Elsevier

Trends in Food Science & Technology

Volume 129, November 2022, Pages 581-590
Trends in Food Science & Technology

Plant-derived bioactive components regulate gut microbiota to prevent depression and depressive-related neurodegenerative diseases: Focus on neurotransmitters

https://doi.org/10.1016/j.tifs.2022.10.019Get rights and content

Highlights

  • The gut microbiota is closely related to brain development and function.

  • The microbiota-derived metabolites play crucial roles in gut-brain communication.

  • Dietary intervention may provide benefits by regulating the gut microbiota and releasing neuroactive metabolites.

Abstract

Background

Depression is a prevalent neuropsychiatric disorder that affects people all around the world. Alzheimer's disease (AD) and Parkinson's disease (PD) are two neurodegenerative diseases that are comorbid with depression behaviors. Mounting evidence reveals that gut microbiota is subject to brain activity and function. Therefore, targeting the gut microbiota may be a potential avenue to further the treatment and alleviate symptoms.

Scope and approach

Studies in animal models and clinical have determined that the gut microbiota can promote neurotransmitter production and transmission. Disturbance of neurotransmitters has long been thought to play a role in the etiology of neuropsychiatric disorders, but particular dietary intake can alter neurotransmitters by modulating the makeup of the gut microbiota and microbial metabolites, which speed up the treatment process. Therefore, we outline how neurotransmitters play a part in the major pathways related to the gut-brain axis (GBA). Additionally, the potential pathogenesis of the gut microbiota in AD and PD and the beneficial effects of plant-derived bioactive components are discussed.

Key findings and conclusions

In this article, we mainly focus on neurotransmitters derived from the microbiota of γ-aminobutyric acid (GABA), serotonin (5-HT), and dopamine and their effects on depression and neurodegenerative diseases via GBA. We discuss the dietary intervention of ingesting plant-derived active components such as polyphenols, polysaccharides, and peptides that may provide benefits by regulating the gut microbiota and releasing neurotransmitters/neuroactive metabolites, which provide a better understanding of dietary regulation to play part in anti-depressive and anti-degenerative processes.

Introduction

Depression, a prevalent psychiatric disorder, is marked by a high rate of incidence and relapse (Carlessi et al., 2021). It has been proposed that depression in later life may be an indication of latent neurodegeneration in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (Hurley & Tizabi, 2013). Conversely, outcomes of current medications and psychotherapies are suboptimal with common treatment failures. Although more than 1, 000 trials have been done, less than 20% of drug trials and less than 30% of therapy trials have a low risk of bias, and the question of real-life importance to people with depression has not been answered (Barandouzi et al., 2020). The persistent incapacity in treating depression is partly due to the lack of knowledge of molecular mechanisms underlying its onset. Therefore, efforts underway need to find effective approaches to understand depression's biological underpinnings to detect treatments to prevent or treat depression.

Amounting evidence indicates that the gut microbiota is a pivotal mediator in brain development and can bring about depression-like behavior by altering host metabolism. Gut microbiota did more than maintain homeostasis - it also regulated almost every major body system involving the central nervous system (CNS) (Cryan et al., 2020), which may impact the progress of neuropsychiatric diseases such as depression, and depression-related neurodegenerative diseases AD and PD by the gut-brain axis (GBA). The human intestinal microbiota is responsible for producing hundreds of metabolites that directly impact most systems and organs, including the intestinal epithelium, enteric nervous system (ENS), and brain (Needham et al., 2020). Numerous studies focus on microbiota neuroactive metabolic 5-hydroxytryptamine (5-HT)/serotonin, dopamine, noradrenaline, and γ-aminobutyric acid (GABA) derived from the gut microbiota to mediate depression through GBA, which may play an important role in the pathogenesis of depression and depressive behavior diseases. The relations for gut microbiota dysbiosis are manifold and varied, with several forces at play in it, but environmental factors especially diet and lifestyle changes can influence gut microbiota to a great extent. Growing evidence shows the importance of natural bioactive compounds in plants such as polyphenols, polysaccharides and peptides in the role of promoting mental and cognitive functions (Mizushige, 2021). These bacterial metabolite molecules cues conveyed from the gut microbiota to the brain can impact neurological function, immunological systems, emotions, and neurodegenerative disorders (Needham et al., 2020). From the standpoint of neurotransmitters throughout the GBA, we explain and explore how the gut microbiota plays a role in the pathogenesis of depression and depression-related neurodegenerative diseases including AD and PD. In addition, it is worth further studying that plant-derived bioactive components may provide benefits by regulating the gut microbiota and releasing neuroactive metabolites.

Section snippets

Neuromodulators between the microbiota and the brain

The GBA is a bi-directional communication channel that takes place both upstream and downstream pathways. Downstream pathways can initiate vagal efferent signaling and metabolic pathways by releasing neurotransmitters and hormones in the CNS. Neurotransmitters as endogenous chemical messengers, play a major role in the brain nerve network, as well as regulate intestinal secretion and motility in brain-to-gut signaling. Upstream pathways such as vagal and immune signaling are activated by gut

The gut microbiota in depression-related neurodegenerative diseases

The increasing aging population has prompted more research into the causes of age-related neurodegeneration, studies have led to discoveries that depression is a new hypothesis in the etiology of neurodegenerative processes (Hurley & Tizabi, 2013). AD and PD are two prevalent neurodegenerative diseases with cognitive deficits, psychiatric, and mood abnormalities, and are common comorbidity with depression (Galts et al., 2019). Depression accelerates the aging of the brain and increases the risk

Plant-derived bioactive components exert neuroprotective effects through GBA

Diet-induced gut microbiota imbalance can have some indirect influences on CNS. Obesity, for instance, generated by a high-fat diet is frequently accompanied by OS and inflammatory response, which is a risk factor for AD and PD. Obesity increases the Firmicutes/Bacteroidetes ratio of gut microbiota. This trend is also prevalent in neurodegeneration diseases, which may create an inflammatory milieu that promotes toxic misfolded protein aggregates (Chidambaram et al., 2022). The disturbance of

Conclusions

Recent years have witnessed a spurt of progress in the signal pathways from the gut to the brain and found that the microbial neuroprotective molecules released from gut microbiota can affect brain functions. In this review, we focus on the neurotransmitters GABA, 5-HT, and dopamine generated from the gut microbiota that may influence the progression of depression, AD, and PD through multiple routes. We also propose certain plant-derived components, such as polyphenols, polysaccharides, and

Declaration of competing interest

The authors have declared no conflict of interest.

Author contributions

Conceptualization, Writing-original draft——Z.S.; Supervision, Writing-original draft——L.C.; Writing-review and editing——Y.L. and S.Z.; Visualization——Z.W.; Supervision, Writing-review and editing——X.Z.All authors have read and agreed to the published version of the manuscript.

Acknowledgments

This research was funded by Zhejiang Provincial Key Research and Development Program (2020C02037) and Ningbo Natural Science Foundation (2021J107).

References (120)

  • C. Griñán-Ferré et al.

    The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer's disease pathology: From antioxidant to epigenetic therapy

    Ageing Research Reviews

    (2021)
  • S. Huang et al.

    Polysaccharides from Ganoderma lucidum promote cognitive function and neural progenitor proliferation in mouse model of Alzheimer's disease

    Stem Cell Reports

    (2017)
  • K.G. Jameson et al.

    Toward understanding microbiome-neuronal signaling

    Molecular Cell

    (2020)
  • R. Janik et al.

    Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate

    NeuroImage

    (2016)
  • G.A.R. Johnston

    Flavonoid nutraceuticals and ionotropic receptors for the inhibitory neurotransmitter GABA

    Neurochemistry International

    (2015)
  • J.R. Kelly et al.

    Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

    Brain, Behavior, and Immunity

    (2017)
  • L. Liang et al.

    Effects of gut microbiota disturbance induced in early life on the expression of extrasynaptic GABA-A receptor α5 and δ subunits in the hippocampus of adult rats

    Brain Research Bulletin

    (2017)
  • P. Liu et al.

    Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort

    Brain, Behavior, and Immunity

    (2019)
  • Q. Liu et al.

    Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis

    Brain, Behavior, and Immunity

    (2021)
  • H. Li et al.

    Ganoderma lucidum polysaccharides ameliorated depression-like behaviors in the chronic social defeat stress depression model via modulation of Dectin-1 and the innate immune system

    Brain Research Bulletin

    (2021)
  • T. Mizushige

    Neuromodulatory peptides: Orally active anxiolytic-like and antidepressant-like peptides derived from dietary plant proteins

    Peptides

    (2021)
  • Y. Sun et al.

    Polysaccharides confer benefits in immune regulation and multiple sclerosis by interacting with gut microbiota

    Food Research International

    (2021)
  • P. Tian et al.

    Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: A randomized clinical trial

    Brain, Behavior, and Immunity

    (2022)
  • P. Tian et al.

    Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice

    Neurobiology of Stress

    (2020)
  • M. Wang et al.

    Effect of oral and intraperitoneal administration of walnut-derived pentapeptide PW5 on cognitive impairments in APPSWE/PS1ΔE9 mice

    Free Radical Biology and Medicine

    (2022)
  • V.T.E. Aho et al.

    Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease

    Molecular Neurodegeneration

    (2021)
  • S. Askarova et al.

    The links between the gut microbiome, aging, modern lifestyle and Alzheimer's disease

    Frontiers in Cellular and Infection Microbiology

    (2020)
  • N. Ball et al.

    Parkinson's disease and the environment

    Frontiers in Neurology

    (2019)
  • Z.A. Barandouzi et al.

    Altered composition of gut microbiota in depression: A systematic review

    Frontiers in Psychiatry

    (2020)
  • T. Barichello et al.

    Sodium butyrate prevents memory impairment by re-establishing BDNF and GDNF expression in experimental pneumococcal meningitis

    Molecular Neurobiology

    (2015)
  • L. Bonfili et al.

    Microbiota modulation counteracts Alzheimer's disease progression influencing neuronal proteolysis and gut hormones plasma levels

    Scientific Reports

    (2017)
  • J.A. Bravo et al.

    Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

    Proceedings of the National Academy of Sciences of the United States of America

    (2011)
  • V. Cakova et al.

    Dendrobium: Sources of active ingredients to treat age-related pathologies

    Aging and Disease

    (2017)
  • A.S. Carlessi et al.

    Gut microbiota–brain axis in depression: The role of neuroinflammation

    European Journal of Neuroscience

    (2021)
  • G. Catalkaya et al.

    Interaction of dietary polyphenols and gut microbiota: Microbial metabolism of polyphenols, influence on the gut microbiota, and implications on host health

    Food Frontiers

    (2020)
  • M. Cheng et al.

    The interaction effect and mechanism between tea polyphenols and intestinal microbiota: Role in human health

    Journal of Food Biochemistry

    (2017)
  • Y. Chen et al.

    Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders

    Nutrients

    (2021)
  • A. Chudzik et al.

    Probiotics, prebiotics and postbiotics on mitigation of depression symptoms: Modulation of the brain–gut–microbiome axis

    Biomolecules

    (2021)
  • G. Clarke et al.

    The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner

    Molecular Psychiatry

    (2013)
  • S. Cogliati et al.

    Bacillus subtilis delays neurodegeneration and behavioral impairment in the Alzheimer's disease model Caenorhabditis elegans

    Journal of Alzheimer's Disease : JAD

    (2020)
  • A.S. Correia et al.

    Highlighting immune system and stress in major depressive disorder, Parkinson's, and Alzheimer's diseases, with a connection with serotonin

    International Journal of Molecular Sciences

    (2021)
  • E.B.M. Daliri et al.

    Bioactive peptides

    Foods

    (2017)
  • T.G. Dinan et al.

    Brain-gut-microbiota axis and mental health

    Psychosomatic Medicine

    (2017)
  • S. Donati Zeppa et al.

    Nutraceuticals and physical activity as antidepressants: The central role of the gut microbiota

    Antioxidants

    (2022)
  • Z. Dou et al.

    Neuroprotection of resveratrol against focal cerebral ischemia/reperfusion injury in mice through a mechanism targeting gut-brain axis

    Cellular and Molecular Neurobiology

    (2019)
  • S. Duranti et al.

    Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA

    Scientific Reports

    (2020)
  • S. Filosa et al.

    Polyphenols-gut microbiota interplay and brain neuromodulation

    Neural Regeneration Research

    (2018)
  • P.B. Gonçalves et al.

    Green tea epigallocatechin‐3‐gallate (EGCG) targeting protein misfolding in drug discovery for neurodegenerative diseases

    Biomolecules

    (2021)
  • C. González-Arancibia et al.

    Do your gut microbes affect your brain dopamine?

    Psychopharmacology

    (2019)
  • A.A. Grace

    Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression

    Nature Reviews Neuroscience

    (2016)
  • Cited by (3)

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