scholarly journals The Gut-Brain Axis in Inflammatory Bowel Disease—Current and Future Perspectives

2021 ◽  
Vol 22 (16) ◽  
pp. 8870
Author(s):  
Claudia Günther ◽  
Veit Rothhammer ◽  
Marisa Karow ◽  
Markus Neurath ◽  
Beate Winner
Keyword(s):  
Brain Function ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Sequence Of Events ◽  
Disease Mechanisms ◽  
Bidirectional Communication ◽  
Bowel Diseases ◽  
The Central Nervous System ◽  
Inflammatory Bowel ◽  
Human Specific

The gut–brain axis is a bidirectional communication system driven by neural, hormonal, metabolic, immunological, and microbial signals. Signaling events from the gut can modulate brain function and recent evidence suggests that the gut–brain axis may play a pivotal role in linking gastrointestinal and neurological diseases. Accordingly, accumulating evidence has suggested a link between inflammatory bowel diseases (IBDs) and neurodegenerative, as well as neuroinflammatory diseases. In this context, clinical, epidemiological and experimental data have demonstrated that IBD predisposes a person to pathologies of the central nervous system (CNS). Likewise, a number of neurological disorders are associated with changes in the intestinal environment, which are indicative for disease-mediated gut–brain inter-organ communication. Although this axis was identified more than 20 years ago, the sequence of events and underlying molecular mechanisms are poorly defined. The emergence of precision medicine has uncovered the need to take into account non-intestinal symptoms in the context of IBD that could offer the opportunity to tailor therapies to individual patients. The aim of this review is to highlight recent findings supporting the clinical and biological link between the gut and brain, as well as its clinical significance for IBD as well as neurodegeneration and neuroinflammation. Finally, we focus on novel human-specific preclinical models that will help uncover disease mechanisms to better understand and modulate the function of this complex system.

scholarly journals Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis

2020 ◽  
Vol 21 (9) ◽  
pp. 3062 ◽  
Author(s):  
Takehiro Hirano ◽  
Daisuke Hirayama ◽  
Kohei Wagatsuma ◽  
Tsukasa Yamakawa ◽  
Yoshihiro Yokoyama ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
T Helper 17 ◽  
Colon Inflammation ◽  
Immunological Mechanisms ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Cumulative Rate ◽  
T Helper 17 Cell ◽  
Inflammatory Bowel

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.

Gut–brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function

2018 ◽  
Vol 94 (1114) ◽  
pp. 446-452 ◽  
Author(s):  
Borros M Arneth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Function ◽  
Well Being ◽  
Immune System Activation ◽  
Published Evidence ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Intestinal Functions ◽  
The Brain

BackgroundThe gut–brain axis facilitates a critical bidirectional link and communication between the brain and the gut. Recent studies have highlighted the significance of interactions in the gut–brain axis, with a particular focus on intestinal functions, the nervous system and the brain. Furthermore, researchers have examined the effects of the gut microbiome on mental health and psychiatric well-being.The present study reviewed published evidence to explore the concept of the gut–brain axis.AimsThis systematic review investigated the relationship between human brain function and the gut–brain axis.MethodsTo achieve these objectives, peer-reviewed articles on the gut–brain axis were identified in various electronic databases, including PubMed, MEDLINE, CIHAHL, Web of Science and PsycINFO.ResultsData obtained from previous studies showed that the gut–brain axis links various peripheral intestinal functions to brain centres through a broad range of processes and pathways, such as endocrine signalling and immune system activation. Researchers have found that the vagus nerve drives bidirectional communication between the various systems in the gut–brain axis. In humans, the signals are transmitted from the liminal environment to the central nervous system.ConclusionsThe communication that occurs in the gut–brain axis can alter brain function and trigger various psychiatric conditions, such as schizophrenia and depression. Thus, elucidation of the gut–brain axis is critical for the management of certain psychiatric and mental disorders.

scholarly journals Molecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases

2021 ◽  
Vol 22 (17) ◽  
pp. 9139
Author(s):  
Chang-Kee Hyun
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Bowel Diseases ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Pathological Feature ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver ◽  
Intestinal Immune System ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Despite considerable epidemiological evidence indicating comorbidity between metabolic disorders, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, as well as common pathophysiological features shared by these two categories of diseases, the relationship between their pathogenesis at molecular levels are not well described. Intestinal barrier dysfunction is a characteristic pathological feature of IBD, which also plays causal roles in the pathogenesis of chronic inflammatory metabolic disorders. Increased intestinal permeability is associated with a pro-inflammatory response of the intestinal immune system, possibly leading to the development of both diseases. In addition, dysregulated interactions between the gut microbiota and the host immunity have been found to contribute to immune-mediated disorders including the two diseases. In connection with disrupted gut microbial composition, alterations in gut microbiota-derived metabolites have also been shown to be closely related to the pathogeneses of both diseases. Focusing on these prominent pathophysiological features observed in both metabolic disorders and IBD, this review highlights and summarizes the molecular risk factors that may link between the pathogeneses of the two diseases, which is aimed at providing a comprehensive understanding of molecular mechanisms underlying their comorbidity.

The Molecular Biology of Inflammatory Bowel Diseases

2011 ◽  
Vol 39 (4) ◽  
pp. 1057-1060 ◽  
Author(s):  
Anthony P. Corfield ◽  
Heather M. Wallace ◽  
Chris S.J. Probert
Keyword(s):  
Gastrointestinal Tract ◽  
Animal Models ◽  
Molecular Biology ◽  
Inflammatory Bowel Diseases ◽  
Susceptibility Genes ◽  
Adaptive Responses ◽  
Molecular Features ◽  
Disease Mechanisms ◽  
Bowel Diseases ◽  
Inflammatory Bowel

IBDs (inflammatory bowel diseases) are a group of diseases affecting the gastrointestinal tract. The diseases are multifactorial and cover genetic aspects: susceptibility genes, innate and adaptive responses to inflammation, and structure and efficacy of the mucosal protective barrier. Animal models of IBD have been developed to gain further knowledge of the disease mechanisms. These topics form an overlapping background to enable an improved understanding of the molecular features of these diseases. A series of articles is presented based on the topics covered at the Biochemical Society Focused Meeting The Molecular Biology of Inflammatory Bowel Diseases.

scholarly journals Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 774
Author(s):  
Abigail R. Basson ◽  
Saleh Ahmed ◽  
Rawan Almutairi ◽  
Brian Seo ◽  
Fabio Cominelli
Keyword(s):  
Ulcerative Colitis ◽  
Intestinal Inflammation ◽  
Saturated Fat ◽  
Rodent Models ◽  
High Intake ◽  
Disease Mechanisms ◽  
Bowel Diseases ◽  
Disease Induction ◽  
Inflammatory Bowel ◽  
Refined Carbohydrates

Environmental factors, particularly diet, are considered central to the pathogenesis of the inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis. In particular, the Westernization of diet, characterized by high intake of animal protein, saturated fat, and refined carbohydrates, has been shown to contribute to the development and progression of IBD. During the last decade, soybean, as well as soy-derived bioactive compounds (e.g., isoflavones, phytosterols, Bowman-Birk inhibitors) have been increasingly investigated because of their anti-inflammatory properties in animal models of IBD. Herein we provide a scoping review of the most studied disease mechanisms associated with disease induction and progression in IBD rodent models after feeding of either the whole food or a bioactive present in soybean.

scholarly journals Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor

2021 ◽  
Author(s):  
Yan Wei ◽  
Lijia Chang ◽  
Kenji Hashimoto
Keyword(s):  
Psychiatric Disorders ◽  
Molecular Mechanisms ◽  
The United States ◽  
Racemic Mixture ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Resistant Depression ◽  
The Brain ◽  
Related Compounds

AbstractThe discovery of robust antidepressant actions exerted by the N-methyl-D-aspartate receptor (NMDAR) antagonist (R,S)-ketamine has been a crucial breakthrough in mood disorder research. (R,S)-ketamine is a racemic mixture of equal amounts of (R)-ketamine (arketamine) and (S)-ketamine (esketamine). In 2019, an esketamine nasal spray from Johnson & Johnson was approved in the United States of America and Europe for treatment-resistant depression. However, an increasing number of preclinical studies show that arketamine has greater potency and longer-lasting antidepressant-like effects than esketamine in rodents, despite the lower binding affinity of arketamine for the NMDAR. In clinical trials, non-ketamine NMDAR-related compounds did not exhibit ketamine-like robust antidepressant actions in patients with depression, despite these compounds showing antidepressant-like effects in rodents. Thus, the rodent data do not necessarily translate to humans due to the complexity of human psychiatric disorders. Collectively, the available studies indicate that it is unlikely that NMDAR plays a major role in the antidepressant action of (R,S)-ketamine and its enantiomers, although the precise molecular mechanisms underlying antidepressant actions of (R,S)-ketamine and its enantiomers remain unclear. In this paper, we review recent findings on the molecular mechanisms underlying the antidepressant actions of (R,S)-ketamine and its potent enantiomer arketamine. Furthermore, we discuss the possible role of the brain–gut–microbiota axis and brain–spleen axis in stress-related psychiatric disorders and in the antidepressant-like action of arketamine. Finally, we discuss the potential of arketamine as a treatment for cognitive impairment in psychiatric disorders, Parkinson’s disease, osteoporosis, inflammatory bowel diseases, and stroke.

scholarly journals Investigating host-microbiome interactions by droplet based microfluidics

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Alexandra S. Tauzin ◽  
Mariana Rangel Pereira ◽  
Liisa D. Van Vliet ◽  
Pierre-Yves Colin ◽  
Elisabeth Laville ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Molecular Mechanisms ◽  
Droplet Microfluidics ◽  
Mucosal Barrier ◽  
Screening Process ◽  
Genomic Libraries ◽  
Gut Colonization ◽  
Custom Made ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Despite the importance of the mucosal interface between microbiota and the host in gut homeostasis, little is known about the mechanisms of bacterial gut colonization, involving foraging for glycans produced by epithelial cells. The slow pace of progress toward understanding the underlying molecular mechanisms is largely due to the lack of efficient discovery tools, especially those targeting the uncultured fraction of the microbiota. Results Here, we introduce an ultra-high-throughput metagenomic approach based on droplet microfluidics, to screen fosmid libraries. Thousands of bacterial genomes can be covered in 1 h of work, with less than ten micrograms of substrate. Applied to the screening of the mucosal microbiota for β-N-acetylgalactosaminidase activity, this approach allowed the identification of pathways involved in the degradation of human gangliosides and milk oligosaccharides, the structural homologs of intestinal mucin glycans. These pathways, whose prevalence is associated with inflammatory bowel diseases, could be the result of horizontal gene transfers with Bacteroides species. Such pathways represent novel targets to study the microbiota-host interactions in the context of inflammatory bowel diseases, in which the integrity of the mucosal barrier is impaired. Conclusion By compartmentalizing experiments inside microfluidic droplets, this method speeds up and miniaturizes by several orders of magnitude the screening process compared to conventional approaches, to capture entire metabolic pathways from metagenomic libraries. The method is compatible with all types of (meta)genomic libraries, and employs a commercially available flow cytometer instead of a custom-made sorting system to detect intracellular or extracellular enzyme activities. This versatile and generic workflow will accelerate experimental exploration campaigns in functional metagenomics and holobiomics studies, to further decipher host-microbiota relationships.

scholarly journals CHIP as a therapeutic target for neurological diseases

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Shuo Zhang ◽  
Zheng-wei Hu ◽  
Cheng-yuan Mao ◽  
Chang-he Shi ◽  
Yu-ming Xu
Keyword(s):  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Critical Role ◽  
Interacting Protein ◽  
Ubiquitin E3 Ligase ◽  
Promising Therapeutic Target ◽  
Wide Range ◽  
Range Of Functions ◽  
The Central Nervous System

Abstract Carboxy-terminus of Hsc70-interacting protein (CHIP) functions both as a molecular co-chaperone and ubiquitin E3 ligase playing a critical role in modulating the degradation of numerous chaperone-bound proteins. To date, it has been implicated in the regulation of numerous biological functions, including misfolded-protein refolding, autophagy, immunity, and necroptosis. Moreover, the ubiquitous expression of CHIP in the central nervous system suggests that it may be implicated in a wide range of functions in neurological diseases. Several recent studies of our laboratory and other groups have highlighted the beneficial role of CHIP in the pathogenesis of several neurological diseases. The objective of this review is to discuss the possible molecular mechanisms that contribute to the pathogenesis of neurological diseases in which CHIP has a pivotal role, such as stroke, intracerebral hemorrhage, Alzheimer’s disease, Parkinson’s disease, and polyglutamine diseases; furthermore, CHIP mutations could also cause neurodegenerative diseases. Based on the available literature, CHIP overexpression could serve as a promising therapeutic target for several neurological diseases.

scholarly journals Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dickson Kofi Wiredu Ocansey ◽  
Bing Pei ◽  
Xinwei Xu ◽  
Lu Zhang ◽  
Chinasa Valerie Olovo ◽  
...  
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Wide Spectrum ◽  
Adaptive Immune System ◽  
Therapeutic Interventions ◽  
Complex Processes ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Recent studies reporting the intricate crosstalk between cellular and molecular mediators and the lymphatic endothelium in the development of inflammatory bowel diseases (IBD) suggest altered inflammatory cell drainage and lymphatic vasculature, implicating the lymphatic system as a player in the occurrence, development, and recurrence of intestinal diseases. This article aims to review recent data on the modulatory functions of cellular and molecular components of the IBD microenvironment on the lymphatic system, particularly lymphangiogenesis. It serves as a promising therapeutic target for IBD management and treatment. The interaction with gut microbiota is also explored. Main text Evidence shows that cells of the innate and adaptive immune system and certain non-immune cells participate in the complex processes of inflammatory-induced lymphangiogenesis through the secretion of a wide spectrum of molecular factors, which vary greatly among the various cells. Lymphangiogenesis enhances lymphatic fluid drainage, hence reduced infiltration of immunomodulatory cells and associated-inflammatory cytokines. Interestingly, some of the cellular mediators, including mast cells, neutrophils, basophils, monocytes, and lymphatic endothelial cells (LECs), are a source of lymphangiogenic molecules, and a target as they express specific receptors for lymphangiogenic factors. Conclusion The effective target of lymphangiogenesis is expected to provide novel therapeutic interventions for intestinal inflammatory conditions, including IBD, through both immune and non-immune cells and based on cellular and molecular mechanisms of lymphangiogenesis that facilitate inflammation resolution.

scholarly journals Medical management of Crohn’s disease: state of the art and future perspectives

2019 ◽  
Vol 13 (3) ◽  
pp. 152-160
Author(s):  
Fabio Salvatore Macaluso
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Molecular Mechanisms ◽  
Oral Route ◽  
New Drugs ◽  
Mediators Of Inflammation ◽  
Bowel Diseases ◽  
Intrinsic Complexity ◽  
Inflammatory Bowel

Over the past decade, the improvement in the understanding of the molecular mechanisms of Crohn’s disease (CD) led to the development of more targeted therapies, including biologics - i.e. monoclonal antibodies that selectively block key mediators of inflammation - and novel small molecule drugs - i.e. compounds with a molecular weight <1 kDa able to diffuse through cell membranes and then fit for the oral route of administration - which will enrich the therapeutic armamentarium of CD soon. In parallel with the expansion of the medical options, the therapeutic targets to be achieved in patients with CD have changed. In particular, we moved from the simple control of symptoms to more ambitious goals which aim to permanently extinguish the inflammation, even the subclinical one. As a consequence, the role of some of the conventional drugs which have been used in CD for several years, such as 5-aminosalicylates and conventional immunosuppressants, is becoming more limited in favor of these new drugs. This profound modification of CD therapy and the intrinsic complexity of the disease are relevant to the point that the management of inflammatory bowel diseases is gradually becoming a subspecialty in the field of gastroenterology or internal medicine.

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