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Molecular Mechanisms in the Microbiome–Brain–Gut Axis 2.0

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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 (27 February 2024) | Viewed by 8003

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Special Issue Editor

Dr. Gerard M. Moloney

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Guest Editor

Department of Anatomy and Neuroscience, University College, Cork, Ireland
Interests: microRNA; microbiota; brain; gut; non-coding
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut microbiome enables a constant transfer of information between the gut and the brain and there are many unexplored molecular pathways underpinning this transfer. The aim of this special edition will be to harness the key current research in the field into a compelling collection of novel research in the field.

This scope of this special edition will be novel research that examines how key unexplored molecular pathways influence the gut microbiome, the brain, and the gut, preferably showing an interaction between the different nodes of this relationship. The preferred theme of the research will be from a molecular biology point of view with mechanistic experiments consisting of either an in-vitro, in-silico or in-vivo nature forming the overall structure of submissions. Furthermore, this special edition will outline how the key nodes of the Microbiome-Brain-Gut Axis when disturbed, influence disease in the gut or the brain. Finally, it is hoped that of the articles submitted, some will show how therapeutic interventions targeting one aspect of the Microbiome-Brain-Gut Axis can repair other points along the axis. For example, can modulating the composition of the microbiome, influence the function of the brain via chemical or probiotic intervention (amongst many more).

Dr. Gerard M. Moloney
Guest Editor

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.

Related Special Issue

Molecular Mechanisms in the Microbiome–Brain–Gut Axis in International Journal of Molecular Sciences (10 articles)

Published Papers (4 papers)

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Research

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13 pages, 2948 KiB

Open AccessArticle

Indole-3-Propionic Acid, a Gut Microbiota-Derived Tryptophan Metabolite, Promotes Endothelial Dysfunction Impairing Purinergic-Induced Nitric Oxide Release in Endothelial Cells

by Federica Geddo, Susanna Antoniotti, Maria Pia Gallo and Giulia Querio

Int. J. Mol. Sci. 2024, 25(6), 3389; https://doi.org/10.3390/ijms25063389 - 16 Mar 2024

Viewed by 919

Abstract

Different gut microbiota-derived metabolites influence cardiovascular function, and, among all, the role of indole-3-propionic acid (IPA), from tryptophan metabolism, shows controversial effects. The aim of this study was to evaluate its role in endothelial dysfunction. IPA effects were studied on bovine aortic endothelial cells (BAE-1). First, IPA cytotoxicity was evaluated by an MTS assay. Then, the levels of intracellular reactive oxygen species (ROS) were evaluated by a microplate reader or fluorescence microscopy with the CellROX^® Green probe, and nitric oxide (NO) production was studied by fluorescence microscopy with the DAR4M-AM probe after acute or chronic treatment. Finally, immunoblotting analysis for endothelial nitric oxide synthase (eNOS) phosphorylation (p-eNOS) was performed. In BAE-1, IPA was not cytotoxic, except for the highest concentration (5 mM) after 48 h of treatment, and it showed neither oxidant nor antioxidant activity. However, the physiological concentration of IPA (1 μM) significantly reduced NO released by adenosine triphosphate (ATP)-stimulated BAE-1. These last data were confirmed by Western blot analysis, where IPA induced a significant reduction in p-eNOS in purinergic-stimulated BAE-1. Given these data, we can speculate that IPA negatively affects the physiological control of vascular tone by impairing the endothelial NO release induced by purinergic stimulation. These results represent a starting point for understanding the mechanisms underlying the relationship between gut microbiota metabolites and cardiometabolic health. Full article

(This article belongs to the Special Issue Molecular Mechanisms in the Microbiome–Brain–Gut Axis 2.0)

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21 pages, 2104 KiB

Open AccessArticle

A Diet Enriched with Lacticaseibacillus rhamnosus HN001 and Milk Fat Globule Membrane Alters the Gut Microbiota and Decreases Amygdala GABA a Receptor Expression in Stress-Sensitive Rats

by Julie E. Dalziel, Gosia Zobel, Hilary Dewhurst, Charlotte Hurst, Trent Olson, Raquel Rodriguez-Sanchez, Louise Mace, Nabil Parkar, Caroline Thum, Rina Hannaford, Karl Fraser, Alastair MacGibbon, Shalome A. Bassett, James Dekker, Rachel C. Anderson and Wayne Young

Int. J. Mol. Sci. 2023, 24(13), 10433; https://doi.org/10.3390/ijms241310433 - 21 Jun 2023

Cited by 3 | Viewed by 1948

Abstract

Brain signalling pathways involved in subclinical anxiety and depressed mood can be modulated via the gut brain axis (GBA), providing the potential for diet and dietary components to affect mood. We investigated behavioural, physiological and gut microbiome responses to the Lacticaseibacillus rhamnosus strain HN001 (LactoB HN001™), which has been shown to reduce postpartum anxiety and depression, and a milk fat globule membrane-enriched product, Lipid 70 (Surestart^TM MFGM Lipid 70), which has been implicated in memory in stress-susceptible Wistar Kyoto rats. We examined behaviour in the open field, elevated plus maze and novel object recognition tests in conjunction with the expression of host genes in neuro-signalling pathways, and we also assessed brain lipidomics. Treatment-induced alterations in the caecal microbiome and short-chain fatty acid (SCFA) profiles were also assessed. Neither ingredient induced behavioural changes or altered the brain lipidome (separately or when combined). However, with regard to brain gene expression, the L. rhamnosus HN001 + Lipid 70 combination produced a synergistic effect, reducing GABAA subunit expression in the amygdala (Gabre, Gat3, Gabrg1) and hippocampus (Gabrd). Treatment with L. rhamnosus HN001 alone altered expression of the metabotropic glutamate receptor (Grm4) in the amygdala but produced only minor changes in gut microbiota composition. In contrast, Lipid 70 alone did not alter brain gene expression but produced a significant shift in the gut microbiota profile. Under the conditions used, there was no observed effect on rat behaviour for the ingredient combination. However, the enhancement of brain gene expression by L. rhamnosus HN001 + Lipid 70 implicates synergistic actions on region-specific neural pathways associated with fear, anxiety, depression and memory. A significant shift in the gut microbiota profile also occurred that was mainly attributable to Lipid 70. Full article

(This article belongs to the Special Issue Molecular Mechanisms in the Microbiome–Brain–Gut Axis 2.0)

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31 pages, 40185 KiB

Open AccessArticle

Combined Omics Analysis Further Unveils the Specific Role of Butyrate in Promoting Growth in Early-Weaning Animals

by Bin Zhang, Mengqi Liu, Zhengkai Yue, Xiaoyang Chen, Chenyang Li, Lei Liu and Fuchang Li

Int. J. Mol. Sci. 2023, 24(2), 1787; https://doi.org/10.3390/ijms24021787 - 16 Jan 2023

Cited by 3 | Viewed by 2130

Abstract

Abnormal mutations in the microbial structure of early-weaning mammals are an important cause of enteritis. Based on the multiple known beneficial functions of butyrate, we hypothesized that butyrate would alleviate the imbalance of intestinal homeostasis induced by early weaning in animals. However, the mechanisms of action between butyrate and intestinal microbes are still poorly explored. In this study, we aimed to investigate whether butyrate exerts beneficial effects on the structure of the intestinal flora of weanling rabbits and their intestinal homeostasis, growth and development, and we attempted to elucidate the potential mechanisms of action through a combined omics analysis. We found that dietary butyrate upregulated the transcription of tight junction-related proteins in the epithelial barrier and improved the intestinal microbial structure by suppressing harmful bacteria and promoting beneficial ones. Intestinal and plasma metabolomes were also altered. The bile acid secretion, α-linolenic acid, apoptotic, and prostate cancer pathways responded to the positive dietary butyrate-induced metabolic changes in the weanling rabbits, resulting in the inhibition of inflammation, improved antioxidant capacity, increased rates of cell proliferation and survival, and decreased levels of apoptosis. Additionally, dietary butyrate suppressed the release of pro-inflammatory factors and enhanced positive appetite regulation, which increased the average daily gain of the rabbits. These results demonstrated that dietary butyrate can help maintain the integrity of the intestinal epithelial barrier, improve the structural composition of the intestinal microflora, enhance organismal metabolism, inhibit inflammation, reduce post-weaning anorexia, and promote growth and development in early-weaning rabbits. These positive effects of dietary butyrate were exerted via the modulation of the microbe–gut–brain axis. Full article

(This article belongs to the Special Issue Molecular Mechanisms in the Microbiome–Brain–Gut Axis 2.0)

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Review

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27 pages, 1086 KiB

Open AccessReview

Gut Microbiome Dysbiosis as a Potential Risk Factor for Idiopathic Toe-Walking in Children: A Review

by Svetlana Kononova, Mikhail Kashparov, Wenyu Xue, Natalia Bobkova, Sergey Leonov and Nikolaj Zagorodny

Int. J. Mol. Sci. 2023, 24(17), 13204; https://doi.org/10.3390/ijms241713204 - 25 Aug 2023

Viewed by 2345

Abstract

Idiopathic toe walking (ITW) occurs in about 5% of children. Orthopedic treatment of ITW is complicated by the lack of a known etiology. Only half of the conservative and surgical methods of treatment give a stable positive result of normalizing gait. Available data indicate that the disease is heterogeneous and multifactorial. Recently, some children with ITW have been found to have genetic variants of mutations that can lead to the development of toe walking. At the same time, some children show sensorimotor impairment, but these studies are very limited. Sensorimotor dysfunction could potentially arise from an imbalanced production of neurotransmitters that play a crucial role in motor control. Using the data obtained in the studies of several pathologies manifested by the association of sensory–motor dysfunction and intestinal dysbiosis, we attempt to substantiate the notion that malfunction of neurotransmitter production is caused by the imbalance of gut microbiota metabolites as a result of dysbiosis. This review delves into the exciting possibility of a connection between variations in the microbiome and ITW. The purpose of this review is to establish a strong theoretical foundation and highlight the benefits of further exploring the possible connection between alterations in the microbiome and TW for further studies of ITW etiology. Full article

(This article belongs to the Special Issue Molecular Mechanisms in the Microbiome–Brain–Gut Axis 2.0)

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