Review
Neurosciences
Xinnian Wang, Ruijin Tang, Zhen Wei, Yang Zhan, Jianping Lu, Zhiling Li
Summary: Gastrointestinal disorders frequently coexist with autism spectrum disorder (ASD), and the severity of core behavioral deficits in autism is closely related to abnormalities in these issues. The enteric nervous system (ENS) plays a vital role in regulating gut functions, including gastrointestinal motility. Dysfunctional wiring in the ENS not only leads to various gastrointestinal issues, but also correlates with an increasing number of central nervous system (CNS) disorders, such as ASD. However, it remains unclear whether the gastrointestinal dysfunctions are a consequence of ASD or if they directly contribute to its pathogenesis. This review focuses on the deficits in the ENS associated with ASD, highlights high-risk genes for ASD expressed in the gut and implicated in gastrointestinal dysfunction, and provides an overview of environmental factors associated with the gastrointestinal tract in individuals with autism.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Environmental Sciences
Jing Wang, Xinyao Meng, Chenzhao Feng, Jun Xiao, Xiang Zhao, Bo Xiong, Jiexiong Feng
Summary: Hirschsprung disease (HSCR) is a congenital disease characterized by a deficiency of enteric neurons, with genetic and environmental factors playing a role. Research suggests that the UV filter component BP-3 may inhibit the development of the enteric nervous system (ENS) through modulation of the MAPK/ERK signaling pathway. These findings provide insights into potential mechanisms for HSCR development and suggest therapeutic targets for intervention.
Article
Genetics & Heredity
Keqiang Liu, Ru Chen, Minzhong Zhang, Yiming Gong, Yong Wang, Wei Cai
Summary: Variants in the ERBB3 gene can lead to different disease phenotypes, including lethal congenital contracture syndrome and evident intestinal dysmotility. These findings help to better characterize the ERBB3-related phenotype spectrum, and reveal phenotypic variability caused by ERBB3 deficiency among different individuals.
Article
Infectious Diseases
Giulia Bernabe, Mahmoud Elsayed Mosaad Shalata, Veronica Zatta, Massimo Bellato, Andrea Porzionato, Ignazio Castagliuolo, Paola Brun
Summary: The side effects of antibiotic treatment are directly related to intestinal dysbiosis. This study examined the long-term effects of antibiotic-induced dysbiosis on the enteric nervous system and the impact of spontaneous restoration of gut microbiota on gastrointestinal functions. Two weeks of antibiotic treatment significantly altered gut microbial composition, and some bacterial genera did not regain their abundance after six weeks of discontinuation.
Article
Medicine, Research & Experimental
Yun Wang, Xinyu Xu, Lin Lin
Summary: The present study investigated the effects of prucalopride on intestinal motility in rats with diabetes mellitus by promoting the regeneration of the enteric nervous system. The results showed that prucalopride significantly shortened the colonic transit time in diabetic rats and increased the expression levels of Nestin, GFAP, SOX10, HuD, and PGP9.5.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Jackson L. K. Yip, Gayathri K. Balasuriya, Sarah J. Spencer, Elisa L. Hill-Yardin
Summary: Mice and rats have fundamental differences in colon motility and response to inhibition of nitric oxide neurotransmitter, making them important animal models for different questions in gastrointestinal research.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Tinh Thi Nguyen, Peter Baumann, Oliver Tuescher, Sandra Schick, Kristina Endres
Summary: The gut and the brain communicate through various channels and interactions, collectively known as the gut-brain axis. The aging of the enteric nervous system (ENS) in the gut can lead to gastrointestinal dysfunction and contribute to age-related diseases of the brain. Understanding the mechanisms of the aging ENS can provide insights into the diagnosis and treatment of neurodegenerative diseases like Alzheimer's and Parkinson's.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Justine Blin, Camille Gautier, Philippe Aubert, Tony Durand, Thibauld Oullier, Laetitia Aymeric, Philippe Naveilhan, Damien Masson, Michel Neunlist, Kalyane Bach-Ngohou
Summary: Repeated acute stress (RASt) is associated with gastrointestinal dysfunctions. This study found that the cholinergic component in the enteric nervous system (ENS) plays a role in these dysfunctions, possibly through the glucocorticoid receptor (GR) system. The use of a GR-specific antagonist can prevent the effects on colonic acetylcholine levels and motility.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Virology
Yaqian Li, Qiuyu Chen, Liwei Wang, Xin Chen, Bangmao Wang, Weilong Zhong
Summary: Gastrointestinal motility disorders are closely related to viral infections of the enteric nervous system. Viruses can infect the enteric nervous system through various means and cause symptoms such as abdominal pain and diarrhea. Studies have found that viruses are a cause of some gastrointestinal motility disorders.
Article
Gastroenterology & Hepatology
Crystal Woods, Amanda R. Flockton, Laurie E. Wallace, Catherine M. Keenan, Wendy B. Macklin, Keith A. Sharkey, Jaime Belkind-Gerson
Summary: Proteolipid protein 1 (Plp1) is highly expressed in enteric glia and plays a regulatory role in gut motility and barrier function, possibly through the Erk1/2 pathway. The absence of myelin in the enteric nervous system suggests another role for Plp1 in the gut.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2023)
Article
Immunology
Nabil Parkar, Julie E. Dalziel, Nick J. Spencer, Patrick Janssen, Warren C. McNabb, Wayne Young
Summary: Gastrointestinal (GI) motility relies on the enteric nervous system (ENS) and is crucial for digestion. Dysfunction in the ENS can lead to constipation. Animal models have been developed to mimic constipation symptoms through pharmacological manipulations, and studies have shown an association between altered GI motility and gut microbial population. However, little is known about the changes in gut microbiota resulting from slowed GI motility induced by medication, and the current understanding is based on studies using faecal samples which do not accurately represent the intestinal microbiome. This study aimed to investigate how delayed GI transit, caused by opioid receptor agonism in the ENS, affects caecal microbiota composition, and the results showed significant differences in microbial composition between treatment groups, with Bacteroides being relatively abundant in the group with slowed GI transit.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Wael N. El-Nachef, Claire Hu, Marianne E. Bronner
Summary: Imaging and quantifying all enteric neurons within the adult zebrafish intestine is possible, and a positive correlation between total enteric neuron number and intestinal length has been demonstrated in this study. This technique will facilitate future studies of enteric neuropathies and ENS structure in animal models and potentially in biopsied tissue samples.
NEUROGASTROENTEROLOGY AND MOTILITY
(2022)
Article
Cell Biology
Yan-Jiao Lu, Wen-Wen Yu, Meng-Meng Cui, Xian-Xian Yu, Huan-Lei Song, Mei-Rong Bai, Wen-Jie Wu, Bei-Lin Gu, Jun Wang, Wei Cai, Xun Chu
Summary: Common variants of DSCAM were associated with HSCR risk in the Han Chinese population, while common variants of BACE2 were not. Knockdown of both dscams and bace2 in zebrafish resulted in reduced enteric neurons in the hindgut, while overexpression of DSCAM and BACE2 did not affect neuron number in zebrafish hindgut.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Audrey Inge Schytz Andersen-Civil, Rajlakshmi Anjan Sawale, Gilles Claude Vanwalleghem
Summary: Autism spectrum disorders (ASD), affecting about 1% of the population, are strongly associated with gastrointestinal diseases, leading to deficits in quality of life. The development of ASD involves multiple factors, and dysregulation of gut microbiota and gut barrier integrity may play a crucial role. However, limited research has investigated the impact of the enteric nervous system (ENS) and intestinal mucosal immune factors on ASD-related intestinal disorders. This review assesses the regulation and interactions among enteric immune cells, gut microbiota, and ENS in ASD models, and highlights the potential of zebrafish as a valuable model for studying ASD pathogenesis.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Review
Immunology
Franze Progatzky, Vassilis Pachnis
Summary: This article reviews recent literature on the roles of enteric glial cells in intestinal immunity and tissue homeostasis.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Pieter Vanden Berghe
Article
Anatomy & Morphology
Samuel Van Remoortel, Lana Lambeets, Jean-Pierre Timmermans
Summary: Mrgprs, a new family of Rhodopsin A-like G protein-coupled receptors, have been shown to play a critical role in itch, pain, and the inflammatory/allergic responses in the skin. Their role is not limited to the skin but extends to other mucosal surfaces. In the gastrointestinal tract, Mrgprs are emerging as novel sensory pathways associated with health and disease, closely linked to the gut's immune system.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Derick Yongabi, Mehran Khorshid, Patricia Losada-Perez, Soroush Bakhshi Sichani, Stijn Jooken, Wouter Stilman, Florian Thesseling, Tobie Martens, Toon Van Thillo, Kevin Verstrepen, Peter Dedecker, Pieter Vanden Berghe, Minne Paul Lettinga, Carmen Bartic, Peter Lieberzeit, Michael J. Schoning, Ronald Thoelen, Marc Fransen, Michael Wubbenhorst, Patrick Wagner
Summary: In this study, a fast and facile label- and receptor-free method for cell characterization is proposed, using the natural response of cells to mild thermal stimuli. The time-patterns of synchronized and spontaneous cell detachment provide cell-specific indicators that can distinguish different cell types.
Article
Clinical Neurology
Wenting Guo, Haibo Wang, Arun Kumar Tharkeshwar, Julien Couthouis, Elke Braems, Pegah Masrori, Evelien Van Schoor, Yannan Fan, Karan Ahuja, Matthieu Moisse, Maarten Jacquemyn, Rodrigo Furtado Madeiro da Costa, Madhavsai Gajjar, Sriram Balusu, Tine Tricot, Laura Fumagalli, Nicole Hersmus, Rekin's Janky, Francis Impens, Pieter Vanden Berghe, Ritchie Ho, Dietmar Rudolf Thal, Rik Vandenberghe, Muralidhar L. Hegde, Siddharthan Chandran, Bart De Strooper, Dirk Daelemans, Philip Van Damme, Ludo Van den Bosch, Catherine Verfaillie
Summary: In this study, we identified NEK6 as a novel therapeutic target for C9orf72 FTD/ALS by performing a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell-derived cortical neurons. NEK6 was found to regulate poly(PR)-mediated p53-related DNA damage.
ALZHEIMERS & DEMENTIA
(2023)
Article
Gastroenterology & Hepatology
Zhiling Li, Werend Boesmans, Youcef Kazwiny, Marlene M. Hao, Pieter Vanden Berghe
Summary: Live calcium imaging is a valuable tool for simultaneous analysis of neuronal activity. This study investigated how enteric neurons respond to different modes of depolarization using electrophysiology and calcium imaging techniques. The research found that single action potentials can elicit calcium transients in both AH-neurons and S-neurons, and nicotinic acetylcholine receptor stimulation can be used to distinguish between these two classes.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Surgery
Sander Van Hoof, Toon Sels, Eveline Patteet, Tom Hendrickx, Sylvie Van den Broeck, Guy Hubens, Niels Komen
Summary: This study investigated the prevalence of functional complaints and quality of life after Hartmann's reversal surgery. The results showed that 32.8% of patients reported LARS-like symptoms, and 25% had significant COREFO scores. Higher LARS and COREFO scores were significantly associated with worse global quality of life and several quality of life domain scores.
AMERICAN JOURNAL OF SURGERY
(2023)
Article
Multidisciplinary Sciences
Valerie Van Steenbergen, Flavie Lavoie-Cardinal, Youcef Kazwiny, Marianna Decet, Tobie Martens, Patrik Verstreken, Werend Boesmans, Paul De Koninck, Pieter Vanden Berghe
Summary: The correct distribution of organelles and vesicles in cells is crucial for cell functioning. In polarized cells such as neurons, the transport of mitochondria, which play a key role in producing energy and buffering calcium, is especially important. This study found that the molecular conformation of tubulin affects mitochondrial transport in neurons. The position of a mitochondrion within or at the rim of a microtubule bundle determines the impact of tubulin conformation on mitochondrial transport.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Anatomy & Morphology
Jean-Pierre Timmermans
Summary: This article presents an introductory comment and overview of the autonomic nervous system research in Eastern Europe, with a focus on its innervation of the gastrointestinal tract and cardiovascular system. It also provides a selected overview of notable papers on these topics published in The Anatomical Record since 1906.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Anatomy & Morphology
Inge Brouns, Dirk Adriaensen, Jean-Pierre Timmermans
Summary: Exciting new imaging and molecular tools, combined with state-of-the-art genetically modified mouse models, have recently boosted interest in pulmonary (vagal) sensory pathway investigations. In addition, the review highlights the importance of studying the cellular and neuronal components of the pulmonary neuroepithelial bodies (NEBs) microenvironment (NEB ME) in mice, as it plays a crucial role in the mechano- and chemosensory potential of airways and lungs. Furthermore, the presence of different types of stem cells in the NEB ME and their potential role in lung pathogenesis or pathobiology is also discussed.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Cell Biology
Samuel Van Remoortel, Lana Lambeets, Heiko De Schepper, Jean-Pierre Timmermans
Summary: In recent years, it has been discovered that the family of Mas-related G protein-coupled receptors (MRGPRs) plays a crucial role in neuro-immune communication in the skin. However, the expression of MRGPRs at other mucosal surfaces remains poorly understood. This study aimed to investigate the expression of MRGPRs in mucosal biopsies of the human gastrointestinal (GI) tract. The results showed that MRGPRF mRNA was the only detectable member of the MRGPR family expressed in human mucosal biopsies of the terminal ileum and sigmoid colon. Immunohistochemical analysis revealed that MRGPRF was specifically expressed in mucosal entero-endocrine cells (EECs).
CELL AND TISSUE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Maria Francesca Viola, Marta Chavero-Pieres, Elodie Modave, Marcello Delfini, Nathalie Stakenborg, Maria Cuende Estevez, Naomi Fabre, Iris Appeltans, Tobie Martens, Katy Vandereyken, Hannah Theobald, Jens Van Herck, Philippe Petry, Simon Verheijden, Sebastiaan De Schepper, Alejandro Sifrim, Zhaoyuan Liu, Florent Ginhoux, Mohamad Azhar, Andreas Schlitzer, Gianluca Matteoli, Katrin Kierdorf, Marco Prinz, Pieter Vanden Berghe, Thierry Voet, Guy Boeckxstaens
Summary: Development and maturation of the enteric nervous system (ENS) relies on the actions of resident macrophages, which prune synapses and phagocytose enteric neurons in early life. After weaning, these macrophages continue to interact closely with the ENS and acquire a neurosupportive phenotype. This interaction is mediated by transforming growth factor-beta produced by the ENS, and disruption of this communication leads to loss of enteric neurons and altered intestinal transit.
Correction
Multidisciplinary Sciences
Franziska Bierbuesse, Anais C. Bourges, Vincent Gielen, Viola Monkemoller, Wim Vandenberg, Yi Shen, Johan Hofkens, Pieter Vanden Berghe, Robert E. Campbell, Benjamien Moeyaert, Peter Dedecker
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Thomas Plum, Rebecca Binzberger, Robin Thiele, Fuwei Shang, Daniel Postrach, Candice Fung, Marina Fortea, Nathalie Stakenborg, Zheng Wang, Anke Tappe-Theodor, Tanja Poth, Duncan A. A. MacLaren, Guy Boeckxstaens, Rohini Kuner, Claudia Pitzer, Hannah Monyer, Cuiyan Xin, Joseph V. Bonventre, Satoshi Tanaka, David Voehringer, Pieter Vanden Berghe, Jessica Strid, Thorsten B. Feyerabend, Hans-Reimer Rodewald
Summary: The physiological functions of mast cells are not well understood. Mast cells are involved in type 2 immunity and promote allergic diseases through the interaction with immunoglobulin E (IgE). However, allergic symptoms may also facilitate the elimination of allergens, toxins, and parasites and trigger future antigen avoidance. In this study, mast cells were found to be crucial for antigen-specific avoidance behavior in inbred mice. This behavior prevented immune activation and inflammation in the stomach and small intestine. Antigen avoidance was dependent on IgE and regulated by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells quickly detected the ingestion of antigens. Multiple signaling pathways between mast cells and the brain were identified. Inhibition of leukotriene synthesis impaired avoidance, but no single pathway interruption completely abolished it, suggesting complex regulation. Overall, antigen avoidance mediated by mast cells may play an important role in preventing immunopathology and repeated ingestion of toxins.
Article
Biology
Debby Van Dam, Femke Valkenburg, Kristof Van Kolen, Isabel Pintelon, Jean-Pierre Timmermans, Peter Paul De Deyn
Summary: The tau protein dysfunction is a core feature of neurodegenerative diseases, and mouse models expressing mutated tau protein associated with FTDP-17 can mimic some aspects of the disease. Our study demonstrates the validity of these models in replicating the pathology and symptoms of FTDP-17.
Article
Gastroenterology & Hepatology
Denise van der Graaff, Shivani Chotkoe, Benedicte De Winter, Joris De Man, Christophe Casteleyn, Jean-Pierre Timmermans, Isabel Pintelon, Luisa Vonghia, Wilhelmus J. Kwanten, Sven Francque
Summary: In non-alcoholic fatty liver disease (NAFLD), hepatic blood flow is impaired and the blood pressure in the liver blood vessels is increased as a result of an increased response of the liver vasculature to vasoconstrictors. Using drugs to block the constriction of the intrahepatic vasculature, the resistance of the liver blood vessels decreases and the increased portal pressure is reduced. Moreover, blocking the vasoconstrictive endothelin-1 pathway restored parenchymal architecture and reduced disease severity.