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