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The (Microbiota)–Gut–Brain Axis: Hype or Revolution?
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The (Microbiota)–Gut–Brain Axis: Hype or Revolution?

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (22 June 2018) | Viewed by 108305

Special Issue Editor

Dr. Lukas Van Oudenhove

E-Mail Website
Guest Editor
Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
Interests: gut–brain axis; functional gastrointestinal disorders; neuroscience; psychophysiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, the scope of research on the bidirectional communication system between the gastrointestinal tract and the central nervous system—known as the “gut–brain axis”—has broadened dramatically. Initially, gut–brain axis research was almost exclusively focused on gastrointestinal symptom generation and perception. However, recent methodological advances in molecular biology and chemistry as well as bioinformatics allowing, among others, the study of the composition and function of the gut microbiota in vivo have expanded the scope of gut–brain axis research far beyond its initial narrow boundaries as a niche within “neurogastroenterology”. More specifically, recent studies have demonstrated a profound impact of nutritional as well as gut microbiota manipulations on psychobiological processes in rodents. Efforts towards translation to humans are beginning to be made, but are still limited, and results are somewhat mixed.

In this Special Issue on “The (Microbiota)–Gut–Brain Axis: Hype or Revolution?” we invite researchers to submit original research and review articles on the microbiota–gut–brain axis, including but not limited to the following topics:

  • gut–brain signaling mechanisms underlying gastrointestinal symptom generation and perception in health and functional gastrointestinal disorders
  • gut–brain signaling mechanisms underlying the control of appetite and feeding in health and disease
  • influence of nutrient-related gut–brain signals on affective and cognitive processes in health and disease
  • influence of gut microbiota composition and function on psychobiological processes in health and disease, and identification of the microbiota–gut–brain signaling mechanisms underlying these relationships

Assoc. Prof. Dr. Lukas Van Oudenhove
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.

Keywords

  • gut–brain axis
  • microbiota
  • nutrients
  • functional gastrointestinal disorders
  • metabolic hormones

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Related Special Issue

Published Papers (8 papers)

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Research

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15 pages, 1918 KiB  
Article
Intestinal Microbiome in Irritable Bowel Syndrome before and after Gut-Directed Hypnotherapy
by Johannes Peter, Camille Fournier, Bettina Keip, Nina Rittershaus, Nicola Stephanou-Rieser, Marija Durdevic, Clemens Dejaco, Maria Michalski and Gabriele Moser
Int. J. Mol. Sci. 2018, 19(11), 3619; https://doi.org/10.3390/ijms19113619 - 16 Nov 2018
Cited by 28 | Viewed by 7003
Abstract
Irritable bowel syndrome (IBS) is a disorder with brain-gut-microbiome alterations. Gut-directed hypnotherapy (GHT) has been shown to improve quality of life and symptoms in IBS. This therapy targets psychological coping, central nervous processing and brain-gut interaction. Studies have also demonstrated effects of hypnosis [...] Read more.
Irritable bowel syndrome (IBS) is a disorder with brain-gut-microbiome alterations. Gut-directed hypnotherapy (GHT) has been shown to improve quality of life and symptoms in IBS. This therapy targets psychological coping, central nervous processing and brain-gut interaction. Studies have also demonstrated effects of hypnosis on intestinal transit and the mucosal immune system. So far, no study has examined the effect of GHT on the intestinal microbiome. This study aimed at examining microbial composition, IBS symptoms, and psychological distress before and after GHT. Methods: Fecal samples were collected from 38 IBS patients (Rome-III criteria, mean age 44 years, 27 female, 11 male, 22 diarrhea-dominant, 12 alternating-type and 4 constipation-dominant IBS) before and after 10 weekly group sessions of GHT. Assessments in psychological (perceived stress, PSQ; psychological distress, HADS-D; quality of life, visual analogue scales) and IBS symptom-related variables (IBS severity, IBS-SSS; single symptoms, visual analogue scales) were performed with validated questionnaires. Fecal samples underwent microbial 16S rRNA analyses (regions V1–2). Results: Microbial alpha diversity was stable before and after GHT (chao1 2591 ± 548 vs. 2581 ± 539, p = 0.92). No significant differences were found in relative bacterial abundances but trends of reduced abundance of Lachnospiraceae 32.18 (4.14–39.89) Median (Q1–Q3) vs. 28.11 (22.85; 35.55) and Firmicutes: Bacteroidetes ratio after GHT were observable. Significant reductions in symptom severity (323 (266–371) vs. 264 (191–331), p = 0.001) and psychological distress 17.0 (12.6–21.8) vs. 12.0 (8.3–18.0), p = 0.001, and increased well-being were found after GHT. Adequate relief after therapy was reported by 32 (84%) patients. Conclusion: Reductions in IBS symptoms and psychological burden were observed after gut-directed hypnotherapy, but only small changes were found in intestinal microbiota composition. The findings suggest that hypnosis may act by central nervous impact and other factors largely independent from microbiota composition modulating the brain-gut axis, possibly alterations in vagus nerve functioning and microbiota metabolism. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
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Review

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13 pages, 280 KiB  
Review
Advances in Imaging Specific Mediators of Inflammatory Bowel Disease
by Nicole Dmochowska, Hannah R. Wardill and Patrick A. Hughes
Int. J. Mol. Sci. 2018, 19(9), 2471; https://doi.org/10.3390/ijms19092471 - 21 Aug 2018
Cited by 34 | Viewed by 4497
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown, but it is thought to involve a hypersensitive immune response to environmental antigens, including the microbiota. Diagnosis and monitoring of [...] Read more.
Inflammatory bowel disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown, but it is thought to involve a hypersensitive immune response to environmental antigens, including the microbiota. Diagnosis and monitoring of IBD is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) of inflammatory mediators, and how these developments may be applied to the microbiota. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
15 pages, 281 KiB  
Review
Cognitive Impairment and Celiac Disease: Is Transcranial Magnetic Stimulation a Trait d’Union between Gut and Brain?
by Giuseppe Lanza, Rita Bella, Mariagiovanna Cantone, Giovanni Pennisi, Raffaele Ferri and Manuela Pennisi
Int. J. Mol. Sci. 2018, 19(8), 2243; https://doi.org/10.3390/ijms19082243 - 31 Jul 2018
Cited by 35 | Viewed by 6690
Abstract
Celiac disease is a systemic disorder with multifactorial pathogenesis and multifaceted symptomatology. In response to gluten exposure, a significant part of the general population produces antibodies that have been hypothesized to be deleterious to the brain. Among the well-known neurological manifestations, adult celiac [...] Read more.
Celiac disease is a systemic disorder with multifactorial pathogenesis and multifaceted symptomatology. In response to gluten exposure, a significant part of the general population produces antibodies that have been hypothesized to be deleterious to the brain. Among the well-known neurological manifestations, adult celiac patients often complain cognitive symptoms, ranging from the so-called “brain fog” till an overt dementia. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that can contribute to the assessment and monitoring of celiac patients, even in those without a clear neurological involvement. The studies here reviewed seem to converge on an impaired central motor conductivity and a “hyperexcitable celiac brain” to TMS, which partially reverts back after a long-term gluten restriction. Notably, a clear hyperexcitability is a stably reported feature of both degenerative and vascular dementia. Therefore, given its potential neuroprotective effect, the gluten-free diet should be introduced as early as possible, although the overall response of neurological symptoms (and cognition in particular) is still controversial. Identifying new and possibly modifiable risk factors may be of crucial importance for patients, clinicians, and researchers. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
59 pages, 2078 KiB  
Review
Enteric Microbiota–Gut–Brain Axis from the Perspective of Nuclear Receptors
by Kalina Duszka and Walter Wahli
Int. J. Mol. Sci. 2018, 19(8), 2210; https://doi.org/10.3390/ijms19082210 - 28 Jul 2018
Cited by 23 | Viewed by 10234
Abstract
Nuclear receptors (NRs) play a key role in regulating virtually all body functions, thus maintaining a healthy operating body with all its complex systems. Recently, gut microbiota emerged as major factor contributing to the health of the whole organism. Enteric bacteria have multiple [...] Read more.
Nuclear receptors (NRs) play a key role in regulating virtually all body functions, thus maintaining a healthy operating body with all its complex systems. Recently, gut microbiota emerged as major factor contributing to the health of the whole organism. Enteric bacteria have multiple ways to influence their host and several of them involve communication with the brain. Mounting evidence of cooperation between gut flora and NRs is already available. However, the full potential of the microbiota interconnection with NRs remains to be uncovered. Herewith, we present the current state of knowledge on the multifaceted roles of NRs in the enteric microbiota–gut–brain axis. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
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16 pages, 1644 KiB  
Review
The Expensive-Tissue Hypothesis in Vertebrates: Gut Microbiota Effect, a Review
by Chun Hua Huang, Xin Yu and Wen Bo Liao
Int. J. Mol. Sci. 2018, 19(6), 1792; https://doi.org/10.3390/ijms19061792 - 17 Jun 2018
Cited by 22 | Viewed by 8986
Abstract
The gut microbiota is integral to an organism’s digestive structure and has been shown to play an important role in producing substrates for gluconeogenesis and energy production, vasodilator, and gut motility. Numerous studies have demonstrated that variation in diet types is associated with [...] Read more.
The gut microbiota is integral to an organism’s digestive structure and has been shown to play an important role in producing substrates for gluconeogenesis and energy production, vasodilator, and gut motility. Numerous studies have demonstrated that variation in diet types is associated with the abundance and diversity of the gut microbiota, a relationship that plays a significant role in nutrient absorption and affects gut size. The Expensive-Tissue Hypothesis states (ETH) that the metabolic requirement of relatively large brains is offset by a corresponding reduction of the other tissues, such as gut size. However, how the trade-off between gut size and brain size in vertebrates is associated with the gut microbiota through metabolic requirements still remains unexplored. Here, we review research relating to and discuss the potential influence of gut microbiota on the ETH. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
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13 pages, 865 KiB  
Review
Phoenixin—A Pleiotropic Gut-Brain Peptide
by Martha A. Schalla and Andreas Stengel
Int. J. Mol. Sci. 2018, 19(6), 1726; https://doi.org/10.3390/ijms19061726 - 11 Jun 2018
Cited by 29 | Viewed by 7006
Abstract
Phoenixin is a recently discovered brain peptide initially thought to be restricted to reproductive functions. The subsequent identification of phoenixin’s expression in peripheral tissues was accompanied by the description of several other actions of this hormone, such as effects on behavior, sensory perception, [...] Read more.
Phoenixin is a recently discovered brain peptide initially thought to be restricted to reproductive functions. The subsequent identification of phoenixin’s expression in peripheral tissues was accompanied by the description of several other actions of this hormone, such as effects on behavior, sensory perception, memory retention, the cardiovascular system as well as food intake, pointing towards a pleiotropic role of this peptide. The present review will discuss the present knowledge on phoenixin and the signaling involved as well as highlight gaps in knowledge to stimulate further research. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
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16 pages, 459 KiB  
Review
Recognizing Depression from the Microbiota–Gut–Brain Axis
by Shan Liang, Xiaoli Wu, Xu Hu, Tao Wang and Feng Jin
Int. J. Mol. Sci. 2018, 19(6), 1592; https://doi.org/10.3390/ijms19061592 - 29 May 2018
Cited by 228 | Viewed by 47421
Abstract
Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain–gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs [...] Read more.
Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain–gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota–gut–brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain–gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
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Other

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4 pages, 175 KiB  
Commentary
The Perturbance of Microbiome and Gut-Brain Axis in Autism Spectrum Disorders
by Greta Fowlie, Nicholas Cohen and Xue Ming
Int. J. Mol. Sci. 2018, 19(8), 2251; https://doi.org/10.3390/ijms19082251 - 1 Aug 2018
Cited by 65 | Viewed by 15067
Abstract
Gastrointestinal problems have been documented in Autism Spectrum Disorder (ASD). Studies have found that these disturbances may be associated with an altered gut microbiome in ASD. Furthermore, in ASD, these alterations are implicated in increased gut permeability, or “leaky gut”, which allows bacterial [...] Read more.
Gastrointestinal problems have been documented in Autism Spectrum Disorder (ASD). Studies have found that these disturbances may be associated with an altered gut microbiome in ASD. Furthermore, in ASD, these alterations are implicated in increased gut permeability, or “leaky gut”, which allows bacterial metabolites to cross the gut barrier, impacting neurodevelopment during early childhood in susceptible subjects by way of gut-brain axis. In our review, we will discuss the interaction of gut microbiota and brain development in ASD and the signaling mechanisms underlying this interaction. We will also explore the potential for treatment of ASD by targeting the microbiome with probiotics. Finally, this paper will attempt to provide significance to the aggregation of the research in this area of research; providing our interpretations and assessments of future of this field. Full article
(This article belongs to the Special Issue The (Microbiota)–Gut–Brain Axis: Hype or Revolution?)
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