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Xiao Z, Xie J, Zhao X, Chen X, Lu Y, Xu Y, Wu M, An L, Li Q. Role of Pyroptosis in inflammatory bowel disease. Int Immunopharmacol 2025; 155:114619. [PMID: 40209313 DOI: 10.1016/j.intimp.2025.114619] [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] [Received: 01/30/2025] [Revised: 03/21/2025] [Accepted: 04/03/2025] [Indexed: 04/12/2025]
Abstract
Inflammatory bowel disease (IBD) is a serious chronic condition marked by persistent and recurrent intestinal ulcers. Although the exact cause of IBD remains unclear, it is generally accepted that a complex interaction among dietary factors, gut microbiota, and immune responses in genetically predisposed individuals contributes to its development. Pyroptosis, an inflammatory form of programmed cell death activated by inflammasomes, is marked by the rupture of cell membranes and the subsequent release of inflammatory mediators. Emerging evidence indicates that pyroptosis plays a crucial role in the pathogenesis of IBD. Moderate pyroptosis activation can enhance intestinal immune defenses, while excessive inflammasome activation can trigger an inflammatory cascade, resulting in increased damage to intestinal tissues. This article reviews the molecular mechanisms underlying pyroptosis and highlights its role in the onset and progression of IBD. Furthermore, We explore recent advancements in IBD treatment, focusing on small molecule compounds that specifically target and inhibit pyroptosis.
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Affiliation(s)
- Zhiyi Xiao
- The Clinical Medical College, Guizhou Medical University, Guiyang 550004, China
| | - Jiling Xie
- The Clinical Medical College, Guizhou Medical University, Guiyang 550004, China
| | - Xun Zhao
- Department of Gastroenterology, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China
| | - Xiangjun Chen
- The Clinical Medical College, Guizhou Medical University, Guiyang 550004, China
| | - Yihong Lu
- The Clinical Medical College, Guizhou Medical University, Guiyang 550004, China
| | - Yuanzhao Xu
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China
| | - Manqing Wu
- Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China
| | - Lingyue An
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China.
| | - Qing Li
- Department of Gastroenterology and Surgery, Guizhou Provincial People's Hospital, Guiyang, 550002, Guizhou, China.
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Liu XJ, Ye-er-tai YLY, Jia YB, Wu CH, Wang XX, Yang KM, Yao X, Ling JH. Runchangningshen paste activates NLRP6 inflammasome-mediated autophagy to stimulate colonic mucin-2 secretion and modulates mucosal microbiota in functional constipation. World J Gastroenterol 2025; 31:102256. [PMID: 40061589 PMCID: PMC11886036 DOI: 10.3748/wjg.v31.i9.102256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 12/06/2024] [Accepted: 01/02/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Runchangningshen paste (RCNSP) is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey. It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation. The pathophysiology of functional constipation (FC) is associated with a reduction in mucin-2 (MUC2) secretion and microbial dysbiosis. AIM To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota. METHODS Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action. FC model was induced via loperamide gavage (16 mg/kg) twice daily for 7 days. Applying defecation function and gastrointestinal motility to assess constipation severity. Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology. Transmission electron microscope was used to observe the ultrastructure of goblet cells (GCs). Immunofluorescence colocalization, quantitative PCR, and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway. 16S rDNA was employed to sequence the gut mucosal microbiota. RESULTS RCNSP contained 12 components with potential laxative effects. It enhanced defecation function, accelerated gastrointestinal motility, and maintained colonic mucosal integrity. RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure. At the molecular level, RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway. Through 16S rDNA sequencing analysis, RCNSP significantly altered the mucosal microbiota composition. Specifically, it increased beneficial bacterial strains while reducing harmful ones. Simultaneously, RCNSP reduced butyrate-producing bacteria like Proteobacteria, Enterobacteriaceae, Blautia, and Eubacterium and decreased hydrogen sulfide-producing species, such as Prevotellaceae. It also reduced bile acid-inhibiting species, such as g_Eubacter_coprostanoligenes_group and Erysipelotrichaceae while increasing bile acid-producing species, such as Colidextribacter. CONCLUSION Our findings suggested that RCNSP ameliorated constipation through a dual mechanism: It stimulated colonic MUC2 secretion by activating NLRP6 inflammasome-mediated autophagy and modulated the composition of the mucosal microbiota.
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Affiliation(s)
- Xue-Jiao Liu
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Ye-li-ya Ye-er-tai
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Yue-Bo Jia
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Chen-Heng Wu
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Xiang-Xiang Wang
- School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ke-Ming Yang
- Department of Gastroenterology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, Guangdong Province, China
| | - Xuan Yao
- Guangdong Shaxi Pharmaceutical Co., Ltd, Zhongshan 528471, Guangdong Province, China
| | - Jiang-Hong Ling
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
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Zhang X, Wang S, Xie J, Wang J, Gu Y, Wu B, Zhang Y, Yan T, Jia Y. Multi-platform analysis revealed the substance basis and mechanism of Wei-Tong-Xin in ameliorating ENS dysfunction for dyspepsia treatment. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118875. [PMID: 39362321 DOI: 10.1016/j.jep.2024.118875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/19/2024] [Accepted: 09/30/2024] [Indexed: 10/05/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Duodenal motility disorder is a contributing factor to dyspepsia. The traditional Chinese medicine (TCM) formula Wei-Tong-Xin (WTX), originated from the famous ancient Chinese formula "Wan Ying Yuan", has been demonstrated efficacy in alleviating dyspepsia. AIM OF THE STUDY The current study aims to elucidate the chemical composition of WTX to establish the pharmacodynamic material basis. On the basis of component, in depth to illuminate the mechanism by which WTX treats dyspepsia via constructing the comprehensive analysis of multi-platform. MATERIALS AND METHODS The chemical constituents of WTX were systematically analyzed by UHPLC-Q-TOF-MS/MS data processing methods. Based on this, network pharmacology was employed to predict the mechanism by which WTX improved dyspepsia. The dyspepsia mouse model was constructed, and histopathology as well as intestinal permeability were assessed using H&E staining, PAS staining and FITC-dextran assay. Protein expression was detected using Western blot, immunofluorescence, immunohistochemistry and ELISA kits. RESULTS A total of 100 chemical components of WTX were preliminarily identified. Network pharmacological analysis indicated that the therapeutic mechanism of WTX in treating dyspepsia may be related to the regulation of inflammation and oxidative stress-related signaling pathways. In vivo studies showed that WTX mitigated duodenal inflammation and oxidative stress responses, repairing the intestinal mucosal barrier damaged by cisplatin (CIS). Additionally, WTX restored the number of glial cells diminished by inflammatory damage, and ameliorated the serotoninergic neuronal dysfunction caused by insufficient secretion of glia-derived neurotrophic factor (GDNF), and enhanced intestinal transit. CONCLUSIONS In this study, a total of 100 components of the WTX extract were identified through literature review and mass spectrometry database search. Utilizing computer technology, in conjunction with pharmacodynamic and mechanistic studies, WTX has been found to restore serotoninergic neuronal function by reducing intestinal mucosal inflammatory and oxidative damage, ultimately promoting intestinal transport and treating dyspepsia.
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Affiliation(s)
- Xiaoying Zhang
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China; College of Pharmacy, Hebei University of Chinese Medicine, Xingyuan Road 3, Shijiazhuang, 050200, China
| | - Shiyu Wang
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Jinyu Xie
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Jinyu Wang
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Yaru Gu
- College of Pharmacy, Hebei University of Chinese Medicine, Xingyuan Road 3, Shijiazhuang, 050200, China
| | - Bo Wu
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Yixin Zhang
- College of Pharmacy, Hebei University of Chinese Medicine, Xingyuan Road 3, Shijiazhuang, 050200, China; International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Shijiazhuang, 050091, China
| | - Tingxu Yan
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China.
| | - Ying Jia
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China.
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Liang C, Wei S, Ji Y, Lin J, Jiao W, Li Z, Yan F, Jing X. The role of enteric nervous system and GDNF in depression: Conversation between the brain and the gut. Neurosci Biobehav Rev 2024; 167:105931. [PMID: 39447778 DOI: 10.1016/j.neubiorev.2024.105931] [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] [Received: 06/26/2024] [Revised: 10/14/2024] [Accepted: 10/20/2024] [Indexed: 10/26/2024]
Abstract
Depression is a debilitating mental disorder that causes a persistent feeling of sadness and loss of interest. Approximately 280 million individuals worldwide suffer from depression by 2023. Despite the heavy medical and social burden imposed by depression, pathophysiology remains incompletely understood. Emerging evidence indicates various bidirectional interplay enable communication between the gut and brain. These interplays provide a link between intestinal and central nervous system as well as feedback from cortical and sensory centers to enteric activities, which also influences physiology and behavior in depression. This review aims to overview the significant role of the enteric nervous system (ENS) in the pathophysiology of depression and gut-brain axis's contribution to depressive disorders. Additionally, we explore the alterations in enteric glia cells (EGCs) and glial cell line-derived neurotrophic factor (GDNF) in depression and their involvement in neuronal support, intestinal homeostasis maintains and immune response activation. Modulating ENS function, EGCs and GDNF level could serve as novel strategies for future antidepressant therapy.
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Affiliation(s)
- Chuoyi Liang
- School of Nursing, Jinan University, Guangzhou, China
| | - Sijia Wei
- School of Nursing, Jinan University, Guangzhou, China
| | - Yelin Ji
- School of Nursing, Jinan University, Guangzhou, China
| | - Jiayi Lin
- School of Nursing, Jinan University, Guangzhou, China
| | - Wenli Jiao
- School of Nursing, Jinan University, Guangzhou, China
| | - Zhiying Li
- School of Nursing, Jinan University, Guangzhou, China
| | - Fengxia Yan
- School of Nursing, Jinan University, Guangzhou, China.
| | - Xi Jing
- School of Nursing, Jinan University, Guangzhou, China; Guangdong-Hong Kong-Macau Great Bay Area Geoscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou, China.
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Jiang S, Pei L, Chen L, Sun J, Song Y. Mechanisms of Electroacupuncture in Alleviating Visceral Hypersensitivity in Post-Infectious Irritable Bowel Syndrome Mice: The Role of GDNF Signaling Pathway and Gut Microbiota. Microb Physiol 2024; 34:255-263. [PMID: 39396501 DOI: 10.1159/000541888] [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] [Received: 11/09/2023] [Accepted: 10/07/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Post-infectious irritable bowel syndrome (PI-IBS) is a functional bowel disease that develops following an acute gastrointestinal infection. Electroacupuncture (EA) can regulate the gut microbiota and alleviate visceral hypersensitivity. Glial cell-derived neurotrophic factor (GDNF) is a potential factor in visceral hypersensitivity reactions. The aim of this study was to explore whether EA could alleviate visceral hypersensitivity in PI-IBS by regulating gut microbiota through GDNF signaling. METHODS 2,4,6-trinitrobenzene sulfonic acid was used to induce visceral hypersensitivity in PI-IBS mice. Intestinal visceral sensitivity was assessed by using the abdominal withdrawal reflex (colorectal distention). 16S ribosomal RNA sequencing profiles the gut microbiome community. RESULTS GDNF can exacerbate the imbalances of the gut microbiota and increase visceral hypersensitivity compared with the model group. Whereas EA treatment increases the richness and diversity of the gut microbiota, decreases differences among species and alleviates visceral sensitivity. CONCLUSION EA can alleviate visceral hypersensitivity in PI-IBS by regulating the gut microbiota via GDNF signaling, providing new insights for mechanistic research on EA in PI-IBS treatment.
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Affiliation(s)
- Shiyuan Jiang
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China,
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China,
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China,
| | - Lixia Pei
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lu Chen
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianhua Sun
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yafang Song
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China
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Gorini F, Tonacci A. Vitamin D: An Essential Nutrient in the Dual Relationship between Autoimmune Thyroid Diseases and Celiac Disease-A Comprehensive Review. Nutrients 2024; 16:1762. [PMID: 38892695 PMCID: PMC11174782 DOI: 10.3390/nu16111762] [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] [Received: 05/11/2024] [Revised: 05/29/2024] [Accepted: 06/03/2024] [Indexed: 06/21/2024] Open
Abstract
Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants are probably involved. Celiac disease (CeD) also represents a public concern, given its increasing prevalence due to the recent improvement of screening programs, leading to the detection of silent subtypes. The two conditions may be closely associated due to common risk factors, including genetic setting, changes in the composition and diversity of the gut microbiota, and deficiency of nutrients like vitamin D. This comprehensive review discussed the current evidence on the pivotal role of vitamin D in modulating both gut microbiota dysbiosis and immune system dysfunction, shedding light on the possible relevance of an adequate intake of this nutrient in the primary prevention of AITD and CeD. While future technology-based strategies for proper vitamin D supplementation could be attractive in the context of personalized medicine, several issues remain to be defined, including standardized assays for vitamin D determination, timely recommendations on vitamin D intake for immune system functioning, and longitudinal studies and randomized controlled trials to definitely establish a causal relationship between serum vitamin D levels and the onset of AITD and CeD.
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Affiliation(s)
- Francesca Gorini
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy;
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Wanyi Z, Jiao Y, Wen H, Bin X, Xuefei W, Lan J, Liuyin Z. Bidirectional communication of the gut-brain axis: new findings in Parkinson's disease and inflammatory bowel disease. Front Neurol 2024; 15:1407241. [PMID: 38854967 PMCID: PMC11157024 DOI: 10.3389/fneur.2024.1407241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/13/2024] [Indexed: 06/11/2024] Open
Abstract
Parkinson's disease (PD) and inflammatory bowel disease (IBD) are the two chronic inflammatory diseases that are increasingly affecting millions of people worldwide, posing a major challenge to public health. PD and IBD show similarities in epidemiology, genetics, immune response, and gut microbiota. Here, we review the pathophysiology of these two diseases, including genetic factors, immune system imbalance, changes in gut microbial composition, and the effects of microbial metabolites (especially short-chain fatty acids). We elaborate on the gut-brain axis, focusing on role of gut microbiota in the pathogenesis of PD and IBD. In addition, we discuss several therapeutic strategies, including drug therapy, fecal microbiota transplantation, and probiotic supplementation, and their potential benefits in regulating intestinal microecology and relieving disease symptoms. Our analysis will provide a new understanding and scientific basis for the development of more effective therapeutic strategies for these diseases.
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Affiliation(s)
- Zhang Wanyi
- Department of Neurology, Chongqing Emergency Medical Center, Chongging University Central Hospital, Chongqing, China
| | - Yan Jiao
- Department of Nursing, Chongqing Emergency Medical Center, Chongging University Central Hospital, Chongqing, China
| | - Huang Wen
- Department of Neurology, Chongqing Emergency Medical Center, Chongging University Central Hospital, Chongqing, China
| | - Xu Bin
- Outpatient Department, Chongqing Emergency Medical Center, Chongging University Central Hospital, Chongqing, China
| | - Wang Xuefei
- Department of Neurology, Chongqing Emergency Medical Center, Chongging University Central Hospital, Chongqing, China
| | - Jiang Lan
- Outpatient Department, Chongqing Emergency Medical Center, Chongging University Central Hospital, Chongqing, China
| | - Zhou Liuyin
- Department of Respiratory Medicine, Chongqing Emergency Medical Center, Chongging University Central Hospital, Chongqing, China
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Thomasi B, Valdetaro L, Ricciardi MC, Gonçalves de Carvalho M, Fialho Tavares I, Tavares-Gomes AL. Enteric glia as a player of gut-brain interactions during Parkinson's disease. Front Neurosci 2023; 17:1281710. [PMID: 38027511 PMCID: PMC10644407 DOI: 10.3389/fnins.2023.1281710] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
The enteric glia has been shown as a potential component of neuroimmune interactions that signal in the gut-brain axis during Parkinson's disease (PD). Enteric glia are a peripheral glial type found in the enteric nervous system (ENS) that, associated with enteric neurons, command various gastrointestinal (GI) functions. They are a unique cell type, with distinct phenotypes and distribution in the gut layers, which establish relevant neuroimmune modulation and regulate neuronal function. Comprehension of enteric glial roles during prodromal and symptomatic phases of PD should be a priority in neurogastroenterology research, as the reactive enteric glial profile, gastrointestinal dysfunction, and colonic inflammation have been verified during the prodromal phase of PD-a moment that may be interesting for interventions. In this review, we explore the mechanisms that should govern enteric glial signaling through the gut-brain axis to understand pathological events and verify the possible windows and pathways for therapeutic intervention. Enteric glia directly modulate several functional aspects of the intestine, such as motility, visceral sensory signaling, and immune polarization, key GI processes found deregulated in patients with PD. The search for glial biomarkers, the investigation of temporal-spatial events involving glial reactivity/signaling, and the proposal of enteric glia-based therapies are clearly demanded for innovative and intestine-related management of PD.
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Affiliation(s)
- Beatriz Thomasi
- Department of Physiology, Michigan State University, East Lansing, MI, United States
| | - Luisa Valdetaro
- Department of Molecular Pathobiology, NYU College of Dentistry, New York, NY, United States
| | - Maria Carolina Ricciardi
- Neuroglial Interaction Lab, Neuroscience Program, Universidade Federal Fluminense, Niterói, Brazil
| | | | - Isabela Fialho Tavares
- Neuroglial Interaction Lab, Neurobiology Department, Universidade Federal Fluminense, Niterói, Brazil
| | - Ana Lucia Tavares-Gomes
- Neuroglial Interaction Lab, Neuroscience Program, Universidade Federal Fluminense, Niterói, Brazil
- Neuroglial Interaction Lab, Neurobiology Department, Universidade Federal Fluminense, Niterói, Brazil
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Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum. NPJ Biofilms Microbiomes 2022; 8:50. [PMID: 35768415 PMCID: PMC9243078 DOI: 10.1038/s41522-022-00312-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 05/31/2022] [Indexed: 11/08/2022] Open
Abstract
Bifidobacterium spp. are abundant gut commensals, especially in breast-fed infants. Bifidobacteria are associated with many health-promoting effects including maintenance of epithelial barrier and integrity as well as immunomodulation. However, the protective mechanisms of bifidobacteria on intestinal epithelium at molecular level are poorly understood. In this study, we developed a high-throughput in vitro screening assay to explore binding receptors of intestinal epithelial cells for Bifidobacterium bifidum. Short interfering RNAs (siRNA) were used to silence expression of each gene in the Caco-2 cell line one by one. The screen yielded four cell surface proteins, SERPINB3, LGICZ1, PKD1 and PAQR6, which were identified as potential receptors as the siRNA knock-down of their expression decreased adhesion of B. bifidum to the cell line repeatedly during the three rounds of siRNA screening. Furthermore, blocking of these host cell proteins by specific antibodies decreased the binding of B. bifidum significantly to Caco-2 and HT29 cell lines. All these molecules are located on the surface of epithelial cells and three out of four, SERPINB3, PKD1 and PAQR6, are involved in the regulation of cellular processes related to proliferation, differentiation and apoptosis as well as inflammation and immunity. Our results provide leads to the first steps in the mechanistic cascade of B. bifidum-host interactions leading to regulatory effects in the epithelium and may partly explain how this commensal bacterium is able to promote intestinal homeostasis.
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Liu C, Yang J. Enteric Glial Cells in Immunological Disorders of the Gut. Front Cell Neurosci 2022; 16:895871. [PMID: 35573829 PMCID: PMC9095930 DOI: 10.3389/fncel.2022.895871] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 04/07/2022] [Indexed: 11/13/2022] Open
Abstract
Enteric glial cells (EGCs) are one of the major cell types of neural crest lineage distributed in the gastrointestinal tract. EGCs represent an integral part of the enteric nervous system (ENS) and significantly outnumber ENS neurons. Studies have suggested that EGCs would exert essential roles in supporting the survival and functions of the ENS neurons. Notably, recent evidence has begun to reveal that EGCs could possess multiple immune functions and thereby may participate in the immune homeostasis of the gut. In this review article, we will summarize the current evidence supporting the potential involvement of EGCs in several important immunological disorders, including inflammatory bowel disease, celiac disease, and autoimmune enteropathy. Further, we highlight critical questions on the immunological aspects of EGCs that warrant future research attention.
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Affiliation(s)
- Chang Liu
- Center for Life Sciences, Peking University, Beijing, China
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
- College of Life Sciences, Wuhan University, Wuhan, China
| | - Jing Yang
- Center for Life Sciences, Peking University, Beijing, China
- State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China
- IDG/McGovern Institute for Brain Research, Peking University, Beijing, China
- Chinese Institute for Brain Research, Beijing, China
- Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China
- *Correspondence: Jing Yang
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Fu Z, Yang H, Xiao Y, Wang X, Yang C, Lu L, Wang W, Lyu W. Ileal Microbiota Alters the Immunity Statues to Affect Body Weight in Muscovy Ducks. Front Immunol 2022; 13:844102. [PMID: 35222437 PMCID: PMC8866836 DOI: 10.3389/fimmu.2022.844102] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 01/17/2022] [Indexed: 12/22/2022] Open
Abstract
The ileum is mainly responsible for food absorption and nutrients transportation. The microbes in its intestinal lumen play an essential role in the growth and health of the host. However, it is still unknown how the ileal microbes affect the body weight of the host. In this study, we used Muscovy ducks as an animal model to investigate the relationship between the ileal microbes and body weight and further explore the potential mechanism. The ileum tissue and ileal contents of 200 Muscovy ducks were collected for mRNA extraction and real-time quantitative PCR, as well as DNA separation and 16S rRNA gene sequencing. With body weight being ranked, the bottom 20% (n = 40) and top 20% (n = 40) were set as the low and high groups, respectively. Our results showed that in the ileum of Muscovy ducks, the Bacteroides, Firmicutes, and Proteobacteria were the predominant phyla with the 10 most abundant genera, namely Candidatus Arthromitus, Bacteroides, Streptococcus, Vibrio, Romboutsia, Cetobacterium, Clostridium sensu stricto 1, Terrisporobacter, Escherichia-Shigella, and Lactobacillus. We identified Streptococcus, Escherichia-Shigella, Candidatus Arthromitus, Bacteroides, Faecalibacterium, and Oscillospira were closely correlated to the growth of Muscovy ducks. Streptococcus and Escherichia-Shigella were negatively related to body weight (BW), while Candidatus Arthromitus, Bacteroides, Faecalibacterium, and Oscillospira were positively associated with BW. In addition, we found that the relative expression levels of tight junction proteins (Claudin 1, Claudin 2, ZO-1 and ZO-2) in the high group showed an upward trend, although this trend was not significant (P > 0.05). The expression of pro-inflammatory factors (IL-1β, IL-2 and TNF-α) decreased in the high group, while the anti-inflammatory factor IL-10 increased. Of course, except IL-2, these differences were not significant (P > 0.05). Finally, the correlation analysis showed that Escherichia-Shigella was significantly positively correlated with IL-1β (P < 0.05). These findings may provide fundamental data for the development of next-generation probiotics and assist the development of strategies for changing the gut microbiota to promote the growth performance in the duck industry.
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Affiliation(s)
- Zixian Fu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.,College of Animal Science, Zhejiang A&F University, Hangzhou, China
| | - Hua Yang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Yingping Xiao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Xiaoli Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Caimei Yang
- College of Animal Science, Zhejiang A&F University, Hangzhou, China
| | - Lizhi Lu
- Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Wen Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Wentao Lyu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
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Liu W, Zhou T, Tian J, Yu X, Ren C, Cao Z, Hou P, Zhang Q, Li A. Role of GDNF, GFRα1 and GFAP in a Bifidobacterium-Intervention Induced Mouse Model of Intestinal Neuronal Dysplasia. Front Pediatr 2022; 9:795678. [PMID: 35096711 PMCID: PMC8796853 DOI: 10.3389/fped.2021.795678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/20/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE To investigate the effects of glial cell-derived neurotrophic factor (GDNF), GDNF family receptor alpha 1 (GFRα1), and glial fibrillary acidic protein (GFAP) on colonic motility in a mouse model of intestinal neuronal dysplasia by intervention with Bifidobacterium and to explore the influence of Bifidobacterium on enteric glial cells (EGCs). METHODS Western blotting and qRT-PCR were employed to detect the expression of GFRα1 and GFAP in colonic tissues of mice with or without Tlx2 mutations, and ELISA was used to detect the expression of GDNF in serum. IHC was used to detect the appearance of the ganglion cells. Subsequently, Tlx2 homozygous mutant (Tlx2-/-) mice were treated with Bifidobacterium. Colonic motility was measured before and after intervention by measuring the glass bead expelling time. The variations in abdominal circumference and GDNF, GFRα1, and GFAP expression were measured. In addition, 16SrRNA gene sequencing was performed to detect the abundance of the intestinal microbiota. RESULTS The mRNA and protein expression of GFRα1 and GFAP was decreased in the colonic tissues of Tlx2-/- mice and GDNF expression was decreased in serum compared with Tlx2+/- and WT mice. After confirming the colonization of Bifidobacterium by 16S rRNA gene sequencing, the expelling time and abdominal distension were ameliorated, and the expression of GFAP, GDNF, and GFRα1 was increased. CONCLUSIONS The expression of GDNF, GFRα1, and GFAP is associated with colonic motility. The altered expression of EGC-related factors suggested that Bifidobacterium may be involved in the EGC activation process. The amelioration of IND symptoms after intervention with Bifidobacterium prompted the elicitation of adjuvant therapy.
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Affiliation(s)
- Wei Liu
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Tingting Zhou
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jinqiu Tian
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaofang Yu
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chuantao Ren
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Pediatric Surgery, Dezhou People's Hospital, Dezhou, China
| | - Zengcai Cao
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Peimin Hou
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Qiangye Zhang
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Aiwu Li
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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Nutraceuticals and Enteric Glial Cells. Molecules 2021; 26:molecules26123762. [PMID: 34205534 PMCID: PMC8234579 DOI: 10.3390/molecules26123762] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/11/2021] [Accepted: 06/15/2021] [Indexed: 12/21/2022] Open
Abstract
Until recently, glia were considered to be a structural support for neurons, however further investigations showed that glial cells are equally as important as neurons. Among many different types of glia, enteric glial cells (EGCs) found in the gastrointestinal tract, have been significantly underestimated, but proved to play an essential role in neuroprotection, immune system modulation and many other functions. They are also said to be remarkably altered in different physiopathological conditions. A nutraceutical is defined as any food substance or part of a food that provides medical or health benefits, including prevention and treatment of the disease. Following the description of these interesting peripheral glial cells and highlighting their role in physiological and pathological changes, this article reviews all the studies on the effects of nutraceuticals as modulators of their functions. Currently there are only a few studies available concerning the effects of nutraceuticals on EGCs. Most of them evaluated molecules with antioxidant properties in systemic conditions, whereas only a few studies have been performed using models of gastrointestinal disorders. Despite the scarcity of studies on the topic, all agree that nutraceuticals have the potential to be an interesting alternative in the prevention and/or treatment of enteric gliopathies (of systemic or local etiology) and their associated gastrointestinal conditions.
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Wang X, Jia Y, Wen L, Mu W, Wu X, Liu T, Liu X, Fang J, Luan Y, Chen P, Gao J, Nguyen KA, Cui J, Zeng G, Lan P, Chen Q, Cheng B, Wang Z. Porphyromonas gingivalis Promotes Colorectal Carcinoma by Activating the Hematopoietic NLRP3 Inflammasome. Cancer Res 2021; 81:2745-2759. [PMID: 34003774 DOI: 10.1158/0008-5472.can-20-3827] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 02/11/2021] [Accepted: 03/16/2021] [Indexed: 11/16/2022]
Abstract
Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various digestive cancers. However, whether P. gingivalis can promote colorectal cancer and the underlying mechanism associated with such promotion remains unclear. In this study, we found that P. gingivalis was enriched in human feces and tissue samples from patients with colorectal cancer compared with those from patients with colorectal adenoma or healthy subjects. Cohort studies demonstrated that P. gingivalis infection was associated with poor prognosis in colorectal cancer. P. gingivalis increased tumor counts and tumor volume in the ApcMin/+ mouse model and increased tumor growth in orthotopic rectal and subcutaneous carcinoma models. Furthermore, orthotopic tumors from mice exposed to P. gingivalis exhibited tumor-infiltrating myeloid cell recruitment and a proinflammatory signature. P. gingivalis promoted colorectal cancer via NLRP3 inflammasome activation in vitro and in vivo. NLRP3 chimeric mice harboring orthotopic tumors showed that the effect of NLRP3 on P. gingivalis pathogenesis was mediated by hematopoietic sources. Collectively, these data suggest that P. gingivalis contributes to colorectal cancer neoplasia progression by activating the hematopoietic NLRP3 inflammasome. SIGNIFICANCE: This study demonstrates that the periodontal pathogen P. gingivalis can promote colorectal tumorigenesis by recruiting myeloid cells and creating a proinflammatory tumor microenvironment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2745/F1.large.jpg.
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Affiliation(s)
- Xi Wang
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Yiqun Jia
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.,Stomatology Center, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China
| | - Liling Wen
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Wenxin Mu
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Xianrui Wu
- Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tao Liu
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
| | - Xiangqi Liu
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Juan Fang
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Yizhao Luan
- State Key Laboratory of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Ping Chen
- Department of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Jinlong Gao
- Institute of Dental Research, Sydney Dental School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Ky-Anh Nguyen
- Institute of Dental Research, Sydney Dental School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Jun Cui
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
| | - Gucheng Zeng
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Ping Lan
- Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qianming Chen
- The Affiliated Hospital of Stomatology, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Bin Cheng
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
| | - Zhi Wang
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
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Gong B, Wang C, Meng F, Wang H, Song B, Yang Y, Shan Z. Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2021; 12:774362. [PMID: 34867823 PMCID: PMC8635774 DOI: 10.3389/fendo.2021.774362] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 10/29/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID. METHODS We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD. RESULTS The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto's thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves' disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls. CONCLUSIONS This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels. SYSTEMATIC REVIEW REGISTRATION PROSPERO, identifier CRD42021251557.
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