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Modulation of Microbiota-Gut-Brain Axis in the Disorders of Brain and Mind

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 21648

Special Issue Editors

Independent Researcher, New York, NY 10021, USA
Interests: neurological diseases; pathophysiology; therapeutics; animal models; molecular mechanisms; drug development; mitochondria; biomarker; posttranslational modification; transcription factor; gut-brain axis; Huntington’s disease; Parkinson’s disease; Alzheimer’s disease
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Guest Editor
Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
Interests: antimicrobial packaging; antimicrobial activity; edible films; biofilms; bioactive compounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite its conceptualization in the 18th century, the microbiota-gut-brain research went into a temporary hiatus for a while and was largely sidelined until it was thrust back into action with the realization of the “second brain” theory in the late 1990s. Presently, the bidirectional communications that span through the central nervous system (brain and spinal cord), the autonomic nervous system, the enteric nervous system and the hypothalamic-pituitary-adrenal axis through neuroimmune, neuroendocrine, and direct neural pathways such as the vagus nerve, are often referred to as the microbiota-gut-brain axis. Aging, high fat/low fiber diet, life-style related factors, such as stress, obesity, sedentary living etc. as well as certain infections alter the normal balance of gut microbiota resulting in dysbiosis. Dysbiosis is further thought to increase the permeability of intestinal epithelial barrier, promoting invasion of different bacteria, viruses, and their neuroactive products that support neuroinflammatory reactions in the brain, produce blood-brain barrier dysfunction and induce systemic inflammation. More recently, gut microbiota dysbiosis is considered to be a contributing factor in the disorders of brain and mind, namely, neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), and psychiatric disorders including schizophrenia, bipolar disorder, autism, dementia, depression and anxiety. The modulation of gut microbiota through personalized diet, oral bacteriotherapy including prebiotics, medicinal herbs, probiotics, and synbiotics have opened new vistas for exploration of potential therapeutic opportunities. With our special issue, we hope to bring to fore the recent progress made in the elucidation of mechanisms of this ‘central connection’ and targeted therapeutic modulation of the microbiota-gut-brain axis in the context of neurodegenerative diseases and psychiatric disorders.

Topics of this special issue include, but are not limited to:

  • Modulation of gut-brain axis in neurodegeneration: mechanisms and potential therapeutic interventions;
  • Contribution of dysbiosis to the development of Alzheimer’s disease pathologies and cognitive impairment;
  • Gut microbiome and Parkinson’s disease;
  • Role of microbiota-gut-brain axis in management of mental health disorders such as depression, anxiety, bipolar disorder, post-traumatic stress disorder (PTSD), schizophrenia;
  • Therapeutic benefits of a healthy gut to reduce systemic inflammation for a healthy brain and mind.

Dr. Ashu Johri
Prof. Dr. Dan Cristian Vodnar
Guest Editors

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Keywords

  • neurodegeneration
  • Parkinson’s disease
  • Alzheimer’s disease
  • mood disorders
  • psychiatric disorders
  • intestinal flora
  • dysbiosis
  • gut-brain axis
  • therapeutics

Published Papers (6 papers)

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Research

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12 pages, 1235 KiB  
Article
Gut Microbiota and Brain Alterations after Refeeding in a Translational Anorexia Nervosa Rat Model
by Stefanie Trinh, Vanessa Kogel, Lilly Kneisel, Elena Müller-Limberger, Beate Herpertz-Dahlmann, Cordian Beyer and Jochen Seitz
Int. J. Mol. Sci. 2023, 24(11), 9496; https://doi.org/10.3390/ijms24119496 - 30 May 2023
Cited by 3 | Viewed by 1366
Abstract
The gut microbiota composition is causally involved in the regulation of body weight. Through the gut–brain axis, microbiota play a role in psychiatric disorders including anorexia nervosa (AN). Previously, we showed microbiome changes to be associated with brain volume and astrocyte reductions after [...] Read more.
The gut microbiota composition is causally involved in the regulation of body weight. Through the gut–brain axis, microbiota play a role in psychiatric disorders including anorexia nervosa (AN). Previously, we showed microbiome changes to be associated with brain volume and astrocyte reductions after chronic starvation in an AN animal model. Here, we analyzed whether these alterations are reversible after refeeding. The activity-based anorexia (ABA) model is a well-established animal model that mimics several symptoms of AN. Fecal samples and the brain were analyzed. Like previous results, significant alterations in the microbiome were observed after starvation. After refeeding, including the normalization of food intake and body weight, α- and β-diversity, as well as the relative abundance of specific genera, were largely normalized in starved rats. Brain parameters appeared to normalize alongside microbial restitution with some aberrations in the white matter. We confirmed our previous findings of microbial dysbiosis during starvation and showed a high degree of reversibility. Thus, microbiome alterations in the ABA model appear to be mostly starvation-related. These findings support the usefulness of the ABA model in investigating starvation-induced effects on the microbiota–gut–brain axis to help comprehend the pathomechanisms of AN and potentially develop microbiome-targeted treatments for patients. Full article
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19 pages, 3422 KiB  
Article
Neuroprotective Effects of Lactobacillus plantarum PS128 in a Mouse Model of Parkinson’s Disease: The Role of Gut Microbiota and MicroRNAs
by Yan Zhang Lee, Shih-Hsuan Cheng, Min-Yu Chang, Yu-Fen Lin, Chien-Chen Wu and Ying-Chieh Tsai
Int. J. Mol. Sci. 2023, 24(7), 6794; https://doi.org/10.3390/ijms24076794 - 5 Apr 2023
Cited by 11 | Viewed by 4384
Abstract
Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced PD mouse model, we observed that administration of Lactobacillus plantarum PS128 (PS128) significantly improved motor deficits in PD-like mice, accompanied by an increased level of dopamine, reduced dopaminergic neuron loss, reduced microglial activation, reduced levels of inflammatory factors, and enhanced expression of neurotrophic factor in the brain. Notably, the inflammation-related expression of miR-155-5p was significantly upregulated in the proximal colon, midbrain, and striatum of PD-like mice. PS128 reduced the level of miR-155-5p, whereas it increased the expression of suppressor of cytokine signaling 1 (SOCS1), a direct target of miR-155-5p and a critical inhibitor of the inflammatory response in the brain. Alteration of the fecal microbiota in PD-like mice was partially restored by PS128 administration. Among them, Bifidobacterium, Ruminiclostridium_6, Bacteroides, and Alistipes were statistically correlated with the improvement of rotenone-induced motor deficits and the expression of miR-155-5p and SOCS1. Our findings suggested that PS128 ameliorates motor deficits and exerts neuroprotective effects by regulating the gut microbiota and miR-155-5p/SOCS1 pathway in rotenone-induced PD-like mice. Full article
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22 pages, 1647 KiB  
Article
Mycobacterium vaccae NCTC 11659, a Soil-Derived Bacterium with Stress Resilience Properties, Modulates the Proinflammatory Effects of LPS in Macrophages
by Evan M. Holbrook, Cristian A. Zambrano, Caelan T. O. Wright, Elizabeth M. Dubé, Jessica R. Stewart, William J. Sanders, Matthew G. Frank, Andrew S. MacDonald, Stefan O. Reber and Christopher A. Lowry
Int. J. Mol. Sci. 2023, 24(6), 5176; https://doi.org/10.3390/ijms24065176 - 8 Mar 2023
Cited by 1 | Viewed by 2424
Abstract
Inflammatory conditions, including allergic asthma and conditions in which chronic low-grade inflammation is a risk factor, such as stress-related psychiatric disorders, are prevalent and are a significant cause of disability worldwide. Novel approaches for the prevention and treatment of these disorders are needed. [...] Read more.
Inflammatory conditions, including allergic asthma and conditions in which chronic low-grade inflammation is a risk factor, such as stress-related psychiatric disorders, are prevalent and are a significant cause of disability worldwide. Novel approaches for the prevention and treatment of these disorders are needed. One approach is the use of immunoregulatory microorganisms, such as Mycobacterium vaccae NCTC 11659, which have anti-inflammatory, immunoregulatory, and stress-resilience properties. However, little is known about how M. vaccae NCTC 11659 affects specific immune cell targets, including monocytes, which can traffic to peripheral organs and the central nervous system and differentiate into monocyte-derived macrophages that, in turn, can drive inflammation and neuroinflammation. In this study, we investigated the effects of M. vaccae NCTC 11659 and subsequent lipopolysaccharide (LPS) challenge on gene expression in human monocyte-derived macrophages. THP-1 monocytes were differentiated into macrophages, exposed to M. vaccae NCTC 11659 (0, 10, 30, 100, 300 µg/mL), then, 24 h later, challenged with LPS (0, 0.5, 2.5, 250 ng/mL), and assessed for gene expression 24 h following challenge with LPS. Exposure to M. vaccae NCTC 11659 prior to challenge with higher concentrations of LPS (250 ng/mL) polarized human monocyte-derived macrophages with decreased IL12A, IL12B, and IL23A expression relative to IL10 and TGFB1 mRNA expression. These data identify human monocyte-derived macrophages as a direct target of M. vaccae NCTC 11659 and support the development of M. vaccae NCTC 11659 as a potential intervention to prevent stress-induced inflammation and neuroinflammation implicated in the etiology and pathophysiology of inflammatory conditions and stress-related psychiatric disorders. Full article
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26 pages, 3074 KiB  
Article
Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis
by Emmanuel O. Adewuyi, Eleanor K. O’Brien, Tenielle Porter and Simon M. Laws
Int. J. Mol. Sci. 2022, 23(24), 16199; https://doi.org/10.3390/ijms232416199 - 19 Dec 2022
Cited by 8 | Viewed by 7464
Abstract
Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and [...] Read more.
Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders. We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders—peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). Further analysis detects 35 significant (p < 4.37 × 10−5) bivariate local genetic correlations between cognitive traits, AD, and GIT disorders (including IBD). Mendelian randomisation analysis suggests a risk-decreasing causality of educational attainment, intelligence, and other cognitive traits on PUD and GERD, but not IBD, and a putative association of GERD with cognitive function decline. Gene-based analysis reveals a significant gene-level genetic overlap of cognitive traits with AD and GIT disorders (IBD inclusive, pbinomial-test = 1.18 × 10−3–2.20 × 10−16). Our study supports the protective roles of genetically-influenced educational attainments and other cognitive traits on the risk of GIT disorders and highlights a putative association of GERD with cognitive function decline. Findings from local genetic correlation analysis provide novel insights, indicating that the relationship of IBD with cognitive traits (and AD) will depend largely on their local effects across the genome. Full article
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Review

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27 pages, 1070 KiB  
Review
Impact of Microbiome–Brain Communication on Neuroinflammation and Neurodegeneration
by Iris Stolzer, Eveline Scherer, Patrick Süß, Veit Rothhammer, Beate Winner, Markus F. Neurath and Claudia Günther
Int. J. Mol. Sci. 2023, 24(19), 14925; https://doi.org/10.3390/ijms241914925 - 5 Oct 2023
Cited by 5 | Viewed by 2685
Abstract
The gut microbiome plays a pivotal role in maintaining human health, with numerous studies demonstrating that alterations in microbial compositions can significantly affect the development and progression of various immune-mediated diseases affecting both the digestive tract and the central nervous system (CNS). This [...] Read more.
The gut microbiome plays a pivotal role in maintaining human health, with numerous studies demonstrating that alterations in microbial compositions can significantly affect the development and progression of various immune-mediated diseases affecting both the digestive tract and the central nervous system (CNS). This complex interplay between the microbiota, the gut, and the CNS is referred to as the gut–brain axis. The role of the gut microbiota in the pathogenesis of neurodegenerative diseases has gained increasing attention in recent years, and evidence suggests that gut dysbiosis may contribute to disease development and progression. Clinical studies have shown alterations in the composition of the gut microbiota in multiple sclerosis patients, with a decrease in beneficial bacteria and an increase in pro-inflammatory bacteria. Furthermore, changes within the microbial community have been linked to the pathogenesis of Parkinson’s disease and Alzheimer’s disease. Microbiota–gut–brain communication can impact neurodegenerative diseases through various mechanisms, including the regulation of immune function, the production of microbial metabolites, as well as modulation of host-derived soluble factors. This review describes the current literature on the gut–brain axis and highlights novel communication systems that allow cross-talk between the gut microbiota and the host that might influence the pathogenesis of neuroinflammation and neurodegeneration. Full article
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38 pages, 2091 KiB  
Review
Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach—A Comprehensive Narrative Review
by Sara Uceda, Víctor Echeverry-Alzate, Manuel Reiriz-Rojas, Esther Martínez-Miguel, Ana Pérez-Curiel, Silvia Gómez-Senent and Ana Isabel Beltrán-Velasco
Int. J. Mol. Sci. 2023, 24(17), 13294; https://doi.org/10.3390/ijms241713294 - 27 Aug 2023
Cited by 3 | Viewed by 2194
Abstract
The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota–gut–brain axis as well as the implications of alterations in [...] Read more.
The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota–gut–brain axis as well as the implications of alterations in the microbial composition of patients with neurodegenerative diseases. The pathophysiology of neurodegenerative diseases with neuronal loss or death is analyzed, as well as the mechanisms of action of the main metabolites involved in the bidirectional communication through the microbiota–gut–brain axis. In addition, interventions targeting gut microbiota restructuring through fecal microbiota transplantation and the use of psychobiotics—pre- and pro-biotics—are evaluated as an opportunity to reduce the symptomatology associated with neurodegeneration in these pathologies. This review provides valuable information and facilitates a better understanding of the neurobiological mechanisms to be addressed in the treatment of neurodegenerative diseases. Full article
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