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The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases
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The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases

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 (20 March 2025) | Viewed by 15669

Special Issue Editors

Dr. Diego A. Moreno

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Guest Editor
Laboratorio de Fitoquímica y Alimentos Saludables (LabFAS), CEBAS, CSIC, Campus Universitario de Espinardo—25, E-30100 Espinardo, Murcia, Spain
Interests: phytochemicals; inflammation; obesity; health-centered agri-foods
Special Issues, Collections and Topics in MDPI journals
Dr. Bruno Ramos-Molina

E-Mail Website
Guest Editor
Obesity and Metabolism Research Group, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain
Interests: metabolism; obesity; diabetes; non-alcoholic fatty liver disease; nutrition; microbiota; metabolomics; epigenetics
Special Issues, Collections and Topics in MDPI journals
Dr. Antonio J. Ruiz-Alcaraz

E-Mail Website
Guest Editor
Department of Biochemistry, Molecular Biology B and Immunology, School of Medicine, University of Murcia, Regional Campus of International Excellence “Campus Mare Nostrum”, 30100 Murcia, Spain
Interests: inmune response; inflammation; immunonutrition; chronic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent decades, microbiome research has evolved rapidly, and, nowadays, it  not only represents a hot topic in basic, preclinical, and clinical research, but also for food science and nutrition, as well as for the pharmaceutical research, with implications for all the related industry of these areas.

The discovery of the gut–brain axis as the crucial connection between gut microbiota and the nervous system, and the growing body of evidence on the connections between gut microbiota and nervous system physiology and pathology is increasing awareness around bidirectional communication along the microbiota–gut–brain axis (MGBA) mediated by biologically active molecules and metabolites.

The appearance of intestinal dysbiosis leads to changes in the bidirectional relationship of the MGBA. It can also impact the brain, as well as the aging and the deterioration of the nervous system, driving towards pathological conditions such as Alzheimer’s disease and stroke.

Comparatively, the MGBA can be influenced by nutrients and bioactive molecules, inducing the secretion of specific hormones, which can then lead to changes in the energy metabolism and expenditure. The design of drugs, functional foods, and ingredients based on bioactive molecules exploiting the involved mechanisms may offer interesting alternatives for the treatment of non-communicable and high-prevalence diseases, such as obesity, type 2 diabetes, and other metabolic syndromes and co-morbidities.

This Special Issue aims to gain novel and applicable knowledge on all these aspects, with contributions from the different areas involved.

Dr. Diego A. Moreno
Dr. Bruno Ramos-Molina
Dr. Antonio J. Ruiz-Alcaraz
Guest Editors

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

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Keywords

  • gut–brain axis
  • gut microbiota
  • behavior
  • bioactive molecules
  • cognitive health
  • diabetes
  • in vitro models
  • in vivo models
  • hormones
  • intestine
  • obesity
  • probiotics
  • prebiotics
  • synbiotics

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Published Papers (6 papers)

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Research

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33 pages, 4269 KiB  
Article
Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach
by Irving Parra, Alan Carrasco-Carballo, Victoria Palafox-Sanchez, Isabel Martínez-García, José Aguilera, José L. Góngora-Alfaro, Irma Isela Aranda-González, Yousef Tizabi and Liliana Mendieta
Int. J. Mol. Sci. 2025, 26(10), 4507; https://doi.org/10.3390/ijms26104507 - 9 May 2025
Viewed by 330
Abstract
It is well established that the gut-brain axis (GBA) is a bidirectional communication between the gut and the brain. This axis, critical in maintaining overall homeostasis, is regulated at the neuronal, endocrine, and immunological levels, all of which may be influenced by the [...] Read more.
It is well established that the gut-brain axis (GBA) is a bidirectional communication between the gut and the brain. This axis, critical in maintaining overall homeostasis, is regulated at the neuronal, endocrine, and immunological levels, all of which may be influenced by the gut microbiota (GM). Therefore, dysbiosis or disruption in the GM may have serious consequences including neuroinflammation due to overactivation of the immune system. Strategies to reestablish GM integrity via use of probiotics are being pursued as novel therapeutic intervention in a variety of central and peripheral diseases. The mechanisms leading to dysbiosis or efficacy of probiotics, however, are not fully evident. Here, we performed computational analysis on two major probiotics, namely Lactobacillus Lacticaseibacillus rhamnosus GG (formerly named Lactobacillus rhamnosus, L. rhamnosus GG) and Bifidobacterium animalis spp. lactis (B. lactis or B. animalis) to not only shed some light on their mechanism(s) of action but also to identify potential molecular targets for novel probiotics. Using the PubMed web page and BioCyc Database Collection platform we specifically analyzed proteins affected by metabolites of these bacteria. Our results indicate that peroxisome proliferator-activated receptors (PPARs), nuclear receptor proteins that are involved in regulation of inflammation are key mediators of the neuroactive effect of probiotics. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases)
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22 pages, 6043 KiB  
Article
Correlations Between Amelioration of Rotenone-Induced Parkinson’s Symptoms by Amomum tsaoko Flavonoids and Gut Microbiota in Mice
by Li Liu, Yan Zhao, Weixing Yang, Lixiang Han, Xiaohan Mo, Jun Sheng, Yang Tian and Xiaoyu Gao
Int. J. Mol. Sci. 2025, 26(4), 1676; https://doi.org/10.3390/ijms26041676 - 16 Feb 2025
Viewed by 794
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease, but the existing therapeutic drugs for PD have limitations; thus, there is an urgent need to discover new methods of prevention and treatment. Amomum tsaoko Crevost et Lemarie (AT) is a classic traditional [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disease, but the existing therapeutic drugs for PD have limitations; thus, there is an urgent need to discover new methods of prevention and treatment. Amomum tsaoko Crevost et Lemarie (AT) is a classic traditional Chinese medicine and food. Its main pharmacological effect is the regulation of the gastrointestinal tract. To date, no studies on the use of AT or its extracts to treat PD have been reported. In this study, a rotenone-induced PD mouse model was utilized to evaluate the protective effect of Amomum tsaoko flavonoids (ATFs) and to elucidate the role of the gut microbiota in this effect. The results demonstrated that ATFs not only ameliorated the motor and constipation symptoms but also reduced the loss of nigrostriatal dopaminergic neurons. Furthermore, ATFs reduced the expression of inflammation-related genes (TNF-α, IL-1β, IL-6, COX-2, and MCP-1) and increased the expression of gut barrier-related genes (Muc-2, ZO-1, Occludin, Claudin3, and Claudin4) in the colon. Notably, ATFs were able to reverse rotenone-induced gut dysbiosis, including a significant decrease in the abundance of conditionally pathogenic bacteria (Desulfovibrio, Provotellaceae UCG-001, the Lachnospiraceae_NK4A136_group, norank_f_Erysipelotrichacea, and the Eubacterium nodatum group) and an increase in the abundance of probiotics (Bifidobacterium and Faecalibaculum). Interestingly, these genera were found to be significantly associated with PD motor symptoms and constipation indicators. This suggests that ATFs have the potential to alleviate PD symptoms through the modulation of gut microbes. These findings provide a solid foundation for further investigations into the anti-PD mechanism of ATFs and their potential in the prevention and treatment of PD. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases)
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18 pages, 4486 KiB  
Article
From the Microbiome to the Electrome: Implications for the Microbiota–Gut–Brain Axis
by Marwane Bourqqia-Ramzi, Jesús Mansilla-Guardiola, David Muñoz-Rodriguez, Elisa Quarta, Juan Lombardo-Hernandez, Antonio Murciano-Cespedosa, Francisco José Conejero-Meca, Álvaro Mateos González, Stefano Geuna, María Teresa Garcia-Esteban and Celia Herrera-Rincon
Int. J. Mol. Sci. 2024, 25(11), 6233; https://doi.org/10.3390/ijms25116233 - 5 Jun 2024
Cited by 2 | Viewed by 1916
Abstract
The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota–gut–brain brain axis and the bioelectrical communication [...] Read more.
The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota–gut–brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases)
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15 pages, 3553 KiB  
Article
Evidence of the Dysbiotic Effect of Psychotropics on Gut Microbiota and Capacity of Probiotics to Alleviate Related Dysbiosis in a Model of the Human Colon
by Yasmina Ait Chait, Walid Mottawea, Thomas A. Tompkins and Riadh Hammami
Int. J. Mol. Sci. 2023, 24(8), 7326; https://doi.org/10.3390/ijms24087326 - 15 Apr 2023
Cited by 7 | Viewed by 3689
Abstract
Growing evidence indicates that non-antibiotic therapeutics significantly impact human health by modulating gut microbiome composition and metabolism. In this study, we investigated the impact of two psychotropic drugs, aripiprazole and (S)-citalopram, on gut microbiome composition and its metabolic activity, as well as the [...] Read more.
Growing evidence indicates that non-antibiotic therapeutics significantly impact human health by modulating gut microbiome composition and metabolism. In this study, we investigated the impact of two psychotropic drugs, aripiprazole and (S)-citalopram, on gut microbiome composition and its metabolic activity, as well as the potential of probiotics to attenuate related dysbiosis using an ex vivo model of the human colon. After 48 h of fermentation, the two psychotropics demonstrated distinct modulatory effects on the gut microbiome. Aripiprazole, at the phylum level, significantly decreased the relative abundances of Firmicutes and Actinobacteria, while increasing the proportion of Proteobacteria. Moreover, the families Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also reduced by aripiprazole treatment compared to the control group. In addition, aripiprazole lowered the levels of butyrate, propionate, and acetate, as measured by gas chromatography (GC). On the other hand, (S)-citalopram increased the alpha diversity of microbial taxa, with no differences observed between groups at the family and genus level. Furthermore, a probiotic combination of Lacticaseibacillus rhamnosus HA-114 and Bifidobacterium longum R0175 alleviated gut microbiome alterations and increased the production of short-chain fatty acids to a similar level as the control. These findings provide compelling evidence that psychotropics modulate the composition and function of the gut microbiome, while the probiotic can mitigate related dysbiosis. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases)
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21 pages, 4673 KiB  
Article
YTHDF1 Attenuates TBI-Induced Brain-Gut Axis Dysfunction in Mice
by Peizan Huang, Min Liu, Jing Zhang, Xiang Zhong and Chunlong Zhong
Int. J. Mol. Sci. 2023, 24(4), 4240; https://doi.org/10.3390/ijms24044240 - 20 Feb 2023
Cited by 14 | Viewed by 3365
Abstract
The brain-gut axis (BGA) is a significant bidirectional communication pathway between the brain and gut. Traumatic brain injury (TBI) induced neurotoxicity and neuroinflammation can affect gut functions through BGA. N6-methyladenosine (m6A), as the most popular posttranscriptional modification of eukaryotic [...] Read more.
The brain-gut axis (BGA) is a significant bidirectional communication pathway between the brain and gut. Traumatic brain injury (TBI) induced neurotoxicity and neuroinflammation can affect gut functions through BGA. N6-methyladenosine (m6A), as the most popular posttranscriptional modification of eukaryotic mRNA, has recently been identified as playing important roles in both the brain and gut. However, whether m6A RNA methylation modification is involved in TBI-induced BGA dysfunction is not clear. Here, we showed that YTHDF1 knockout reduced histopathological lesions and decreased the levels of apoptosis, inflammation, and oedema proteins in brain and gut tissues in mice after TBI. We also found that YTHDF1 knockout improved fungal mycobiome abundance and probiotic (particularly Akkermansia) colonization in mice at 3 days post-CCI. Then, we identified the differentially expressed genes (DEGs) in the cortex between YTHDF1-knockout and WT mice. These genes were primarily enriched in the regulation of neurotransmitter-related neuronal signalling pathways, inflammatory signalling pathways, and apoptotic signalling pathways. This study reveals that the ITGA6-mediated cell adhesion molecule signalling pathway may be the key feature of m6A regulation in TBI-induced BGA dysfunction. Our results suggest that YTHDF1 knockout could attenuate TBI-induced BGA dysfunction. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases)
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Review

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15 pages, 1093 KiB  
Review
From Gut Microbiota to Brain Waves: The Potential of the Microbiome and EEG as Biomarkers for Cognitive Impairment
by Mahathi Krothapalli, Lauren Buddendorff, Hariom Yadav, Nathan D. Schilaty and Shalini Jain
Int. J. Mol. Sci. 2024, 25(12), 6678; https://doi.org/10.3390/ijms25126678 - 18 Jun 2024
Cited by 2 | Viewed by 3407
Abstract
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder and a leading cause of dementia. Aging is a significant risk factor for AD, emphasizing the importance of early detection since symptoms cannot be reversed once the advanced stage is reached. Currently, there is no [...] Read more.
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder and a leading cause of dementia. Aging is a significant risk factor for AD, emphasizing the importance of early detection since symptoms cannot be reversed once the advanced stage is reached. Currently, there is no established method for early AD diagnosis. However, emerging evidence suggests that the microbiome has an impact on cognitive function. The gut microbiome and the brain communicate bidirectionally through the gut–brain axis, with systemic inflammation identified as a key connection that may contribute to AD. Gut dysbiosis is more prevalent in individuals with AD compared to their cognitively healthy counterparts, leading to increased gut permeability and subsequent systemic inflammation, potentially causing neuroinflammation. Detecting brain activity traditionally involves invasive and expensive methods, but electroencephalography (EEG) poses as a non-invasive alternative. EEG measures brain activity and multiple studies indicate distinct patterns in individuals with AD. Furthermore, EEG patterns in individuals with mild cognitive impairment differ from those in the advanced stage of AD, suggesting its potential as a method for early indication of AD. This review aims to consolidate existing knowledge on the microbiome and EEG as potential biomarkers for early-stage AD, highlighting the current state of research and suggesting avenues for further investigation. Full article
(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases)
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