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Meerschaert KA, Chiu IM. The gut-brain axis and pain signalling mechanisms in the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 2024:10.1038/s41575-024-01017-9. [PMID: 39578592 DOI: 10.1038/s41575-024-01017-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2024] [Indexed: 11/24/2024]
Abstract
Visceral pain is a major clinical problem and one of the most common reasons patients with gastrointestinal disorders seek medical help. Peripheral sensory neurons that innervate the gut can detect noxious stimuli and send signals to the central nervous system that are perceived as pain. There is a bidirectional communication network between the gastrointestinal tract and the nervous system that mediates pain through the gut-brain axis. Sensory neurons detect mechanical and chemical stimuli within the intestinal tissues, and receive signals from immune cells, epithelial cells and the gut microbiota, which results in peripheral sensitization and visceral pain. This Review focuses on molecular communication between these non-neuronal cell types and neurons in visceral pain. These bidirectional interactions can be dysregulated during gastrointestinal diseases to exacerbate visceral pain. We outline the anatomical pathways involved in pain processing in the gut and how cell-cell communication is integrated into this gut-brain axis. Understanding how bidirectional communication between the gut and nervous system is altered during disease could provide new therapeutic targets for treating visceral pain.
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Affiliation(s)
| | - Isaac M Chiu
- Department of Immunology, Harvard Medical School, Boston, MA, USA.
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2
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Leech T, Peiris M. Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis. J Gastroenterol 2024; 59:165-178. [PMID: 38221552 PMCID: PMC10904498 DOI: 10.1007/s00535-023-02065-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/30/2023] [Indexed: 01/16/2024]
Abstract
Gastro-oesophageal reflux disease (GORD) is a chronic condition characterised by visceral pain in the distal oesophagus. The current first-line treatment for GORD is proton pump inhibitors (PPIs), however, PPIs are ineffective in a large cohort of patients and long-term use may have adverse effects. Emerging evidence suggests that nerve fibre number and location are likely to play interrelated roles in nociception in the oesophagus of GORD patients. Simultaneously, alterations in cells of the oesophageal mucosa, namely epithelial cells, mast cells, dendritic cells, and T lymphocytes, have been a focus of GORD research for several years. The oesophagus of GORD patients exhibits both macro- and micro-inflammation as a response to chronic acidic reflux at the epithelium. In other conditions of the GI tract, such as IBS and IBD, well-characterised bidirectional processes between immune cells and mucosal nerve fibres contribute to pathogenesis and symptom generation. Sensory alterations in these conditions such as nerve fibre outgrowth and hypersensitivity can be driven by inflammatory processes, which promote visceral pain signalling. This review will examine what is currently known of the molecular pathways linking inflammation and sensory perception leading to the development of GORD symptoms and explore potentially relevant mechanisms in other GI regions which may indicate new areas in GORD research.
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Affiliation(s)
- Tom Leech
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK
| | - Madusha Peiris
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
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3
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Hesampour F, Bernstein CN, Ghia JE. Brain-Gut Axis: Invasive and Noninvasive Vagus Nerve Stimulation, Limitations, and Potential Therapeutic Approaches. Inflamm Bowel Dis 2024; 30:482-495. [PMID: 37738641 DOI: 10.1093/ibd/izad211] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Indexed: 09/24/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing condition with no known etiology and is characterized by disrupted gut homeostasis, chronic inflammation, and ulcerative lesions. Although current treatments can reduce disease activity, IBD frequently recurs once treatments are discontinued, indicating that treatments are ineffective in providing long-term remission. The lack of responsiveness and reluctance of some affected persons to take medications because of potential adverse effects has enhanced the need for novel therapeutic approaches. The vagus nerve (VN) is likely important in the pathogenesis of IBD, considering the decreased activity of the parasympathetic nervous system, especially the VN, and the impaired interaction between the enteric nervous system and central nervous system in patients with IBD. Vagus nerve stimulation (VNS) has demonstrated anti-inflammatory effects in various inflammatory disorders, including IBD, by inhibiting the production of inflammatory cytokines by immune cells. It has been suggested that stimulating the vagus nerve to induce its anti-inflammatory effects may be a potential therapeutic approach for IBD. Noninvasive techniques for VNS have been developed. Considering the importance of VN function in the brain-gut axis, VNS is a promising treatment option for IBD. This review discusses the potential therapeutic advantages and drawbacks of VNS, particularly the use of noninvasive transcutaneous auricular vagus nerve stimulation.
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Affiliation(s)
| | - Charles N Bernstein
- Internal Medicine, University of Manitoba, Winnipeg, Canada
- Inflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, Winnipeg, Canada
| | - Jean-Eric Ghia
- Immunology, University of Manitoba, Winnipeg, Canada
- Internal Medicine, University of Manitoba, Winnipeg, Canada
- Inflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, Winnipeg, Canada
- Children's Hospital Research Institute of Manitoba, Winnipeg, Canada
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4
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Choi EL, Taheri N, Zhang Y, Matsumoto K, Hayashi Y. The critical role of muscularis macrophages in modulating the enteric nervous system function and gastrointestinal motility. J Smooth Muscle Res 2024; 60:1-9. [PMID: 38462479 PMCID: PMC10921093 DOI: 10.1540/jsmr.60.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/14/2024] [Indexed: 03/12/2024] Open
Abstract
Macrophages are the originators of inflammatory compounds, phagocytic purifiers in their local environment, and wound healing protectors in oxidative environments. They are molded by the tissue milieu they inhabit, with gastrointestinal (GI) muscularis macrophages (MMs) being a prime example. MMs are located in the muscular layer of the GI tract and contribute to muscle repair and maintenance of GI motility. MMs are often in close proximity to the enteric nervous system, specifically near the enteric neurons and interstitial cells of Cajal (ICCs). Consequently, the anti-inflammatory function of MMs corresponds to the development and maintenance of neural networks in the GI tract. The capacity of MMs to shift from anti-inflammatory to proinflammatory states may contribute to the inflammatory aspects of various GI diseases and disorders such as diabetic gastroparesis or postoperative ileus, functional disorders such as irritable bowel syndrome, and organic diseases such as inflammatory bowel disease. We reviewed the current knowledge of MMs and their influence on neighboring cells due to their important role in the GI tract.
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Affiliation(s)
- Egan L. Choi
- Graduate Research Education Program in the Department of
Physiology and Biomedical Engineering, Mayo Clinic Graduate School of Biomedical Sciences,
200 First Street SW, Rochester, MN 55905, USA
| | - Negar Taheri
- Research Fellow in the Department of Physiology and
Biomedical Engineering, Mayo Clinic School of Graduate Medical Education, 200 First Street
SW, Rochester, MN 55905, USA
| | - Yuebo Zhang
- Department of Physiology and Biomedical Engineering, Mayo
Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Kenjiro Matsumoto
- Laboratory of Pathophysiology, Faculty of Pharmaceutical
Sciences, Doshisha Woman’s College of Liberal Arts, Kodo, Kyotanabe City, Kyoto 610-0395,
Japan
| | - Yujiro Hayashi
- Department of Physiology and Biomedical Engineering, Mayo
Clinic, 200 First Street SW, Rochester, MN 55905, USA
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5
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Zhang X, Wang Y, Cai Z, Wan Z, Aihemaiti Y, Tu H. A gonadal gap junction INX-14/Notch GLP-1 signaling axis suppresses gut defense through an intestinal lysosome pathway. Front Immunol 2023; 14:1249436. [PMID: 37928537 PMCID: PMC10620905 DOI: 10.3389/fimmu.2023.1249436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 10/03/2023] [Indexed: 11/07/2023] Open
Abstract
Gap junctions mediate intercellular communications across cellular networks in the nervous and immune systems. Yet their roles in intestinal innate immunity are poorly understood. Here, we show that the gap junction/innexin subunit inx-14 acts in the C. elegans gonad to attenuate intestinal defenses to Pseudomonas aeruginosa PA14 infection through the PMK-1/p38 pathway. RNA-Seq analyses revealed that germline-specific inx-14 RNAi downregulated Notch/GLP-1 signaling, while lysosome and PMK-1/p38 pathways were upregulated. Consistently, disruption of inx-14 or glp-1 in the germline enhanced resistance to PA14 infection and upregulated lysosome and PMK-1/p38 activity. We show that lysosome signaling functions downstream of the INX-14/GLP-1 signaling axis and upstream of PMK-1/p38 pathway to facilitate intestinal defense. Our findings expand the understanding of the links between the reproductive system and intestinal defense, which may be evolutionarily conserved in higher organism.
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Affiliation(s)
| | | | | | | | | | - Haijun Tu
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, Changsha, Hunan, China
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6
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Giada A, Giulia G, Paola S, Silvia F. Characterization of prokineticin system in Crohn's disease pathophysiology and pain, and its modulation by alcohol abuse: A preclinical study. Biochim Biophys Acta Mol Basis Dis 2023:166791. [PMID: 37336367 DOI: 10.1016/j.bbadis.2023.166791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/21/2023] [Accepted: 06/14/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND Crohn's disease-(CD) pathogenesis is still unknown and chronic pain is a frequent symptom in CD-patients. Identifying novel therapeutic targets and predisposing factors is a primary goal. In this regard, prokineticin system-(PKS) appears a promising target. AIMS AND METHODS TNBS-model was used. DAI, abdominal and visceral pain, and muscle strength were monitored. CD-mice were sacrificed at two times (day 7 and 14 after TNBS) in order to identify PKS involvement in CD pathophysiology and pain. PKS characterization was performed in mesenteric lymph nodes-(MLN), colon, myenteric plexus-(MP), dorsal root ganglia-(DRGs) and spinal cord-(SC). Inflammation/neuroinflammation was also assessed in the same tissues. In order to evaluate alcohol abuse as a possible trigger for CD and its effect on PKS activation, naïve mice were administered (oral-gavage) with ethanol for 10 consecutive days. PKS as well as inflammation/neuroinflammation were evaluated in MLN, colon and MP. RESULTS TNBS treated-mice showed a rapid increase in DAI, abdominal/visceral hypersensitivity and a progressive strength loss. In all tissue analysed of CD-mice, a quick and significant increase of mRNA of PKs and PKRs was observed, associated with an increase of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) and macrophage/glia markers (iba1, CD11b and GFAP) levels. In alcohol abuse model, ethanol induced in colon and MP a significant PKS activation accompanied by inflammation/neuroinflammation. CONCLUSIONS We can assume that PKS may be involved in CD development and pain. Furthermore, alcohol appears to activate PKS and may be a trigger factor for CD.
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Affiliation(s)
- Amodeo Giada
- Dipartimento di Scienze Farmacologiche e Biomolecolari "Rodolfo Paoletti", University of Milan, Milan, Via Vanvitelli 32, 20129 Milano, Italy.
| | - Galimberti Giulia
- Dipartimento di Scienze Farmacologiche e Biomolecolari "Rodolfo Paoletti", University of Milan, Milan, Via Vanvitelli 32, 20129 Milano, Italy
| | - Sacerdote Paola
- Dipartimento di Scienze Farmacologiche e Biomolecolari "Rodolfo Paoletti", University of Milan, Milan, Via Vanvitelli 32, 20129 Milano, Italy
| | - Franchi Silvia
- Dipartimento di Scienze Farmacologiche e Biomolecolari "Rodolfo Paoletti", University of Milan, Milan, Via Vanvitelli 32, 20129 Milano, Italy
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Chen Y, Liu Z, Gong Y. Neuron-immunity communication: mechanism of neuroprotective effects in EGCG. Crit Rev Food Sci Nutr 2023; 64:9333-9352. [PMID: 37216484 DOI: 10.1080/10408398.2023.2212069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Epigallocatechin gallate (EGCG), a naturally occurring active ingredient unique to tea, has been shown to have neuroprotective potential. There is growing evidence of its potential advantages in the prevention and treatment of neuroinflammation, neurodegenerative diseases, and neurological damage. Neuroimmune communication is an important physiological mechanism in neurological diseases, including immune cell activation and response, cytokine delivery. EGCG shows great neuroprotective potential by modulating signals related to autoimmune response and improving communication between the nervous system and the immune system, effectively reducing the inflammatory state and neurological function. During neuroimmune communication, EGCG promotes the secretion of neurotrophic factors into the repair of damaged neurons, improves intestinal microenvironmental homeostasis, and ameliorates pathological phenotypes through molecular and cellular mechanisms related to the brain-gut axis. Here, we discuss the molecular and cellular mechanisms of inflammatory signaling exchange involving neuroimmune communication. We further emphasize that the neuroprotective role of EGCG is dependent on the modulatory role between immunity and neurology in neurologically related diseases.
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Affiliation(s)
- Ying Chen
- Key Laboratory of Tea Science of Ministry of Educatioxn, Changsha, China
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Changsha, China
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Educatioxn, Changsha, China
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Changsha, China
- Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Changsha, China
- Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha, China
| | - Yushun Gong
- Key Laboratory of Tea Science of Ministry of Educatioxn, Changsha, China
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Changsha, China
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Sharkey KA, Mawe GM. The enteric nervous system. Physiol Rev 2023; 103:1487-1564. [PMID: 36521049 PMCID: PMC9970663 DOI: 10.1152/physrev.00018.2022] [Citation(s) in RCA: 100] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 12/12/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022] Open
Abstract
Of all the organ systems in the body, the gastrointestinal tract is the most complicated in terms of the numbers of structures involved, each with different functions, and the numbers and types of signaling molecules utilized. The digestion of food and absorption of nutrients, electrolytes, and water occurs in a hostile luminal environment that contains a large and diverse microbiota. At the core of regulatory control of the digestive and defensive functions of the gastrointestinal tract is the enteric nervous system (ENS), a complex system of neurons and glia in the gut wall. In this review, we discuss 1) the intrinsic neural control of gut functions involved in digestion and 2) how the ENS interacts with the immune system, gut microbiota, and epithelium to maintain mucosal defense and barrier function. We highlight developments that have revolutionized our understanding of the physiology and pathophysiology of enteric neural control. These include a new understanding of the molecular architecture of the ENS, the organization and function of enteric motor circuits, and the roles of enteric glia. We explore the transduction of luminal stimuli by enteroendocrine cells, the regulation of intestinal barrier function by enteric neurons and glia, local immune control by the ENS, and the role of the gut microbiota in regulating the structure and function of the ENS. Multifunctional enteric neurons work together with enteric glial cells, macrophages, interstitial cells, and enteroendocrine cells integrating an array of signals to initiate outputs that are precisely regulated in space and time to control digestion and intestinal homeostasis.
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Affiliation(s)
- Keith A Sharkey
- Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Gary M Mawe
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, Vermont
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9
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Hanč P, Messou MA, Wang Y, von Andrian UH. Control of myeloid cell functions by nociceptors. Front Immunol 2023; 14:1127571. [PMID: 37006298 PMCID: PMC10064072 DOI: 10.3389/fimmu.2023.1127571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/23/2023] [Indexed: 03/19/2023] Open
Abstract
The immune system has evolved to protect the host from infectious agents, parasites, and tumor growth, and to ensure the maintenance of homeostasis. Similarly, the primary function of the somatosensory branch of the peripheral nervous system is to collect and interpret sensory information about the environment, allowing the organism to react to or avoid situations that could otherwise have deleterious effects. Consequently, a teleological argument can be made that it is of advantage for the two systems to cooperate and form an “integrated defense system” that benefits from the unique strengths of both subsystems. Indeed, nociceptors, sensory neurons that detect noxious stimuli and elicit the sensation of pain or itch, exhibit potent immunomodulatory capabilities. Depending on the context and the cellular identity of their communication partners, nociceptors can play both pro- or anti-inflammatory roles, promote tissue repair or aggravate inflammatory damage, improve resistance to pathogens or impair their clearance. In light of such variability, it is not surprising that the full extent of interactions between nociceptors and the immune system remains to be established. Nonetheless, the field of peripheral neuroimmunology is advancing at a rapid pace, and general rules that appear to govern the outcomes of such neuroimmune interactions are beginning to emerge. Thus, in this review, we summarize our current understanding of the interaction between nociceptors and, specifically, the myeloid cells of the innate immune system, while pointing out some of the outstanding questions and unresolved controversies in the field. We focus on such interactions within the densely innervated barrier tissues, which can serve as points of entry for infectious agents and, where known, highlight the molecular mechanisms underlying these interactions.
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Affiliation(s)
- Pavel Hanč
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
- *Correspondence: Pavel Hanč, ; Ulrich H. von Andrian,
| | - Marie-Angèle Messou
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
| | - Yidi Wang
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
| | - Ulrich H. von Andrian
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
- *Correspondence: Pavel Hanč, ; Ulrich H. von Andrian,
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10
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Lee YF, Wu MC, Ma KSK, Huang JY, Wei JCC. Association of early childhood constipation with the risk of autism spectrum disorder in Taiwan: Real-world evidence from a nationwide population-based cohort study. Front Psychiatry 2023; 14:1116239. [PMID: 37065891 PMCID: PMC10098334 DOI: 10.3389/fpsyt.2023.1116239] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 02/28/2023] [Indexed: 04/18/2023] Open
Abstract
Background Autism spectrum disorder (ASD) is a neurodevelopmental problem that presents with limited interests, repetitive behaviors, and deficits in reciprocal communication and social interactions. Mounting evidence indicates that an imbalanced gut microbiota contributes to autism via the gut-brain axis. Constipation may result in alteration of the gut microbiota. The clinical influence of constipation on ASD has not been fully researched. Thus, in this study we aimed to evaluate whether early childhood constipation influenced the risk of developing ASD using a nationwide population-based cohort study. Methods We identified 12,935 constipated children aged 3 years or younger from the National Health Insurance Research Database (NHIRD) in Taiwan from 1997 to 2013. Non-constipated children were also selected from the database and propensity score matching of age, gender, and underlying comorbidities was conducted with a ratio of 1:1. Kaplan-Meier analysis was applied to determine different levels of constipation severity and cumulative incidence of autism. Subgroup analysis was also applied in this study. Results The incidence rate of ASD was 12.36 per 100,000 person-months in the constipation group, which was higher than the rate of 7.84 per 100,000 person-months noted in the non-constipation controls. Constipated children had a significantly higher risk of autism when compared to the non-constipation group (crude relative risk = 1.458, 95% CI = 1.116-1.904; adjusted hazard ratio = 1.445, 95% CI = 1.095-1.907).Moreover, among constipated children, a higher number of laxative prescriptions, male gender, constipation during infancy, and atopic dermatitis were significantly associated with higher risks of ASD when compared to the non-constipation group. Conclusion Constipation in early childhood was correlated with a significantly increased risk of ASD. Clinicians should pay attention to the possibility of ASD in constipated children. Further research is necessary to study the possible pathophysiological mechanisms of this association.
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Affiliation(s)
- Yi-Feng Lee
- Division of Neonatology, Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Meng-Che Wu
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Gastroenterology, Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Kevin Sheng-Kai Ma
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- Department of Orthodontics and Dentofacial Orthopedics, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA, United States
| | - Jing-Yang Huang
- Center for Health Data Science, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Jing-Yang Hung,
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- *Correspondence: James Cheng-Chung Wei,
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Bosi G, Maynard BJ, Pironi F, Sayyaf Dezfuli B. Parasites and the neuroendocrine control of fish intestinal function: an ancient struggle between pathogens and host. Parasitology 2022; 149:1842-1861. [PMID: 36076315 PMCID: PMC11010486 DOI: 10.1017/s0031182022001160] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 08/03/2022] [Accepted: 08/11/2022] [Indexed: 12/29/2022]
Abstract
Most individual fish in wild and farmed populations can be infected with parasites. Fish intestines can harbour protozoans, myxozoans and helminths, which include several species of digeneans, cestodes, nematodes and acanthocephalans. Enteric parasites often induce inflammation of the intestine; the pathogen provokes changes in the host physiology, which will be genetically selected for if they benefit the parasite. The host response to intestinal parasites involves neural, endocrine and immune systems and interaction among these systems is coordinated by hormones, chemokines, cytokines and neurotransmitters including peptides. Intestinal fish parasites have effects on the components of the enteric nervous and endocrine systems; mechanical/chemical changes impair the activity of these systems, including gut motility and digestion. Investigations on the role of the neuroendocrine system in response to fish intestinal parasites are very few. This paper provides immunohistochemical and ultrastructural data on effects of parasites on the enteric nervous system and the enteric endocrine system in several fish–parasite systems. Emphasis is on the occurrence of 21 molecules including cholecystokinin-8, neuropeptide Y, enkephalins, galanin, vasoactive intestinal peptide and serotonin in infected tissues.
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Affiliation(s)
- Giampaolo Bosi
- Department of Veterinary Medicine and Animal Science, University of Milan, St. dell'Università 6, 26900 Lodi, Italy
| | - Barbara J. Maynard
- The Institute for Learning and Teaching, Colorado State University, Fort Collins, CO 80523, USA
| | - Flavio Pironi
- Department of Life Sciences and Biotechnology, University of Ferrara, St. Borsari 46, 44121 Ferrara, Italy
| | - Bahram Sayyaf Dezfuli
- Department of Life Sciences and Biotechnology, University of Ferrara, St. Borsari 46, 44121 Ferrara, Italy
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12
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Yasmin F, Sahito AM, Mir SL, Khatri G, Shaikh S, Gul A, Hassan SA, Koritala T, Surani S. Electrical neuromodulation therapy for inflammatory bowel disease. World J Gastrointest Pathophysiol 2022; 13:128-142. [PMID: 36187600 PMCID: PMC9516456 DOI: 10.4291/wjgp.v13.i5.128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 02/19/2022] [Accepted: 07/18/2022] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal (GI) tract. It has financial and quality of life impact on patients. Although there has been a significant advancement in treatments, a considerable number of patients do not respond to it or have severe side effects. Therapeutic approaches such as electrical neuromodulation are being investigated to provide alternate options. Although bioelectric neuromodulation technology has evolved significantly in the last decade, sacral nerve stimulation (SNS) for fecal incontinence remains the only neuromodulation protocol commonly utilized use for GI disease. For IBD treatment, several electrical neuromodulation techniques have been studied, such as vagus NS, SNS, and tibial NS. Several animal and clinical experiments were conducted to study the effectiveness, with encouraging results. The precise underlying mechanisms of action for electrical neuromodulation are unclear, but this modality appears to be promising. Randomized control trials are required to investigate the efficacy of intrinsic processes. In this review, we will discuss the electrical modulation therapy for the IBD and the data pertaining to it.
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Affiliation(s)
- Farah Yasmin
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Abdul Moiz Sahito
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Syeda Lamiya Mir
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Govinda Khatri
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Somina Shaikh
- Department of Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Ambresha Gul
- Department of Medicine, People’s University of Medical and Health Sciences, Nawabshah 67480, Pakistan
| | - Syed Adeel Hassan
- Department of Medicine, University of Louisville, Louiseville, KY 40292, United States
| | - Thoyaja Koritala
- Department of Medicine, Mayo Clinic, Rochester, NY 55902, United States
| | - Salim Surani
- Department of Medicine, Texas A&M University, College Station, TX 77843, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55902, United States
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13
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Wu Y, Cai Z, Liu L, Wang J, Li Y, Kang Y, An N. Impact of intravenous dexmedetomidine on gastrointestinal function recovery after laparoscopic hysteromyomectomy: a randomized clinical trial. Sci Rep 2022; 12:14640. [PMID: 36030343 PMCID: PMC9420113 DOI: 10.1038/s41598-022-18729-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 08/18/2022] [Indexed: 01/14/2023] Open
Abstract
Postoperative intestinal ileus is common after laparoscopic surgery, the incidence of those after hysterectomy was 9.2%. Anesthesia is one of the independent risk factors of postoperative ileus. Dexmedetomidine has been widely used in perioperative anesthesia and previous reports suggested that intraoperative dexmedetomidine may be associated with the improvement of gastrointestinal function recovery after abdominal surgery. We hypothesized that dexmedetomidine could improve gastrointestinal function recovery after laparoscopic hysteromyomectomy. Participants in elective laparoscopic hysteromyomectomy were enrolled with a single dose of 0.5 μg kg−1 dexmedetomidine or the same volume of placebo intravenously administered for 15 min, followed by continuous pumping of 0.2 μg kg−1 h−1 of corresponding drugs until 30 min before the end of surgery. The primary outcome was the time to first flatus. Secondary outcomes were the time to first oral feeding and the first defecation, the occurrence of flatulence, pain score and postoperative nausea and vomiting until 48 h after the surgery. Eventually, 106 participants (54 in dexmedetomidine group and 52 in placebo group) were included for final analysis. The time to first flatus (SD, 25.83 [4.18] vs 27.67 [3.77], P = 0.019), oral feeding time (SD, 27.29 [4.40] vs 28.92 [3.82], P = 0.044), the time to first defecation (SD, 59.82 [10.49] vs 63.89 [7.71], P = 0.025), abdominal distension (n%, 12 (22.2) vs 21 (40.4), P = 0.044), PONV at 24 h (n%, 10 (18.5) vs 19 (36.5), P = 0.037), NRS 6 h (3.15(0.68) vs 3.46 (0.87), P = 0.043) and NRS 12 h (3.43 (0.88) vs 3.85 (0.85), P = 0.014) of dexmedetomidine group were significantly shorter than those of the placebo group. Intraoperative dexmedetomidine reduced the time to first flatus, first oral feeding, and first defecation. These results suggested that this treatment may be a feasible strategy for improving postoperative gastrointestinal function recovery in patients undergoing laparoscopic hysteromyomectomy.
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Affiliation(s)
- Yu Wu
- Department of Anesthesiology, Bethune International Peace Hospital, Shijiazhuang, 050082, China.
| | - Zenghua Cai
- Department of Anesthesiology, Bethune International Peace Hospital, Shijiazhuang, 050082, China
| | - Lishuang Liu
- Department of Obstetrics and Gynecology, Bethune International Peace Hospital, Shijiazhuang, 050082, China
| | - Jinbao Wang
- Department of Anesthesiology, Bethune International Peace Hospital, Shijiazhuang, 050082, China
| | - Yanli Li
- Department of Anesthesiology, Bethune International Peace Hospital, Shijiazhuang, 050082, China
| | - Yuling Kang
- Department of Anesthesiology, Bethune International Peace Hospital, Shijiazhuang, 050082, China
| | - Ni An
- Department of Anesthesiology and Pain, Troop 32295 of the Chinese People's Liberation Army, Liaoyang, China
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14
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Lee HR, Sung JH. Multi-Organ-on-a-Chip for Realization of Gut-Skin Axis. Biotechnol Bioeng 2022; 119:2590-2601. [PMID: 35750599 DOI: 10.1002/bit.28164] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 05/24/2022] [Accepted: 06/21/2022] [Indexed: 11/06/2022]
Abstract
The concept of physiological link between the gut and the skin, known as the gut-skin axis, has been gaining more evidence recently. Although experimental data from animal and human studies support the existence of the gut-skin axis, in vitro model platforms that can test the hypothesis are lacking. Organ-on-a-chip offers the possibility of connecting different tissues and recapitulating interactions between them. In this study, we report a multi-organ chip that can capture the basic inter-organ communication between the gut and the skin. Its modular design enables separate culture and differentiation of the gut and skin tissues, and after assembly the two organs are connected via microfluidic channels than enables perfusion and mass transfer. We showed that the impairment of the gut barrier function exacerbated the adverse effect of fatty acids on skin cells, with decreased viability, increased level of cytokine secretion and human β-defensin-2 (hBD-2), an inflammatory dermal disease marker. Based on these results, we believe that our multi-organ chip can be a novel in vitro platform for recapitulating complex mechanisms underlying the gut-skin axis. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Hye Ri Lee
- Department of Chemical Engineering, Hongik University, Seoul, Korea
| | - Jong Hwan Sung
- Department of Chemical Engineering, Hongik University, Seoul, Korea
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15
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Wei L, Singh R, Ghoshal UC. Enterochromaffin Cells-Gut Microbiota Crosstalk: Underpinning the Symptoms, Pathogenesis, and Pharmacotherapy in Disorders of Gut-Brain Interaction. J Neurogastroenterol Motil 2022; 28:357-375. [PMID: 35719046 PMCID: PMC9274469 DOI: 10.5056/jnm22008] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/16/2022] [Accepted: 04/04/2022] [Indexed: 11/20/2022] Open
Abstract
Disorders of gut-brain interaction (DGBIs) are common conditions in community and clinical practice. As specialized enteroendocrine cells, enterochromaffin (EC) cells produce up to 95% of total body serotonin and coordinate luminal and basolateral communication in the gastrointestinal (GI) tract. EC cells affect a broad range of gut physiological processes, such as motility, absorption, secretion, chemo/mechanosensation, and pathologies, including visceral hypersensitivity, immune dysfunction, and impaired gastrointestinal barrier function. We aim to review EC cell and serotonin-mediated physiology and pathophysiology with particular emphasis on DGBIs. We explored the knowledge gap and attempted to suggest new perspectives of physiological and pathophysiological insights of DGBIs, such as (1) functional heterogeneity of regionally distributed EC cells throughout the entire GI tract; (2) potential pathophysiological mechanisms mediated by EC cell defect in DGBIs; (3) cellular and molecular mechanisms characterizing EC cells and gut microbiota bidirectional communication; (4) differential modulation of EC cells through GI segment-specific gut microbiota; (5) uncover whether crosstalk between EC cells and (i) luminal contents; (ii) enteric nervous system; and (iii) central nervous system are core mechanisms modulating gut-brain homeostasis; and (6) explore the therapeutic modalities for physiological and pathophysiological mechanisms mediated through EC cells. Insights discussed in this review will fuel the conception and realization of pathophysiological mechanisms and therapeutic clues to improve the management and clinical care of DGBIs.
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Affiliation(s)
- Lai Wei
- Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA
| | - Rajan Singh
- Department of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, NV, USA
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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16
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Van Remoortel S, Lambeets L, Timmermans JP. Neuro-immune interactions and the role of Mas-related G protein-coupled receptors in the gastrointestinal tract. Anat Rec (Hoboken) 2022; 306:1131-1139. [PMID: 35694864 DOI: 10.1002/ar.25008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 05/11/2022] [Accepted: 05/20/2022] [Indexed: 11/10/2022]
Abstract
Over the past decade, the research field dealing with the role of a new family of Rhodopsin A-like G protein-coupled receptors, that is, the family of Mas-related G protein-coupled receptors (Mrgprs) has expanded enormously. A plethora of recent studies have provided evidence that Mrgprs are key players in itch and pain, as well as in the initiation and modulation of inflammatory/allergic responses in the skin. Over the years, it has become clear that this role is not limited to the skin, but extends to other mucosal surfaces such as the respiratory tract and the gastrointestinal (GI) tract. In the GI tract, Mrgprs have emerged as novel interoceptive sensory pathways linked to health and disease, and are in close functional association with the gut's immune system. This review aims to provide an update of our current knowledge on the expression, distribution and function of members of this Mrgpr family in intrinsic and extrinsic neuro-immune pathways related to the GI system.
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Affiliation(s)
- Samuel Van Remoortel
- Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium
| | - Lana Lambeets
- Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium
| | - Jean-Pierre Timmermans
- Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium
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17
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Kadowaki M, Yamamoto T, Hayashi S. Neuro-immune crosstalk and food allergy: Focus on enteric neurons and mucosal mast cells. Allergol Int 2022; 71:278-287. [PMID: 35410807 DOI: 10.1016/j.alit.2022.03.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Indexed: 12/12/2022] Open
Abstract
The nervous system and the immune system individually play important roles in regulating the processes necessary to maintain physiological homeostasis, respond to acute stress and protect against external threats. These two regulating systems for maintaining the living body had often been assumed to function independently. Allergies develop as a result of an overreaction of the immune system to substances that are relatively harmless to the body, such as food, pollen and dust mites. Therefore, it has been generally supposed that the development and pathogenesis of allergies can be explained through an immunological interpretation. Recently, however, neuro-immune crosstalk has attracted increasing attention. Consequently, it is becoming clear that there is close morphological proximity and physiological and pathophysiological interactions between neurons and immune cells in various peripheral tissues. Thus, researchers are now beginning to appreciate that neuro-immune interactions may play a role in tissue homeostasis and the pathophysiology of immune-mediated disease, but very little information is available on the molecular basis of these interactions. Mast cells are a part of the innate immune system implicated in allergic reactions and the regulation of host-pathogen interactions. Mast cells are ubiquitous in the body, and these cells are often found in close proximity to nerve fibers in various tissues, including the lamina propria of the intestine. Mast cells and neurons are thought to communicate bidirectionally to modulate neurophysiological effects and mast cell functions, which suggests that neuro-immune interactions may be involved in the pathology of allergic diseases.
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18
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Buscail E, Deraison C. Postoperative Ileus: a Pharmacological Perspective. Br J Pharmacol 2022; 179:3283-3305. [PMID: 35048360 DOI: 10.1111/bph.15800] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 12/31/2021] [Accepted: 01/05/2022] [Indexed: 11/29/2022] Open
Abstract
Post-operative ileus (POI) is a frequent complication after abdominal surgery. The consequences of POI can be potentially serious such as bronchial inhalation or acute functional renal failure. Numerous advances in peri-operative management, particularly early rehabilitation, have made it possible to decrease POI. Despite this, the rate of prolonged POI ileus remains high and can be as high as 25% of patients in colorectal surgery. From a pathophysiological point of view, POI has two phases, an early neurological phase and a later inflammatory phase, to which we could add a "pharmacological" phase during which analgesic drugs, particularly opiates, play a central role. The aim of this review article is to describe the phases of the pathophysiology of POI, to analyse the pharmacological treatments currently available through published clinical trials and finally to discuss the different research areas for potential pharmacological targets.
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Affiliation(s)
- Etienne Buscail
- IRSD, INSERM, INRAE, ENVT, University of Toulouse, CHU Purpan (University Hospital Centre), Toulouse, France.,Department of digestive surgery, colorectal surgery unit, Toulouse University Hospital, Toulouse, France
| | - Céline Deraison
- IRSD, INSERM, INRAE, ENVT, University of Toulouse, CHU Purpan (University Hospital Centre), Toulouse, France
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19
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Koda S, Zhu XQ, Zheng KY, Yan C. Molecular Mechanisms of Clonorchis sinensis-Host Interactions and Implications for Vaccine Development. Front Cell Dev Biol 2022; 9:781768. [PMID: 35118069 PMCID: PMC8804234 DOI: 10.3389/fcell.2021.781768] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 12/14/2021] [Indexed: 12/12/2022] Open
Abstract
Infections caused by Clonorchis sinensis remain a significant public health challenge for both humans and animals, causing pyogenic cholangitis, cholelithiasis, cholecystitis, biliary fibrosis, and even cholangiocarcinoma. However, the strategies used by the parasite and the immunological mechanisms used by the host have not yet been fully understood. With the advances in technologies and the accumulated knowledge of host-parasite interactions, many vaccine candidates against liver flukes have been investigated using different strategies. In this review, we explore and analyze in-depth the immunological mechanisms involved in the pathogenicity of C. sinensis. We highlight the different mechanisms by which the parasite interacts with its host to induce immune responses. All together, these data will allow us to have a better understanding of molecular mechansism of host-parasite interactions, which may shed lights on the development of an effective vaccine against C. sinensis.
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Affiliation(s)
- Stephane Koda
- Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, China
| | - Xing-Quan Zhu
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, China
| | - Kui-Yang Zheng
- Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, China
- *Correspondence: Kui-Yang Zheng, ; Chao Yan,
| | - Chao Yan
- Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, National Experimental Demonstration Center for Basic Medicine Education, Xuzhou Medical University, Xuzhou, China
- *Correspondence: Kui-Yang Zheng, ; Chao Yan,
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20
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Yip JL, Balasuriya GK, Spencer SJ, Hill-Yardin EL. The Role of Intestinal Macrophages in Gastrointestinal Homeostasis: Heterogeneity and Implications in Disease. Cell Mol Gastroenterol Hepatol 2021; 12:1701-1718. [PMID: 34506953 PMCID: PMC8551786 DOI: 10.1016/j.jcmgh.2021.08.021] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 12/13/2022]
Abstract
Intestinal macrophages play a key role in the gut immune system and the regulation of gastrointestinal physiology, including gut motility and secretion. Their ability to keep the gut from chronic inflammation despite constantly facing foreign antigens has been an important focus in gastrointestinal research. However, the heterogeneity of intestinal macrophages has impeded our understanding of their specific roles. It is now becoming clear that subsets of intestinal macrophages play diverse roles in various gastrointestinal diseases. This occurs through a complex interplay between cytokine production and enteric nervous system activation that differs for each pathologic condition. Key diseases and disorders in which intestinal macrophages play a role include postoperative ileus, inflammatory bowel disease, necrotizing enterocolitis, as well as gastrointestinal disorders associated with human immunodeficiency virus and Parkinson's disease. Here, we review the identification of intestinal macrophage subsets based on their origins and functions, how specific subsets regulate gut physiology, and the potential for these heterogeneous subpopulations to contribute to disease states. Furthermore, we outline the potential for these subpopulations to provide unique targets for the development of novel therapies for these disorders.
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Affiliation(s)
| | | | - Sarah J. Spencer
- School of Health and Biomedical Sciences,Australian Research Council Centre of Excellence for Nanoscale Biophotonics, Royal Melbourne Instutite of Technology, Melbourne, Victoria, Australia
| | - Elisa L. Hill-Yardin
- School of Health and Biomedical Sciences,Correspondence Address correspondence to: Elisa L. Hill-Yardin, PhD, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia.
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21
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De la Fuente M. The Role of the Microbiota-Gut-Brain Axis in the Health and Illness Condition: A Focus on Alzheimer's Disease. J Alzheimers Dis 2021; 81:1345-1360. [PMID: 33935086 DOI: 10.3233/jad-201587] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Trillions of commensal microbes live in our body, the majority in the gut. This gut microbiota is in constant interaction with the homeostatic systems, the nervous, immune and endocrine systems, being fundamental for their appropriate development and function as well as for the neuroimmunoendocrine communication. The health state of an individual is understood in the frame of this communication, in which the microbiota-gut-brain axis is a relevant example. This bidirectional axis is constituted in early age and is affected by many environmental and lifestyle factors such as diet and stress, among others, being involved in the adequate maintenance of homeostasis and consequently in the health of each subject and in his/her rate of aging. For this, an alteration of gut microbiota, as occurs in a dysbiosis, and the associated gut barrier deterioration and the inflammatory state, affecting the function of immune, endocrine and nervous systems, in gut and in all the locations, is in the base of a great number of pathologies as those that involve alterations in the brain functions. There is an age-related deterioration of microbiota and the homeostatic systems due to oxi-inflamm-aging, and thus the risk of aging associated pathologies such as the neurodegenerative illness. Currently, this microbiota-gut-brain axis has been considered to have a relevant role in the pathogenesis of Alzheimer's disease and represents an important target in the prevention and slowdown of the development of this pathology. In this context, the use of probiotics seems to be a promising help.
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Affiliation(s)
- Mónica De la Fuente
- Department of Genetics, Physiology and Microbiology (Animal Physiology Unit), School of Biology, Complutense University of Madrid. Institute of Investigation of Hospital 12 de Octubre (i+12), Madrid, Spain
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22
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Chu X, Zhang B, Koeken VACM, Gupta MK, Li Y. Multi-Omics Approaches in Immunological Research. Front Immunol 2021; 12:668045. [PMID: 34177908 PMCID: PMC8226116 DOI: 10.3389/fimmu.2021.668045] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/28/2021] [Indexed: 12/14/2022] Open
Abstract
The immune system plays a vital role in health and disease, and is regulated through a complex interactive network of many different immune cells and mediators. To understand the complexity of the immune system, we propose to apply a multi-omics approach in immunological research. This review provides a complete overview of available methodological approaches for the different omics data layers relevant for immunological research, including genetics, epigenetics, transcriptomics, proteomics, metabolomics, and cellomics. Thereafter, we describe the various methods for data analysis as well as how to integrate different layers of omics data. Finally, we discuss the possible applications of multi-omics studies and opportunities they provide for understanding the complex regulatory networks as well as immune variation in various immune-related diseases.
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Affiliation(s)
- Xiaojing Chu
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
| | - Bowen Zhang
- Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
| | - Valerie A. C. M. Koeken
- Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Manoj Kumar Gupta
- Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
| | - Yang Li
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
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23
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Stakenborg N, Boeckxstaens GE. Bioelectronics in the brain-gut axis: focus on inflammatory bowel disease (IBD). Int Immunol 2021; 33:337-348. [PMID: 33788920 PMCID: PMC8183669 DOI: 10.1093/intimm/dxab014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 03/30/2021] [Indexed: 12/17/2022] Open
Abstract
Accumulating evidence shows that intestinal homeostasis is mediated by cross-talk between the nervous system, enteric neurons and immune cells, together forming specialized neuroimmune units at distinct anatomical locations within the gut. In this review, we will particularly discuss how the intrinsic and extrinsic neuronal circuitry regulates macrophage function and phenotype in the gut during homeostasis and aberrant inflammation, such as observed in inflammatory bowel disease (IBD). Furthermore, we will provide an overview of basic and translational IBD research using these neuronal circuits as a novel therapeutic tool. Finally, we will highlight the different challenges ahead to make bioelectronic neuromodulation a standard treatment for intestinal immune-mediated diseases.
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Affiliation(s)
- Nathalie Stakenborg
- Center of Intestinal Neuro-immune Interaction, Translational Research Center for GI Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, University of Leuven, Herestraat 49, O&N1 bus 701, Leuven 3000, Belgium
| | - Guy E Boeckxstaens
- Center of Intestinal Neuro-immune Interaction, Translational Research Center for GI Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, University of Leuven, Herestraat 49, O&N1 bus 701, Leuven 3000, Belgium
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24
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Survival of metazoan parasites in fish: Putting into context the protective immune responses of teleost fish. ADVANCES IN PARASITOLOGY 2021; 112:77-132. [PMID: 34024360 DOI: 10.1016/bs.apar.2021.03.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Defence mechanisms of fish can be divided into specific and non-specific that act in concert and are often interdependent. Most fish in both wild and cultured populations are vulnerable to metazoan parasites. Endoparasitic helminths include several species of digeneans, cestodes, nematodes, and acanthocephalans. Although they may occur in large numbers, helminth infections rarely result in fish mortality. Conversely, some ectoparasites cause mass mortality in farmed fish. Given the importance of fish innate immunity, this review addresses non-specific defence mechanisms of fish against metazoan parasites, with emphasis on granulocyte responses involving mast cells, neutrophils, macrophages, rodlet cells, and mucous cells. Metazoan parasites are important disease agents that affect wild and farmed fish and can induce high economic loss and, as pathogen organisms, deserve considerable attention. The paper will provide our light and transmission electron microscopy data on metazoan parasites-fish innate immune and neuroendocrine systems. Insights about the structure and functions of the cell types listed above and a brief account of the effects and harms of each metazoan taxon to specific fish apparati/organs will be presented.
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25
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Guards! Guards! How innate lymphoid cells ensure local law and order. Biomed J 2021; 44:105-111. [PMID: 33994144 PMCID: PMC8178564 DOI: 10.1016/j.bj.2021.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 04/19/2021] [Indexed: 11/20/2022] Open
Abstract
This special issue of the Biomedical Journal is dedicated to the latest official recruits in the field of immunology: innate lymphoid cells, the tissue-resident sentinels and first responders to damage or invasion. Subsequently, we consider extracellular vesicle release during bacterial infection, how immunomodulation can avoid compromising Mycobacterium tuberculosis clearance, and how innate immunity jeopardises the organism during rheumatoid arthritis. Moreover, we ponder over the predictive value of cardiac troponin in influenza, the virtues of cashew nuts and bilirubin, as well as holes in the heart. Finally, we learn that mandibular movement during swallowing increases with the vertical dimension of occlusion, and that early controlled relaxation incisions restore the blood supply to the extremities in harlequin ichthyosis neonates.
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26
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Kneusels J, Kaehler M, Cascorbi I, Wedel T, Neunlist M, Lucius R, Cossais F. Limited Impact of 6-Mercaptopurine on Inflammation-Induced Chemokines Expression Profile in Primary Cultures of Enteric Nervous System. Neurochem Res 2021; 46:1781-1793. [PMID: 33864170 PMCID: PMC8187225 DOI: 10.1007/s11064-021-03324-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 04/04/2021] [Accepted: 04/09/2021] [Indexed: 01/09/2023]
Abstract
Increasing evidences indicate that the enteric nervous system (ENS) and enteric glial cells (EGC) play important regulatory roles in intestinal inflammation. Mercaptopurine (6-MP) is a cytostatic compound clinically used for the treatment of inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease. However, potential impacts of 6-MP on ENS response to inflammation have not been evaluated yet. In this study, we aimed to gain deeper insights into the profile of inflammatory mediators expressed by the ENS and on the potential anti-inflammatory impact of 6-MP in this context. Genome-wide expression analyses were performed on ENS primary cultures exposed to lipopolysaccharide (LPS) and 6-MP alone or in combination. Differential expression of main hits was validated by quantitative real-time PCR (qPCR) using a cell line for EGC. ENS cells expressed a broad spectrum of cytokines and chemokines of the C-X-C motif ligand (CXCL) family under inflammatory stress. Induction of Cxcl5 and Cxcl10 by inflammatory stimuli was confirmed in EGC. Inflammation-induced protein secretion of TNF-α and Cxcl5 was partly inhibited by 6-MP in ENS primary cultures but not in EGC. Further work is required to identify the cellular mechanisms involved in this regulation. These findings extend our knowledge of the anti-inflammatory properties of 6-MP related to the ENS and in particular of the EGC-response to inflammatory stimuli.
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Affiliation(s)
- Jan Kneusels
- Institute of Anatomy, Kiel University, Kiel, Germany.
| | - Meike Kaehler
- Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany
| | - Ingolf Cascorbi
- Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany
| | - Thilo Wedel
- Institute of Anatomy, Kiel University, Kiel, Germany
| | | | - Ralph Lucius
- Institute of Anatomy, Kiel University, Kiel, Germany
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27
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Douglas B, Oyesola O, Cooper MM, Posey A, Tait Wojno E, Giacomin PR, Herbert DR. Immune System Investigation Using Parasitic Helminths. Annu Rev Immunol 2021; 39:639-665. [PMID: 33646858 DOI: 10.1146/annurev-immunol-093019-122827] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Coevolutionary adaptation between humans and helminths has developed a finely tuned balance between host immunity and chronic parasitism due to immunoregulation. Given that these reciprocal forces drive selection, experimental models of helminth infection are ideally suited for discovering how host protective immune responses adapt to the unique tissue niches inhabited by these large metazoan parasites. This review highlights the key discoveries in the immunology of helminth infection made over the last decade, from innate lymphoid cells to the emerging importance of neuroimmune connections. A particular emphasis is placed on the emerging areas within helminth immunology where the most growth is possible, including the advent of genetic manipulation of parasites to study immunology and the use of engineered T cells for therapeutic options. Lastly,we cover the status of human challenge trials with helminths as treatment for autoimmune disease, which taken together, stand to keep the study of parasitic worms at the forefront of immunology for years to come.
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Affiliation(s)
- Bonnie Douglas
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; ,
| | - Oyebola Oyesola
- Department of Immunology, University of Washington, Seattle, Washington 98109, USA; ,
| | - Martha M Cooper
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia; ,
| | - Avery Posey
- Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; .,Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.,Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania 19104, USA
| | - Elia Tait Wojno
- Department of Immunology, University of Washington, Seattle, Washington 98109, USA; ,
| | - Paul R Giacomin
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia; ,
| | - De'Broski R Herbert
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; ,
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Dou D, Liang J, Zhai X, Li G, Wang H, Han L, Lin L, Ren Y, Liu S, Liu C, Guo W, Li J. Oxytocin signalling in dendritic cells regulates immune tolerance in the intestine and alleviates DSS-induced colitis. Clin Sci (Lond) 2021; 135:597-611. [PMID: 33564880 DOI: 10.1042/cs20201438] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 02/05/2021] [Accepted: 02/09/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that is associated with immune dysfunction. Recent studies have indicated that the neurosecretory hormone oxytocin (OXT) has been proven to alleviate experimental colitis. METHODS We investigated the role of OXT/OXT receptor (OXTR) signalling in dendritic cells (DCs) using mice with specific OXTR deletion in CD11c+ cells (OXTRflox/flox×CD11c-cre mice) and a dextran sulfate sodium (DSS)-induced colitis model. RESULTS The level of OXT was abnormal in the serum or colon tissue of DSS-induced colitis mice or the plasma of UC patients. Both bone marrow-derived DCs (BMDCs) and lamina propria DCs (LPDCs) express OXTR. Knocking out OXTR in DCs exacerbated DSS-induced acute and chronic colitis in mice. In contrast, the injection of OXT-pretreated DCs significantly ameliorated colitis. Mechanistically, OXT prevented DC maturation through the phosphatidylinositol 4,5-bisphosphate 3-kinase (Pi3K)/AKT pathway and promoted phagocytosis, adhesion and cytokine modulation in DCs. Furthermore, OXT pre-treated DCs prevent CD4+ T cells differentiation to T helper 1 (Th1) and Th17. CONCLUSIONS Our results suggest that OXT-induced tolerogenic DCs efficiently protect against experimental colitis via Pi3K/AKT pathway. Our work provides evidence that the nervous system participates in the immune regulation of colitis by modulating DCs. Our findings suggest that generating ex vivo DCs pretreated with OXT opens new therapeutic perspectives for the treatment of UC in humans.
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Affiliation(s)
- Dandan Dou
- Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Jinghui Liang
- Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Xiangyu Zhai
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Guosheng Li
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Hongjuan Wang
- Department of Gastroenterology, Second Hospital, Shandong University, Jinan 250000, China
| | - Liying Han
- College of Life Science, Shandong Normal University, Jinan 250014, China
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266000, China
| | - Lin Lin
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Yifei Ren
- Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Shilian Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Chuanyong Liu
- Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Wei Guo
- Department of Colorectal Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Jingxin Li
- Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
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29
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Bhuiyan P, Wang YW, Sha HH, Dong HQ, Qian YN. Neuroimmune connections between corticotropin-releasing hormone and mast cells: novel strategies for the treatment of neurodegenerative diseases. Neural Regen Res 2021; 16:2184-2197. [PMID: 33818491 PMCID: PMC8354134 DOI: 10.4103/1673-5374.310608] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis, which plays a major role in the body’s immune response to stress. Mast cells are both sensors and effectors in the interaction between the nervous and immune systems. As first responders to stress, mast cells can initiate, amplify and prolong neuroimmune responses upon activation. Corticotropin-releasing hormone plays a pivotal role in triggering stress responses and related diseases by acting on its receptors in mast cells. Corticotropin-releasing hormone can stimulate mast cell activation, influence the activation of immune cells by peripheral nerves and modulate neuroimmune interactions. The latest evidence shows that the release of corticotropin-releasing hormone induces the degranulation of mast cells under stress conditions, leading to disruption of the blood-brain barrier, which plays an important role in neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, autism spectrum disorder and amyotrophic lateral sclerosis. Recent studies suggest that stress increases intestinal permeability and disrupts the blood-brain barrier through corticotropin-releasing hormone-mediated activation of mast cells, providing new insight into the complex interplay between the brain and gastrointestinal tract. The neuroimmune target of mast cells is the site at which the corticotropin-releasing hormone directly participates in the inflammatory responses of nerve terminals. In this review, we focus on the neuroimmune connections between corticotropin-releasing hormone and mast cells, with the aim of providing novel potential therapeutic targets for inflammatory, autoimmune and nervous system diseases.
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Affiliation(s)
- Piplu Bhuiyan
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yi-Wei Wang
- Department of Anesthesiology, Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu Province, China
| | - Huan-Huan Sha
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Hong-Quan Dong
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yan-Ning Qian
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
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30
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The intestinal neuro-immune axis: crosstalk between neurons, immune cells, and microbes. Mucosal Immunol 2021; 14:555-565. [PMID: 33542493 PMCID: PMC8075967 DOI: 10.1038/s41385-020-00368-1] [Citation(s) in RCA: 148] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 11/16/2020] [Accepted: 11/21/2020] [Indexed: 02/04/2023]
Abstract
The gastrointestinal tract is densely innervated by a complex network of neurons that coordinate critical physiological functions. Here, we summarize recent studies investigating the crosstalk between gut-innervating neurons, resident immune cells, and epithelial cells at homeostasis and during infection, food allergy, and inflammatory bowel disease. We introduce the neuroanatomy of the gastrointestinal tract, detailing gut-extrinsic neuron populations from the spinal cord and brain stem, and neurons of the intrinsic enteric nervous system. We highlight the roles these neurons play in regulating the functions of innate immune cells, adaptive immune cells, and intestinal epithelial cells. We discuss the consequences of such signaling for mucosal immunity. Finally, we discuss how the intestinal microbiota is integrated into the neuro-immune axis by tuning neuronal and immune interactions. Understanding the molecular events governing the intestinal neuro-immune signaling axes will enhance our knowledge of physiology and may provide novel therapeutic targets to treat inflammatory diseases.
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31
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Receptors for pro-resolving mediators as a therapeutic tool for smooth muscle remodeling-associated disorders. Pharmacol Res 2020; 164:105340. [PMID: 33276103 DOI: 10.1016/j.phrs.2020.105340] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/25/2020] [Accepted: 11/26/2020] [Indexed: 12/16/2022]
Abstract
Respiratory airway, blood vessel and intestinal wall remodeling, in which smooth muscle remodeling plays a major role, is a key pathological event underlying the development of several associated diseases, including asthma, cardiovascular disorders (e.g., atherosclerosis, hypertension, and aneurism formation), and inflammatory bowel disease. However, the mechanisms underlying these remodeling processes remain poorly understood. We hypothesize that the creation of chronic inflammation-mediated networks that support and exacerbate the airway, as well as vascular and intestinal wall remodeling, is a crucial pathogenic mechanism governing the development of the associated diseases. The failed inflammation resolution might be one of the causal pathogenic mechanisms. Hence, it is reasonable to assume that applying specialized, pro-resolving mediators (SPMs), acting via cognate G-protein coupled receptors (GPCRs), could potentially be an effective pathway for treating these disorders. However, several obstacles, such as poor understanding of the SPM/receptor signaling pathways, SMP rapid inactivation as well as their complex and costly synthesis, limit their translational potential. In this connection, stable, small-molecule SPM mimetics and receptor agonists have emerged as new, potentially suitable drugs. It has been recently shown in preclinical studies that they can effectively attenuate the manifestations of asthma, atherosclerosis and Crohn's disease. Remarkably, some biased SPM receptor agonists, which cause a signaling response in the desired inflammation pro-resolving direction, revealed similar beneficial effects. These encouraging observations suggest that SPM mimetics and receptor agonists can be applied as a novel approach for the treatment of various chronic inflammation conditions, including airway, vascular and intestinal wall remodeling-associated disorders.
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32
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Abstract
The gut-brain axis is a coordinated communication system that not only maintains homeostasis, but significantly influences higher cognitive functions and emotions, as well as neurological and behavioral disorders. Among the large populations of sensory and motor neurons that innervate the gut, insights into the function of primary afferent nociceptors, whose cell bodies reside in the dorsal root ganglia and nodose ganglia, have revealed their multiple crosstalk with several cell types within the gut wall, including epithelial, vascular, and immune cells. These bidirectional communications have immunoregulatory functions, control host response to pathogens, and modulate sensations associated with gastrointestinal disorders, through activation of immune cells and glia in the peripheral and central nervous system, respectively. Here, we will review the cellular and neurochemical basis of these interactions at the periphery, in dorsal root ganglia, and in the spinal cord. We will discuss the research gaps that should be addressed to get a better understanding of the multifunctional role of sensory neurons in maintaining gut homeostasis and regulating visceral sensitivity.
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Affiliation(s)
- Nasser Abdullah
- Department of Physiology and Pharmacology, Inflammation Research Network-Snyder Institute for Chronic Diseases and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Manon Defaye
- Department of Physiology and Pharmacology, Inflammation Research Network-Snyder Institute for Chronic Diseases and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Christophe Altier
- Department of Physiology and Pharmacology, Inflammation Research Network-Snyder Institute for Chronic Diseases and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
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33
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Cappelletti M, Tognon E, Vona L, Basello K, Costanzi A, Speciani MC, Speciani AF. Food-specific serum IgG and symptom reduction with a personalized, unrestricted-calorie diet of six weeks in Irritable Bowel Syndrome (IBS). Nutr Metab (Lond) 2020; 17:101. [PMID: 33292297 PMCID: PMC7708901 DOI: 10.1186/s12986-020-00528-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 11/24/2020] [Indexed: 12/13/2022] Open
Abstract
Background Irritable Bowel Syndrome (IBS) is a widespread disease with variable symptoms that have an important impact on the quality of life. Despite the prevalence of IBS, its etiology and pathophysiology are still to be fully understood, but immune response is known to be involved. In this study, we investigated the variation of two specific cytokines, B-cell activating factor (BAFF) and platelet-activating factor (PAF), the levels of food-specific IgG and the symptom severity, using Irritable Bowel Syndrome—Symptom Severity Score (IBS-SSS), following a personalized and unrestricted-calorie diet.
Methods We enrolled 30 subjects with diagnosis of IBS, according to Rome-IV criteria, whose inflammatory markers were measured at baseline and after 6 weeks of dietary intervention. The subjects were monitored in a general practice outpatient setting and nutritional advice was offered remotely via two telephone sessions with a nutritionist.
Results BAFF and PAF values did not differ between baseline and end of study, both in compliant (C) and non-compliant (NC) subjects. IgG levels significantly decreased only in compliant subjects: 37.32 (23.24–93.67) IU/mL; 27.9 (7.56–93.96) IU/mL (p = 0.02) and in non-compliant went from 51.83 (13.17–113.1) IU/mL to 44.06 (4.96–255.4) IU/mL (p = 0.97, ns). IBS-SSS significantly decreased in both compliant subjects, from 245 (110–480) to 110 (0–140) (p < 0.0001), and non compliant subjects, from 250 (155–370) to 100 (7–220) (p < 0.0001). Comparing IBS-SSS between week 3 and week 6, only compliant subjects had a significant reduction, from 155 (50–355) to 110 (0–140) (p = 0.005), versus non-compliant, from 115 (35–315) to 100 (7–220) (p = 0.33, ns). Conclusion These findings support the rapid efficacy and suitability of a personalized dietetic intervention with outside consultation in IBS. Trial registration: ClinicalTrials.gov ID NCT04348760 Registered April 15, 2020 (retrospectively registered) https://clinicaltrials.gov/show/NCT04348760
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Affiliation(s)
- Mattia Cappelletti
- Inflammation Society, 18 Woodlands Park, Bexley, DA52EL, UK. .,SMA Servizi Medici Associati, Via F. Vegezio, 12, 20149, Milan, Italy.
| | - Emiliana Tognon
- Inflammation Society, 18 Woodlands Park, Bexley, DA52EL, UK.,SMA Servizi Medici Associati, Via F. Vegezio, 12, 20149, Milan, Italy
| | - Linda Vona
- Inflammation Society, 18 Woodlands Park, Bexley, DA52EL, UK.,SMA Servizi Medici Associati, Via F. Vegezio, 12, 20149, Milan, Italy
| | - Katia Basello
- GEK Lab - Cryolab University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy
| | - Andrea Costanzi
- GEK Lab - Cryolab University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy
| | - Michela Carola Speciani
- Inflammation Society, 18 Woodlands Park, Bexley, DA52EL, UK.,SMA Servizi Medici Associati, Via F. Vegezio, 12, 20149, Milan, Italy
| | - Attilio Francesco Speciani
- Inflammation Society, 18 Woodlands Park, Bexley, DA52EL, UK.,SMA Servizi Medici Associati, Via F. Vegezio, 12, 20149, Milan, Italy.,GEK Lab - Cryolab University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy
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