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Life
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The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases
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The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (2 November 2021) | Viewed by 33357

Special Issue Editors

Dr. Fabiana Piscitelli

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Guest Editor
Endocannabinoid Research Group (ERG) Institute of Biomolecular Chemistry (ICB) Consiglio Nazionale delle Ricerche (CNR), 00015 Rome, Italy
Interests: endocannabinoids; lipidomics; Alzheimer; neuroscience; gut-brain axis; TBI
Dr. Tiziana Bisogno

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Guest Editor
Endocannabinoid Research Group (ERG), Institute of Translational Pharmacology (IFT), Consiglio Nazionale delle Ricerche (CNR), 00185 Rome, Italy
Interests: bioactive lipids; neurodegeneration

Special Issue Information

Dear Colleagues,

The concept of the gut–brain axis (GBA), the bidirectional channel between the enteric and the central nervous systems, is far from new, but recent advances have described the importance of the gut microbiota in influencing these interactions. This bidirectional communication between the “big brain” and the “little brain” involves complex crosstalk between the endocrine (hypothalamic–pituitary–adrenal axis), immune (cytokines and chemokines), and the autonomic nervous system (ANS). Regulation of the microbiota–brain–gut axis is essential for maintaining homeostasis, including that of the CNS, and perturbation of these systems may affect transition between health and disease. Disruption of the gut–brain axis has been shown to be involved in the pathogenesis of a diverse range of diseases, including neurodegenerative diseases. The etiologies of most neurodegenerative diseases are multifactorial, wherein a close interaction of genetic and environmental factors seem to initiate the pathological process. However, accumulating evidence has suggested that alteration of the brain–gut microbiota homeostasis could worsen the etiology, pathogenesis, and/or progression of disorders such as multiple sclerosis (MS), Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and others. Understanding microbiota–gut–brain communications is an exciting but challenging area of research that may contribute new insights into these pathways, which in turn might lead to novel treatment strategies in neurodegenerative diseases.

This Special Issue, “The Microbiota–Gut–Brain Axis in Neurodegenerative Diseases”, is gathering contributions that seek to advance the understanding of the role of the gut–brain axis in neurodegenerative diseases. This Special Issue calls for reviews as well as original research articles documenting our progress in and current understanding of this exciting and insightful field of research from a multidisciplinary perspective.


Dr. Fabiana Piscitelli
Dr. Tiziana Bisogno
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gut–brain axis
  • gut microbiota
  • gut microbiota and drug metabolism
  • “omics” analysis of gut microbiome in neurodegenerative diseases
  • Alzheimer’s disease
  • Parkinson’s disease
  • multiple sclerosis
  • amyotrophic lateral sclerosis

Published Papers (7 papers)

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Research

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31 pages, 7007 KiB  
Article
Amelioration of Alzheimer’s Disease by Gut-Pancreas-Liver-Brain Interaction in an App Knock-In Mouse Model
by Mayumi Minamisawa, Yuma Sato, Eitarou Ishiguro, Tetsuyuki Taniai, Taiichi Sakamoto, Gota Kawai, Takashi Saito and Takaomi C. Saido
Life 2022, 12(1), 34; https://doi.org/10.3390/life12010034 - 27 Dec 2021
Cited by 3 | Viewed by 4313
Abstract
In this study, we observed disease progression, changes in the gut microbiota, and interactions among the brain, liver, pancreas, and intestine in a mouse model of Alzheimer’s disease (AD), in addition to attempting to inhibit disease progression through the dietary supplementation of L-arginine [...] Read more.
In this study, we observed disease progression, changes in the gut microbiota, and interactions among the brain, liver, pancreas, and intestine in a mouse model of Alzheimer’s disease (AD), in addition to attempting to inhibit disease progression through the dietary supplementation of L-arginine and limonoids. Wild-type mice (WC) and AD mice were fed a normal diet (AC), a diet supplemented with L-arginine and limonoids (ALA), or a diet containing only limonoids (AL) for 12–64 weeks. The normal diet-fed WC and AC mice showed a decrease in the diversity of the gut microbiota, with an increase in the Firmicutes/Bacteroidetes ratio, and bacterial translocation. Considerable bacterial translocation to the pancreas and intense inflammation of the pancreas, liver, brain, and intestinal tissues were observed in the AC mice from alterations in the gut microbiota. The ALA diet or AL diet-fed mice showed increased diversity of the bacterial flora and suppressed oxidative stress and inflammatory responses in hepatocytes and pancreatic cells, bacterial translocation, and neurodegeneration of the brain. These findings suggest that L-arginine and limonoids help in maintaining the homeostasis of the gut microbiota, pancreas, liver, brain, and gut in AD mice. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)
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18 pages, 4377 KiB  
Article
Comparison of the Intestinal Microbiome of Italian Patients with Multiple Sclerosis and Their Household Relatives
by Paola Galluzzo, Fanny Claire Capri, Luca Vecchioni, Sabrina Realmuto, Luca Scalisi, Salvatore Cottone, Domenico Nuzzo and Rosa Alduina
Life 2021, 11(7), 620; https://doi.org/10.3390/life11070620 - 26 Jun 2021
Cited by 17 | Viewed by 3282
Abstract
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, caused by a combination of genetic and environmental factors. In recent years, a role in MS pathogenesis was assigned to the gut microbiota. However, different signatures of gut dysbiosis have [...] Read more.
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, caused by a combination of genetic and environmental factors. In recent years, a role in MS pathogenesis was assigned to the gut microbiota. However, different signatures of gut dysbiosis have been shown to depend on environmental factors, like diet and lifestyle. In this study, we compared the gut microbiome in MS patients and their household healthy relatives sharing lifestyle and environmental factors. Faecal metagenomic DNA was extracted and the V3–V4 regions of the conserved bacterial 16S ribosomal RNA gene were amplified and sequenced. While overall bacterial communities were similar, specific families differed between healthy and MS subjects. We observed an increase in Ruminococcaceae, Christensenellaceae, Desulfovibrionaceae, Clostridiales, and Family XIII in MS patients, while Bacteroidaceae, Tannerellaceae, Veillonellaceae, and Burkholderiaceae were more abundant in healthy controls. In addition, principle coordinate analysis showed that the gut microbiome of all MS patients formed a cluster being less diverse than the household relatives and that gut microbiota of MS patients with EDSS 4.5–7 formed a distinct cluster in respect to their controls. Overall, our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and evidenced the importance of environmental factors in shaping the gut microbiome. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)
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Review

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19 pages, 760 KiB  
Review
The Endocannabinoid System: A Bridge between Alzheimer’s Disease and Gut Microbiota
by Tiziana Bisogno, Anna Lauritano and Fabiana Piscitelli
Life 2021, 11(9), 934; https://doi.org/10.3390/life11090934 - 8 Sep 2021
Cited by 9 | Viewed by 4363
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease that progresses from mild cognitive impairment to severe dementia over time. The main clinical hallmarks of the disease (e.g., beta-amyloid plaques and neurofibrillary tangles) begin during preclinical AD when cognitive deficits are not yet apparent. Hence, [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative disease that progresses from mild cognitive impairment to severe dementia over time. The main clinical hallmarks of the disease (e.g., beta-amyloid plaques and neurofibrillary tangles) begin during preclinical AD when cognitive deficits are not yet apparent. Hence, a more profound understanding of AD pathogenesis is needed to develop new therapeutic strategies. In this context, the endocannabinoid (eCB) system and the gut microbiome are increasingly emerging as important players in maintaining the general homeostasis and the health status of the host. However, their interaction has come to light just recently with gut microbiota regulating the eCB tone at both receptor and enzyme levels in intestinal and adipose tissues. Importantly, eCB system and gut microbiome, have been suggested to play a role in AD in both animal and human studies. Therefore, the microbiome gut-brain axis and the eCB system are potential common denominators in the AD physiopathology. Hence, the aim of this review is to provide a general overview on the role of both the eCB system and the microbiome gut-brain axis in AD and to suggest possible mechanisms that underlie the potential interplay of these two systems. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)
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12 pages, 526 KiB  
Review
The Role of Gut Microbiota in Aging and Aging Related Neurodegenerative Disorders: Insights from Drosophila Model
by Yan Kong, Liyuan Wang and Baichun Jiang
Life 2021, 11(8), 855; https://doi.org/10.3390/life11080855 - 20 Aug 2021
Cited by 11 | Viewed by 3825
Abstract
Aging is characterized by a time dependent impairment of physiological function and increased susceptibility to death. It is the major risk factor for neurodegeneration. Neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the main causes of dementia in the old [...] Read more.
Aging is characterized by a time dependent impairment of physiological function and increased susceptibility to death. It is the major risk factor for neurodegeneration. Neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the main causes of dementia in the old population. Gut microbiota is a community of microorganisms colonized in the gastrointestinal (GI) tract. The alteration of gut microbiota has been proved to be associated with aging and aging related neurodegeneration. Drosophila is a powerful tool to study microbiota-mediated physiological and pathological functions. Here, we summarize the recent advances using Drosophila as model organisms to clarify the molecular mechanisms and develop a therapeutic method targeting microbiota in aging and aging-related neurodegenerative disorders. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)
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20 pages, 1896 KiB  
Review
The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease
by Gianfranco Natale, Larisa Ryskalin, Gabriele Morucci, Gloria Lazzeri, Alessandro Frati and Francesco Fornai
Life 2021, 11(8), 732; https://doi.org/10.3390/life11080732 - 22 Jul 2021
Cited by 15 | Viewed by 7781
Abstract
The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial [...] Read more.
The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to identifying various neuronal cytotypes belonging to ENS in baseline conditions. The second part of the study provides evidence on how these very same neurons are altered during Parkinson’s disease. In fact, although being defined as a movement disorder, Parkinson’s disease features a number of degenerative alterations, which often anticipate motor symptoms. Among these, the GI tract is often involved, and for this reason, it is important to assess its normal and pathological structure. A deeper knowledge of the ENS is expected to improve the understanding of diagnosis and treatment of Parkinson’s disease. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)
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11 pages, 535 KiB  
Review
Microbiota Gut–Brain Axis in Ischemic Stroke: A Narrative Review with a Focus about the Relationship with Inflammatory Bowel Disease
by Emanuele Sinagra, Gaia Pellegatta, Valentina Guarnotta, Marcello Maida, Francesca Rossi, Giuseppe Conoscenti, Socrate Pallio, Rita Alloro, Dario Raimondo, Fabio Pace and Andrea Anderloni
Life 2021, 11(7), 715; https://doi.org/10.3390/life11070715 - 19 Jul 2021
Cited by 14 | Viewed by 3639
Abstract
The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer’s disease, and Parkinson’s disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only [...] Read more.
The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer’s disease, and Parkinson’s disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only the focus of neuroscience, but also the starting point for research regarding many diseases such as inflammatory bowel diseases (IBD). The bi-directional interaction between gut microbiota and the brain is not completely understood. The aim of this review is to sum up the evidencesconcerningthe role of the gut–brain microbiota axis in ischemic stroke and to highlight the more recent evidences about the potential role of the gut–brain microbiota axis in the interaction between inflammatory bowel disease and ischemic stroke. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)
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20 pages, 4672 KiB  
Review
Association of Gut Microbiome Dysbiosis with Neurodegeneration: Can Gut Microbe-Modifying Diet Prevent or Alleviate the Symptoms of Neurodegenerative Diseases?
by Li Yang Tan, Xin Yi Yeo, Han-Gyu Bae, Delia Pei Shan Lee, Roger C. Ho, Jung Eun Kim, Dong-Gyu Jo and Sangyong Jung
Life 2021, 11(7), 698; https://doi.org/10.3390/life11070698 - 15 Jul 2021
Cited by 10 | Viewed by 4601
Abstract
The central nervous system was classically perceived as anatomically and functionally independent from the other visceral organs. But in recent decades, compelling evidence has led the scientific community to place a greater emphasis on the role of gut microbes on the brain. Pathological [...] Read more.
The central nervous system was classically perceived as anatomically and functionally independent from the other visceral organs. But in recent decades, compelling evidence has led the scientific community to place a greater emphasis on the role of gut microbes on the brain. Pathological observations and early gastrointestinal symptoms highlighted that gut dysbiosis likely precedes the onset of cognitive deficits in Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients. The delicate balance in the number and functions of pathogenic microbes and alternative probiotic populations is critical in the modulation of systemic inflammation and neuronal health. However, there is limited success in restoring healthy microbial biodiversity in AD and PD patients with general probiotics interventions and fecal microbial therapies. Fortunately, the gut microflora is susceptible to long-term extrinsic influences such as lifestyle and dietary choices, providing opportunities for treatment through comparatively individual-specific control of human behavior. In this review, we examine the impact of restrictive diets on the gut microbiome populations associated with AD and PD. The overall evidence presented supports that gut dysbiosis is a plausible prelude to disease onset, and early dietary interventions are likely beneficial for the prevention and treatment of progressive neurodegenerative diseases. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)
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