us to conjecture that the oral microbiome is equally capable of promoting such interactions.…”

Section: Discussionmentioning

confidence: 99%

The oral microbiome is associated with HPA axis response to a psychosocial stressor

Charalambous,

Mériaux,

Guebels

et al. 2024

Sci Rep

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Intense psychosocial stress during early life has a detrimental effect on health-disease balance in later life. Simultaneously, despite its sensitivity to stress, the developing microbiome contributes to long-term health. Following stress exposure, HPA-axis activation regulates the “fight or flight” response with the release of glucose and cortisol. Here, we investigated the interaction between the oral microbiome and the stress response. We used a cohort of 115 adults, mean age 24, who either experienced institutionalisation and adoption (n = 40) or were non-adopted controls (n = 75). Glucose and cortisol measurements were taken from participants following an extended socially evaluated cold pressor test (seCPT) at multiple time points. The cohort´s oral microbiome was profiled via 16S-V4 sequencing on microbial DNA from saliva and buccal samples. Using mixed-effect linear regressions, we identified 12 genera that exhibited an interaction with host’s cortisol-glucose response to stress, strongly influencing intensity and clearance of cortisol and glucose following stress exposure. Particularly, the identified taxa influenced the glucose and cortisol release profiles and kinetics following seCPT exposure. In conclusion, our study provided evidence for the oral microbiome modifying the effect of stress on the HPA-axis and human metabolism, as shown in glucose-cortisol time series data.

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Section: Discussionmentioning

confidence: 99%

The oral microbiome is associated with HPA axis response to a psychosocial stressor

Charalambous,

Mériaux,

Guebels

et al. 2024

Sci Rep

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“…Aside from ACh and mitochondrial import, the lost γ oscillations may be restored by entrainment with sensory stimuli, such as ultrasound or transcutaneous vagal nerve stimulation (tVNS) at 40 Hz, emphasizing a potential strategy for SCZ and SLDs [149,153]. Interestingly, tVNS improves not only the neuronal function but also optimizes gut permeability, decreasing microbial translocation [149,154].…”

Section: Entrainment Of Gamma Band Oscillations In Schizophreniamentioning

confidence: 99%

The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes

Sfera,

Imran,

Sfera

et al. 2024

Preprint

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For the past 70 years, dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling, antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there was limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal, senescence, brain volume loss, attenuation of gamma oscillations on electroencephalogram and oxidation of lipids in plasma and mitochondrial membranes. We surmise that aberrant activation of aryl hydrocarbon receptor by toxins derived from the gut microbes or the environment drives premature cellular, including neuronal, senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation. The aim of this narrative review is twofold: 1. To summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders. 2. To discuss novel strategies for improving long-term outcome in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor.

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“…It is currently established that severe mental illness is associated with cellular/neuronal senescence, indicating that endogenous or exogenous toxins may play a key role in this pathology [ 155 , 156 , 157 ]. For example, viral or bacterial infections induce premature aging in brain cells by eliciting immune responses, likely triggering psychosis [ 158 , 159 ].…”

Section: Senotherapeuticsmentioning

confidence: 99%

Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes

Sfera,

Imran,

Sfera

et al. 2024

IJMS

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For the past 70 years, the dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling and antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there has been limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal senescence, brain volume loss, the attenuation of gamma oscillations in electroencephalograms, and the oxidation of lipids in the plasma and mitochondrial membranes. We surmise that the aberrant activation of the aryl hydrocarbon receptor by toxins derived from gut microbes or the environment drives premature cellular and neuronal senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including the impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation. The aim of this narrative review is twofold: (1) to summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders, and (2) to discuss novel strategies for improving long-term outcomes in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor antagonists.

show abstract

Transcutaneous vagus nerve stimulation: a new strategy for Alzheimer’s disease intervention through the brain-gut-microbiota axis?

Cited by 8 publications

References 149 publications

The oral microbiome is associated with HPA axis response to a psychosocial stressor

The oral microbiome is associated with HPA axis response to a psychosocial stressor

The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes

Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes

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