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Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

Neural Regeneration Research 2024年第10期19卷 2219-2228页

作者： Paula Maria Neufeld Ralf A.Nettersheim Veronika Matschke Matthias Vorgerd Sarah Stahlke Carsten Theiss Department of Cytology Institute of AnatomyMedical FacultyRuhr-University BochumBochumGermany Department of Visceral Surgery University Hospital BergmannsheilRuhr-University BochumBochumGermany Department of Neurology Heimer Institute for Muscle ResearchUniversity Hospital BergmannsheilRuhr-University BochumBochumGermany

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurode

关键词： diet gut-brain axis microbiome neurodegenerative diseases nutrition Parkinson's disease progesterone steroid hormones

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Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

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Neural Regeneration Research 2024年第3期19卷 519-528页

作者： Xiaodi Xie Lei Wang Shanshan Dong ShanChun Ge Ting Zhu Institute of Neuroregeneration&Neurorehabilitation Department of PathophysiologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina School of Traditional Chinese Pharmacy China Pharmaceutical UniversityNanjingJiangsu ProvinceChina Department of Rehabilitation Medicine The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

关键词： enteric glia cells gut microbiota gut-brain axis immune response inflammation ischemic stroke lung-brain axis microglia

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gut flora in multiple sclerosis:implications for pathogenesis and treatment

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Neural Regeneration Research 2024年第7期19卷 1480-1488页

作者： Weiwei Zhang Ying Wang Mingqin Zhu Kangding Liu Hong-Liang Zhang Department of Neurology the First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Department of Life Sciences National Natural Science Foundation of ChinaBeijingChina

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

关键词： gut flora gut-brain axis multiple sclerosis pathogenesis treatment

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gut microbial regulation of innate and adaptive immunity after traumatic brain injury

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Neural Regeneration Research 2024年第2期19卷 272-276页

作者： Marta Celorrio Kirill Shumilov Stuart H.Friess Department of Pediatrics Washington University in St.Louis School of MedicineSt.LouisMOUSA

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

关键词： gut microbiome gut microbiota gut-brain axis macrophage microglia monocyte neuroinflammation short-chain fatty acids T cell traumatic brain injury

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Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

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Neural Regeneration Research 2024年第4期19卷 833-845页

作者： Xiaoyan Liu Yi Liu Junlin Liu Hantao Zhang Chaofan Shan Yinglu Guo Xun Gong Mengmeng Cui Xiubin Li Min Tang School of Life Sciences Jiangsu University Institute of Animal Husbandry Jiangsu Academy of Agricultural Sciences Department of Rheumatology&Immunology Affiliated Hospital of Jiangsu University Department of Neurology The Second Affiliated Hospital of Shandong First Medical University

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

关键词： biomarker diet pattern gut microbiota gut-brain axis metagenomics mitochondrial dysfunction multi-omics neurodegenerative disease neuroinflammation probiotic

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gut-brain axis:Focus on gut metabolites short-chain fatty acids

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World Journal of Clinical Cases 2022年第6期10卷 1754-1763页

作者： Cen Guo Ya-Jing Huo Yu Li Yan Han Da Zhou Department of Neurology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China Department of Gastroenterology and Hepatology Zhongshan HospitalFudan UniversityShanghai Institute of Liver DiseaseShanghai 200032China

Emerging evidence supports that the gut microbiome,reconsidered as a new organ in the human body,can not only affect the local gut,but also communicate with the brain via multiple pathways related to neuroendocrine,immune,and neural pathways,thereby proposing the new concept of the microbiome-gut-brain(MGB)axis.Recently,the role of short-chain fatty acids(SCFAs),which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis,has garnered significant attention.SCFAs are involved in a broad range of central neurological diseases,including neurodegenerative diseases,cerebral vascular diseases,epilepsy,neuroimmune inflammatory diseases,and mood disorders.However,the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated.Herein,we summarize current knowledge regarding interactions between SCFAs and the MGB axis,as well as their protective effects against central neurological diseases.

关键词： gut-brain axis Short-chain fatty acids Neurological disease Microbiome-gutbrain

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The gut brain Connection

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Journal of Behavioral and brain Science 2024年第3期14卷 103-117页

作者： Saeed Alzubide Muslih Alhalafi King Saud Medical City Riyadh Saudi Arabia Security Forces Hospital Riyadh Saudi Arabia

The gut-brain connection is a bidirectional communication system that links the gut microbiome to the central nervous system (CNS). The gut-brain axis communicates through a variety of mechanisms, including the release of hormones, neurotransmitters, and cytokines. These signaling molecules can travel from the gut to the brain and vice versa, influencing various physiological and cognitive functions. Emerging therapeutic strategies targeting the gut-brain connection include probiotics, prebiotics, and faecal microbiota transplantation (FMT). Probiotics are live microorganisms that are similar to the beneficial bacteria that are naturally found in the gut. Prebiotics are non-digestible fibers that feed the beneficial bacteria in the gut. FMT is a procedure in which faecal matter from a healthy donor is transplanted into the gut of a person with a diseased microbiome. Probiotics, prebiotics, and FMT have been shown to be effective in treating a variety of gastrointestinal disorders, and there is growing evidence that they may also be effective in treating neurological and psychiatric disorders. This review explores the emerging field of the gut-brain connection, focusing on the communication pathways between the gut microbiome and the central nervous system. We summarize the potential roles of gut dysbiosis in various neurological and psychiatric disorders. Additionally, we discuss potential therapeutic strategies, research limitations, and future directions in this exciting area of research. More research is needed to fully understand the mechanisms underlying the gut-brain connection and to develop safe and effective therapies that target this pathway. However, the findings to date are promising, and there is the potential to revolutionize the way we diagnose and treat a variety of neurological and psychiatric disorders.

关键词： gut-brain Connection gut-brain axis Enteric Nervous System Microbiota Neurotransmitters Neuroinflammation and Mental Health

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Update on the gut microbiome in health and diseases

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World Journal of Methodology 2024年第1期14卷 18-32页

作者： Maurizio Salvadori Giuseppina Rosso Department of Renal Transplantation Careggi University HospitalFlorence 50139TuscanyItaly Division of Nephrology San Giovanni di Dio HospitalFlorence 50143ToscanaItaly

The Human Microbiome Project,Earth Microbiome Project,and next-generation sequencing have advanced novel genome association,host genetic linkages,and pathogen identification.The microbiome is the sum of the microbes,their genetic information,and their ecological niche.This study will describe how millions of bacteria in the gut affect the human body in health and disease.The gut microbiome changes in relation with age,with an increase in Bacteroidetes and Firmicutes.Host and environmental factors affecting the gut microbiome are diet,drugs,age,smoking,exercise,and host genetics.In addition,changes in the gut microbiome may affect the local gut immune system and systemic immune system.In this study,we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases.Due to the high number of publications on the argument,from a methodologically point of view,we decided to select the best papers published in referred journals in the last 3 years.Then we selected the previously published papers.The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.

关键词： gut microbiome Dysbiosis Pathobionts gut-brain axis Heart-brain axis Metabolic diseases Omics techniques

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gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression-and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4801-4822页

作者： Kaikai Zhang Lijian Chen Jianzheng Yang Jiali Liu Jiahao Li Yi Liu Xiuwen Li Long Chen Clare Hsu Jiahao Zeng Xiaoli Xie Qi Wang Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification School of Forensic MedicineSouthern Medical UniversityGuangzhou 510515China Department of Toxicology School of Public HealthSouthern Medical University(Guangdong Provincial Key Laboratory of Tropical Disease Research)Guangzhou 510515China

Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms involved.Here,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the hippocampus.Mean-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in recipients.Further,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like behaviors.Finally,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of SCFAs.The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like behaviors.Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner.This study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.

关键词： Methamphetamine gut microbiota Short-chain fatty acids Sigma-1 receptor Mental disorders Colonic inflammation Intestinal barrier gut-brain axis

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Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism

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Chinese Journal of Natural Medicines 2023年第10期21卷 745-758页

作者： ZHOU Junchi FAN Qilin CAI Xiaoying ZHANG Youying HOU Yuanlong CAO Shuqi LIZiguang FENG Mengzhen WANG Qingqing ZHANG Jianbing WANG Guangi ZHENG Xiao HAO Haiping State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Laboratory of Metabolic Regulation and Drug Target Discovery School of PharmacyChina Pharmaceutical UniversityNanjing 210009China WanBangDe Pharmaceutical Group Co. Ltd.Wenlin 317500China

Depression is a mental disorder with high morbidity,disability and relapse rates.Ginkgo biloba extract(GBE),a traditional Chinese medicine,has a long history of clinical application in the treatment of cerebral and mental disorders,but the key mechanism remains incompletely understood.Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism.GBE protected against unpredictable mild stress(UMS)-induced despair,anxiety-like and social avoidance behavior in mice without sufficient brain distribution.Fecal microbiome transplantation transmitted,while antibiotic cocktail abrogated the protective effect of GBE.Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid(UDCA)in the effect of GBE.UDCA administration induced depression-like behavior in mice.Together,these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.

关键词： Ginkgo biloba extract Depression gut microbiome gut-brain axis Bile acid

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