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Gut-Brain Axis: New Pathophysiological Scenarios and Therapeutic Strategies

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 (30 April 2022) | Viewed by 20422

Special Issue Editors

Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy
Interests: pain; inflammation; neuropathic pain; cannabinoid system; TRPM8; microbiota; gut-brain axis; neurodegenerative diseases-microbiota
Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy
Interests: behaviour; autism spectrum disorder; pain; inflammation; lipids; cannabinoid system; microbiota; gut-brain axis; neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Currently, the microbiota–gut–brain axis is emerging as a special scientific area of interest and a possible new target for different disorders. Modification in the gut microbiota composition appears to influence behaviour, cognitive processes, and the pain systems by modulating endocrine, immune, metabolic, and neuronal pathways. A better understanding of the mechanism by which the gut–brain axis is involved in chronic diseases may open new therapeutic strategies.

The aim of this Special Issue is focused on understanding how an alteration of gut functionality, such as dysbiosis, is involved in different diseases (i.e., neurological and neurodegenerative diseases, chronic pain, obesity, and inflammatory bowel diseases), looking at the identification of specific pathways, risk factors, or conditions to develop better and safer therapies. We invite all interested researchers to submit review articles or original papers related to the topic of this Special Issue, guided by the keywords below.

Dr. Roberto R. Russo
Dr. Claudia Cristiano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • chronic pain
  • microbiota composition
  • gut–brain axis
  • chronic diseases
  • neurological disease
  • animal models
  • neurodegenerative disease
  • therapeutics
  • molecular pathway

Published Papers (6 papers)

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Research

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19 pages, 7054 KiB  
Article
Dual-Hit Model of Parkinson’s Disease: Impact of Dysbiosis on 6-Hydroxydopamine-Insulted Mice—Neuroprotective and Anti-Inflammatory Effects of Butyrate
Int. J. Mol. Sci. 2022, 23(12), 6367; https://doi.org/10.3390/ijms23126367 - 07 Jun 2022
Cited by 13 | Viewed by 2897
Abstract
Recent evidence highlights Parkinson’s disease (PD) initiation in the gut as the prodromal phase of neurodegeneration. Gut impairment due to microbial dysbiosis could affect PD pathogenesis and progression. Here, we propose a two-hit model of PD through ceftriaxone (CFX)-induced dysbiosis and gut inflammation [...] Read more.
Recent evidence highlights Parkinson’s disease (PD) initiation in the gut as the prodromal phase of neurodegeneration. Gut impairment due to microbial dysbiosis could affect PD pathogenesis and progression. Here, we propose a two-hit model of PD through ceftriaxone (CFX)-induced dysbiosis and gut inflammation before the 6-hydroxydopamine (6-OHDA) intrastriatal injection to mimic dysfunctional gut-associated mechanisms preceding PD onset. Therefore, we showed that dysbiosis and gut damage amplified PD progression, worsening motor deficits induced by 6-OHDA up to 14 days post intrastriatal injection. This effect was accompanied by a significant increase in neuronal dopaminergic loss (reduced tyrosine hydroxylase expression and increased Bcl-2/Bax ratio). Notably, CFX pretreatment also enhanced systemic and colon inflammation of dual-hit subjected mice. The exacerbated inflammatory response ran in tandem with a worsening of colonic architecture and gut microbiota perturbation. Finally, we demonstrated the beneficial effect of post-biotic sodium butyrate in limiting at once motor deficits, neuroinflammation, and colon damage and re-shaping microbiota composition in this novel dual-hit model of PD. Taken together, the bidirectional communication of the microbiota–gut–brain axis and the recapitulation of PD prodromal/pathogenic features make this new paradigm a useful tool for testing or repurposing new multi-target compounds in the treatment of PD. Full article
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16 pages, 3675 KiB  
Article
Supplementation with SCFAs Re-Establishes Microbiota Composition and Attenuates Hyperalgesia and Pain in a Mouse Model of NTG-Induced Migraine
Int. J. Mol. Sci. 2022, 23(9), 4847; https://doi.org/10.3390/ijms23094847 - 27 Apr 2022
Cited by 7 | Viewed by 1681
Abstract
Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we [...] Read more.
Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we evaluated the role of the short-chain fatty acids (SCFAs) as sodium propionate (SP) and sodium butyrate (SB) on microbiota profile and intestinal permeability in a mouse model of migraine induced by nitroglycerine (NTG). The mice were orally administered SB and SP at the dose of 10, 30 and 100 mg/kg, 5 min after NTG intraperitoneal injections. Behavioral tests were used to evaluate migraine-like pain. Histological and molecular analyses were performed on the intestine. The composition of the intestinal microbiota was extracted from frozen fecal samples and sequenced with an Illumina MiSeq System. Our results demonstrated that the SP and SB treatments attenuated hyperalgesia and pain following NTG injection. Moreover, SP and SB reduced histological damage in the intestine and restored intestinal permeability and the intestinal microbiota profile. These results provide corroborating evidence that SB and SP exert a protective effect on central sensitization induced by NTG through a modulation of intestinal microbiota, suggesting the potential application of SCFAs as novel supportive therapies for intestinal disfunction associated with migraine. Full article
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24 pages, 3000 KiB  
Article
Supplementation with Lactiplantibacillus plantarum IMC 510 Modifies Microbiota Composition and Prevents Body Weight Gain Induced by Cafeteria Diet in Rats
Int. J. Mol. Sci. 2021, 22(20), 11171; https://doi.org/10.3390/ijms222011171 - 16 Oct 2021
Cited by 11 | Viewed by 2514
Abstract
Changes in functionality and composition of gut microbiota (GM) have been associated and may contribute to the development and maintenance of obesity and related diseases. The aim of our study was to investigate for the first time the impact of Lactiplantibacillus (L.) plantarum [...] Read more.
Changes in functionality and composition of gut microbiota (GM) have been associated and may contribute to the development and maintenance of obesity and related diseases. The aim of our study was to investigate for the first time the impact of Lactiplantibacillus (L.) plantarum IMC 510 in a rat model of diet-induced obesity, specifically in the cafeteria (CAF) diet. This diet provides a strong motivation to voluntary overeat, due to the palatability and variety of selected energy-dense foods. The oral administration for 84 days of this probiotic strain, added to the CAF diet, decreased food intake and body weight gain. Accordingly, it ameliorated body mass index, liver and white adipose tissue weight, hepatic lipid accumulation, adipocyte size, serum parameters, including glycemia and low-density lipoprotein levels, in CAF fed rats, potentially through leptin control. In this scenario, L. plantarum IMC 510 showed also beneficial effects on GM, limiting the microbial imbalance established by long exposure to CAF diet and preserving the proportion of different bacterial taxa. Further research is necessary to better elucidate the relationship between GM and overweight and then the mechanism of action by which L. plantarum IMC 510 modifies weight. However, these promising results prompt a clear advantage of probiotic supplementation and identify a new potential probiotic as a novel and safe therapeutic approach in obesity prevention and management. Full article
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Review

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25 pages, 1123 KiB  
Review
The Role of Psychobiotics in Supporting the Treatment of Disturbances in the Functioning of the Nervous System—A Systematic Review
Int. J. Mol. Sci. 2022, 23(14), 7820; https://doi.org/10.3390/ijms23147820 - 15 Jul 2022
Cited by 3 | Viewed by 3993
Abstract
Stress and anxiety are common phenomena that contribute to many nervous system dysfunctions. More and more research has been focusing on the importance of the gut–brain axis in the course and treatment of many diseases, including nervous system disorders. This review aims to [...] Read more.
Stress and anxiety are common phenomena that contribute to many nervous system dysfunctions. More and more research has been focusing on the importance of the gut–brain axis in the course and treatment of many diseases, including nervous system disorders. This review aims to present current knowledge on the influence of psychobiotics on the gut–brain axis based on selected diseases, i.e., Alzheimer’s disease, Parkinson’s disease, depression, and autism spectrum disorders. Analyses of the available research results have shown that selected probiotic bacteria affect the gut–brain axis in healthy people and people with selected diseases. Furthermore, supplementation with probiotic bacteria can decrease depressive symptoms. There is no doubt that proper supplementation improves the well-being of patients. Therefore, it can be concluded that the intestinal microbiota play a relevant role in disorders of the nervous system. The microbiota–gut–brain axis may represent a new target in the prevention and treatment of neuropsychiatric disorders. However, this topic needs more research. Such research could help find effective treatments via the modulation of the intestinal microbiome. Full article
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23 pages, 3164 KiB  
Review
PARK7/DJ-1 as a Therapeutic Target in Gut-Brain Axis Diseases
Int. J. Mol. Sci. 2022, 23(12), 6626; https://doi.org/10.3390/ijms23126626 - 14 Jun 2022
Cited by 6 | Viewed by 3668
Abstract
It is increasingly known that Parkinson’s (PD) and Alzheimer’s (AD) diseases occur more frequently in patients with inflammatory gastrointestinal diseases including inflammatory bowel (IBD) or celiac disease, indicating a pathological link between them. Although epidemiological observations suggest the existence of the gut-brain axis [...] Read more.
It is increasingly known that Parkinson’s (PD) and Alzheimer’s (AD) diseases occur more frequently in patients with inflammatory gastrointestinal diseases including inflammatory bowel (IBD) or celiac disease, indicating a pathological link between them. Although epidemiological observations suggest the existence of the gut-brain axis (GBA) involving systemic inflammatory and neural pathways, little is known about the exact molecular mechanisms. Parkinson’s disease 7 (PARK7/DJ-1) is a multifunctional protein whose protective role has been widely demonstrated in neurodegenerative diseases, including PD, AD, or ischemic stroke. Recent studies also revealed the importance of PARK7/DJ-1 in the maintenance of the gut microbiome and also in the regulation of intestinal inflammation. All these findings suggest that PARK7/DJ-1 may be a link and also a potential therapeutic target in gut and brain diseases. In this review, therefore, we discuss our current knowledge about PARK7/DJ-1 in the context of GBA diseases. Full article
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19 pages, 2684 KiB  
Review
Organ-on-a-Chip for Studying Gut-Brain Interaction Mediated by Extracellular Vesicles in the Gut Microenvironment
Int. J. Mol. Sci. 2021, 22(24), 13513; https://doi.org/10.3390/ijms222413513 - 16 Dec 2021
Cited by 16 | Viewed by 4362
Abstract
Extracellular vesicles (EVs) are a group of membrane vesicles that play important roles in cell-to-cell and interspecies/interkingdom communications by modulating the pathophysiological conditions of recipient cells. Recent evidence has implied their potential roles in the gut–brain axis (GBA), which is a complex bidirectional [...] Read more.
Extracellular vesicles (EVs) are a group of membrane vesicles that play important roles in cell-to-cell and interspecies/interkingdom communications by modulating the pathophysiological conditions of recipient cells. Recent evidence has implied their potential roles in the gut–brain axis (GBA), which is a complex bidirectional communication system between the gut environment and brain pathophysiology. Despite the evidence, the roles of EVs in the gut microenvironment in the GBA are less highlighted. Moreover, there are critical challenges in the current GBA models and analyzing techniques for EVs, which may hinder the research. Currently, advances in organ-on-a-chip (OOC) technologies have provided a promising solution. Here, we review the potential effects of EVs occurring in the gut environment on brain physiology and behavior and discuss how to apply OOCs to research the GBA mediated by EVs in the gut microenvironment. Full article
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