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brain-gut axis in the pathogenesis of Helicobacter pylori infection

World Journal of Gastroenterology 2014年第18期20卷 5212-5225页

作者： Jacek Budzyński Maria Kopocka Clinical Ward of Vascular Diseases and Internal Medicine The Jan Biziel University Hospital No.2Nicolaus Copernicus University in ToruńCollegium Medicum85-168 BydgoszczPoland Department of Gastroenterological Nursing Nicolaus Copernicus University in ToruńCollegium Medicum85-168 BydgoszczPoland

Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis, similar to other microorganisms present in the alimentary tract. The brain-gut axis integrates the central, peripheral, enteric and autonomic nervous systems, as well as the endocrine and immunological systems, with gastrointestinal functions and environmental stimuli, including gastric and intestinal microbiota. The bidirectional relationship between H. pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it, resulting in alterations in cognitive functions, food intake and appetite, immunological response, and modification of symptom sensitivity thresholds. Furthermore, disturbances in the upper and lower digestive tract permeability, motility and secretion can occur, mainly as a form of irritable bowel syndrome. Many of these abnormalities disappear following H. pylori eradication. H. pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes, or by microelement deficiency secondary to functional and morphological changes in the digestive tract. In digestive tissue, H. pylori can alter signaling in the brain-gut axis by mast cells, the main brain-gut axis effector, as H. pylori infection is associated with decreased mast cell infiltration in the digestive tract. Nevertheless, unequivocal data concerning the direct and immediate effect of H. pylori infection on the brain-gut axis are still lacking. Therefore, further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H. pylori infection pathophysiology and suggest new therapeutic approaches.

关键词： Helicobacter pylori brain-gut axis Behavior Motility Gastric acid Visceral hypersensitivity

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New technologies to investigate the brain-gut axis

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World Journal of Gastroenterology 2009年第2期15卷 182-191页

作者： Abhishek Sharma Dina Lelic Christina Brock Peter Paine Qasim Aziz Department of Gastrointestinal Science University of Manchester Manchester M13 9PL United Kingdom Neurogastro-enterology Group Wingate Institute of Neurogastroenterology Barts and the London School of Medicine and Dentistry London E1 2AJ United Kingdom Mech-Sense Department of Gastroenterology Aalborg Hospital Boulevarden 13 DK-9000 Aalborg Denmark

Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission Tomography, Magnetoencephalography, and Electroencephalography （EEG）. Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways （primary afferents, spinal and supraspinal transmission）, brainimaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal disorders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the phenotypic differences that determine an individual＇s response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual＇s psychological, autonomic, neuroendocrine, neurophysiological, and genetic profile to define phenotypic traits that may be at greater risk of developing sensitised states in response to gut inflammation or injury.

关键词： brain-gut axis Central processing Neuraxis Neurophysiology

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Effects of electroacupuncture on c-Fos expression in the spinal cord and brain of rats with chronic visceral hypersensitivity

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Neural Regeneration Research 2009年第5期4卷 339-343页

作者： Xiaomei Wang Huirong Liu Guanghong Ding Yunfei Chen Huangan Wu Na Li Enhua Zhou Xiudi Qin Lingsong Yuan Department of Mechanics and Engineering Science Fudan University Shanghai 200433 China Key Laboratory of Acupuncture-Moxibustion and Immunological Effects Shanghai University of Traditional Chinese Medicine Shanghai 201203 China

BACKGROUND： Visceral hypersensitivity is the main cause of irritable bowel syndrome, c-Fos is a marker of visceral hypersensitivity in the central nervous system. Electroacupuncture can relieve chronic visceral hypersensitivity in rats, but the mechanism is still unknown. OBJECTIVE： To identify c-Fos expression in the spinal cord and cerebral cortex of rats with chronic visceral hypersensitivity, and to test the effects of electroacupuncture on pain sensitivity in rats with chronic visceral hypersensitivity. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the Animal E：~perimental Center, Shanghai University of Traditional Chinese Medicine, from January to April, 2007. MATERIALS： A total of 24 neonatal, male, Sprague Dawley rats, aged five days old, were equally and randomly assigned into a normal group, a model group, and an electroacupuncture group. Rabbit anti-rat c-Fos antibody and Evision secondary antibody kits （Sigma, USA）, diaminobenzidine kit （Dako, Denmark）, and an LD202H electroacupuncture apparatus （Huawei, Beijing, China） were used in this study. METHODS： Neonatal rats from the model and electroacupuncture groups were used to establish rat models of chronic visceral hypersensitivity by the saccule stimulation method. After model establishment, 0.25 mm diameter electric needles were inserted into Tianshu （ST 25） and Shangjuxu （ST37） at a depth of approximately 0.5 cm, with an square wave （alternating current frequency at 100/20 Hz, amplitude ranged 0.2-0.6 ms, intensity at 1 mA） once for 20 minutes, once a day, for seven days. Rats in the normal and model groups were not treated. MAIN OUTCOME MEASURES： Following 7 days of treatment, c-Fos expression in the spinal cord and cerebral cortex was detected by immunohistochemistry. After the first electroacupuncture treatment, abdominal withdrawal reflex scores were investigated to evaluate the pain threshold for chronic visceral hypersensitivity in rats. RESULTS： Visceral hy

关键词： electroacupuncture chronic visceral hypersensitivity irritable bowel syndrome brain-gut axis c-Fos

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Oral nano-antioxidants improve sleep by restoring intestinal barrier integrity and preventing systemic inflammation

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National Science Review 2023年第12期10卷 70-82页

作者： Zhanfeng Wu Lei Liu Lei Li Xinran Cao Wang Jia Xiaodan Liao Zhongpu Zhao Hedong Qi Guoqiang Fan Huiqiang Lu Chunying Shu Mingming Zhen Chunru Wang Chunli Bai Beijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology CAS ResearchEducation Center for Excellence in Molecular Sciences Institute of Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences School of Pharmacy Wenzhou Medical University Center for Drug Screening and Research School of Geography and Environmental Engineering Gannan Normal University

Sleep deprivation(SD) is a severe public health threat that can cause systemic inflammation and nerve damage. Few effective and side-effect-free drugs are available to address SD. However, the bidirectional communications between the brain and gut provide new strategies for anti-SD therapeutics. Here we explored oral delivery of fullerene nano-antioxidants(FNAO) in the SD model to improve sleep by regulating abnormal intestinal barrier and systemic inflammation via the brain-gut axis. SD caused excessive reactive oxygen species(ROS) production and hyperactive inflammatory responses in the intestines of zebrafish and mouse models, leading to disturbed sleep patterns and reduced brain nerve activity. Of note,based on the property of the conjugated π bond of the C60structure to absorb unpaired electrons, oral FNAO efficiently reduced the excessive ROS in the intestines, maintained redox homeostasis and intestinal barrier integrity, and ameliorated intestinal and systemic inflammation, resulting in superior sleep improvement. Our findings suggest that maintaining intestinal homeostasis may be a promising avenue for SD-related nerve injury therapy.

关键词： sleep deprivation fullerene nano-antioxidants brain-gut axis reactive oxygen species inflammation

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Diet and physical activity influence the composition of gut microbiota,benefit on Alzheimer's disease

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Food Science and Human Wellness 2024年第2期13卷 541-555页

作者： Jinyue Zhou Min Tang Wanyi Li Rui Fang Chunlan Tang Qinwen Wang 无 School of Public Health Health Science CenterNingbo UniversityNingbo 315211China Department of Neurology Ningbo Rehabilitation HospitalNingbo 3151000China Ningbo Institute of Life and Health Industry University of Chinese Academy of SciencesNingbo 315100China Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province Ningbo 315100China

Alzheimer's disease is a neurodegenerative disease with complex *** microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's ***,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut *** demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity ***,the present study reviews the association between these two interventions and gut microbiota in the human *** also summarizes how these two interventions benefit Alzheimer's ***,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.

关键词： Alzheimer’s disease gut microbiota brain-gut axis Diet Physical activity

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Functional findings in irritable bowel syndrome

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World Journal of Gastroenterology 2006年第18期12卷 2830-2838页

作者： Iris Posserud Amanda Ersryd Magnus Simrén Department of Internal Medicine Sahlgrenska University HospitalGteborgSweden

The pathophysiology of IBS is complex and still incompletely known. Both central and peripheral factors, including psychosocial factors, abnormal GI motility and secretion, and visceral hypersensitivity, are thought to contribute to the symptoms of IBS. Several studies have demonstrated altered GI motor function in IBS patients and the pattern differs between IBS subgroups based on the predominant bowel pattern. Few studies have so far addressed GI secretion in IBS, but there are some evidence supporting altered secretion in the small intestine of IBS patients. Visceral hypersensitivity is currently considered to be perhaps the most important pathophysiological factor in IBS. Importantly, several external and internal factors can modulate visceral sensitivity, as well as GI motility, and enhanced responsiveness within the GI tract to for instance stress and nutrients has been demonstrated in IBS patients. Today IBS is viewed upon as a disorder of dysregulation of the so-called brain-gut axis, involving abnormal function in the enteric, autonomic and/or central nervous systems, with peripheral alterations probably dominating in some patients and disturbed central processing of signals from the periphery in others.

关键词： IBS Gastrointestinal motility Visceral hypersensitivity Gastrointestinal secretion Intestinal gas brain-gut axis brain imaging Autonomic nervous system

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Nutrition in Alzheimer's disease:a review of an underappreciated pathophysiological mechanism

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Science China(Life Sciences) 2023年第10期66卷 2257-2279页

作者： Jiwei Jiang Hanping Shi Shirui Jiang Anxin Wang Xinying Zou Yanli Wang Wenyi Li Yuan Zhang Mengfan Sun Qiwei Ren Jun Xu Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China China National Clinical Research Center for Neurological Diseases Beijing 100070China Department of Gastrointestinal Surgery Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Department of Clinical Nutrition Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing 100038China

Alzheimer's disease(AD)is the leading cause of dementia in older individuals and is an escalating challenge to global public *** therapy of AD is one of the well-funded areas;however,little progress has been made due to the complex *** evidence has demonstrated that modifying risk factors and lifestyle may prevent or delay the incidence of AD by 40%,which suggests that the management should pivot from single pharmacotherapy toward a multipronged approach because AD is a complex and multifaceted ***,the gut-microbiota-brain axis has gained tremendous traction in the pathogenesis of AD through bidirectional communication with multiple neural,immune,and metabolic pathways,providing new insights into novel therapeutic *** nutrition is an important and profound environmental factor that influences the composition and function of the *** Nutrition for Dementia Prevention Working Group recently found that dietary nutrition can affect cognition in AD-related dementia directly or indirectly through complex interactions of behavioral,genetic,systemic,and brain ***,considering the multiple etiologies of AD,nutrition represents a multidimensional factor that has a profound effect on AD onset and ***,mechanistically,the effect of nutrition on AD is uncertain;therefore,optimal strategies or the timing of nutritional intervention to prevent or treat AD has not been ***,this review summarizes the current state of knowledge concerning nutritional disorders,AD patient and caregiver burden,and the roles of nutrition in the pathophysiology of *** aim to emphasize knowledge gaps to provide direction for future research and to establish optimal nutrition-based intervention strategies for AD.

关键词： Alzheimer's disease nutrition diet pathogenesis metabolism brain-gut axis

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Association between inflammatory bowel diseases and Parkinson's disease: systematic review and meta-analysis

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Neural Regeneration Research 2022年第2期17卷 344-353页

作者： Yu Zhu Min Yuan Yue Liu Fang Yang Wen-Zhi Chen Zhen-Zhen Xu Zheng-Bing Xiang Ren-Shi Xu Department of Neurology Jiangxi Provincial People’s HospitalAffiliated People’s Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina

Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease(IBD) and Parkinson's disease(PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched Pub Med, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle–Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population(adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15–1.34, P 65 years old) IBD patients(adjusted HR = 1.32, 95% CI: 1.17–1.48) may have a higher risk than younger(≤ 65 years old) patients(adjusted HR = 1.24, 95% CI: 1.08–1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk(adjusted HR = 1.6, 95% CI: 1.2–2.2). Thus, our meta-analysis indicat

关键词： brain-gut axis central nervous system Crohn's disease inflammatory bowel diseases meta-analysis neurodegenerative disease neuroinflammation Parkinson's disease systematic review ulcerative colitis

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Pingwei capsules improve gastrointestinal motility in rats with functional dyspepsia

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Journal of Traditional Chinese Medicine 2018年第1期38卷 43-53页

作者： Liang Qiankun Mao Lanfang Du Xiaojuan Li Yunxia Yan Yuan Liang Jingjing Liu Junhong Wang Longde Li Hongfang partment of Physiology College of Basic Medicine Lanzhou University Lanzhou 730000 China Department of Gastroenterology Affiliated Hospital Gansu Chinese Medical College Lanzhou 730020 China Department of Physiology College of Basic Medicine Lanzhou University Lanzhou 730000 China Key Laboratory of Preclinical Study for New Drugs of Gansu Province Lanzhou 730000 China

OBJECTIVE: To investigate the mechanism of Ping-wei capsules(PWC) in improving gastrointestinal m otility in rats with functional dyspepsia(FD).METHODS: We established an FD model by stimu-lating semi-starvation rats via tail damping, provo-cation, and forced exercise fatigue. The FD model group was further divided into five groups accord-ing to the treatment received: normal saline, dom-peridone, low-dose PWC, mid-dose PWC, or highdose PWC. The effect of PWC on FD was evaluated by measuring gastrointestinal motility. Changes in leptin and cholecystokinin(CCK) were detected through enzyme-linked immunosorbent assay, re-verse transcription-polymerase chain reaction, and ***: PWC significantly increased gastrointesti-nal m otility in FD rats. Furthermore, PWC signifi-cantly increased CCK m RNA and protein concentra-tions in the duodenum and antrum, decreased leptin protein concentrations in the duodenum, an-trum, and hypothalamus, and decreased CCK pro-tein concentration in the ***: PWC improves gastrointestinal mo-tor function in FD rats by decreasing the leptin con-centration in serum and the brain-gut axis, and by increasing the CCK concentration in gastrointesti-nal tissue. Our findings help to elucidate the mech-anism of FD and provide further insight into the pharmacokinetics of PWC.

关键词： Pingwei capsule Dyspepsia Gastroin- testinal motility brain-gut peptide brain-gut axis

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Influence of gut microbiota on neuropsychiatric disorders

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World Journal of Gastroenterology 2017年第30期23卷 5486-5498页

作者： María Carmen Cenit Yolanda Sanz Pilar Codoner-Franch Nutrition and Health Research Group Institute of Agrochemistry and Food Technology National Research Council (IATA-CSIC) Department of Pediatrics Obstetrics and Gynecology University of Valencia Department of Pediatrics Dr. Peset University Hospital

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain(gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome(microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and the

关键词： Microbiota Microbiome Dysbiosis brain-gut axis Mental health Psychiatric conditions

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