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

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.

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

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 neurodegenerative diseases such as Parkinson's disease.

Functional gastrointestinal disorders and gut-brain axis: What does the future hold?

Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.

Focus on the gut-brain axis: multiple sclerosis, the intestinal barrier and the microbiome

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.

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

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.

Microbiota-gut-brain axis and its affect inflammatory bowel disease:Pathophysiological concepts and insights for clinicians

Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease(IBD)pathogenesis,with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves,by acting on the different components of this system,mainly by modifying the microbiota.With the emergence of precision medicine,strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients.The aim of this narrative review is to elaborate on the concept of the gutbrain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature,and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.

Healthy axis: Towards an integrated view of the gut-brain health

Despite the lack of precise mechanisms of action, a growing number of studies suggests that gut microbiota is involved in a great number of physiological functions of the human organism. In fact, the composition and the relations of intestinal microbial populations play a role, either directly or indirectly, to both the onset and development of various pathologies. In particular, the gastrointestinal tract and nervous system are closely connected by the so-called gut–brain axis, a complex bidirectional system in which the central and enteric nervous system interact with each other, also engaging endocrine, immune and neuronal circuits. This allows us to put forward new working hypotheses on the origin of some multifactorial diseases: from eating to neuropsychiatric disorders (such as autism spectrum disorders and depression) up to diabetes and tumors (such as colorectal cancer). This scenario reinforces the idea that the microbiota and its composition represent a factor, which is no longer negligible, not only in preserving what we call “health” but also in defining and thus determining it. Therefore, we propose to consider the gut-brain axis as the focus of new scientific and clinical investigation as long as the locus of possible systemic therapeutic interventions.

Prion-like propagation of α-synuclein in gutbrain axis

Parkinson disease(PD) is a progressive degenerative disease of the nervous system,which is characterized by movement disorders,such as static tremor,rigidity,and bradykinesia in advanced patients.Gastrointestinal(GI) dysfunction,such as gastric dysmotility,constipation,and anorectic dysfunction,is common non-motor symptom in the early stage of PD.The progression of PD includes the degenerative loss of dopaminergic neurons and aggregation ofα-synuclein in the substantia nigra.Interestingly,both of them are also present in the enteric nervous system of PD patients.In this review,we describe the relationship between non-motor symptoms particularly GI dysfunction and the pathogenesis of PD,aiming to show the powerful evidences about the prion-like propagation of α-synuclein and support the hypothesis of gut-brain axis in PD.We then summarize the mechanism of the gut-brain axis and confirmα-synuclein as a potential target for drug design or new clinical treatment.

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

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.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

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.

Microphysiological systems for modeling gut-organ interaction

The gut is a digestive organ that absorbs nutrients but also plays a vital role in immune response and defense against external compounds.The complex interaction between the gut microbiota and other organs including the immune system of the host has been known in various contexts,yielding the notion of‘axes’between the gut and other organs.While the presence of various gut-organ axes has been reported,the lack of adequate in vitro model systems for studying this interaction has restricted a deeper insight into these phenomena.Recently developed microphysiological systems(MPS),also known as organ-on-a-chip,allow researchers to study complex interactions between diverse organs,and here we provide a review of how recently developed gut-on-a-chip systems are used for building models of various diseases that were difficult to study.

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

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.

Update on the gut microbiome in health and diseases

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.

The Gut Brain Connection

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.

Glyphosate Exposure Associated with Human Neurodegenerative Disorders: A Scoping Review

Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.

基于益气养阴法探讨参麦注射液调控肠道菌群-TMAO-炎症轴防治慢性心力衰竭的思路与策略

中医学将慢性心力衰竭(chronic heart failure, CHF)归属于“胸痹”“心悸”“水肿”“喘证”等范畴。气虚证、阴虚证贯穿CHF缓解阶段的始终,气阴两虚证为常见证型,益气养阴法为治疗CHF的重要方法之一。CHF的病情进展中,肠道菌群多样性的改变与炎症标志物相关,氧化三甲胺(trimethylamine N-oxide, TMAO)是炎症反应的关键调控因子,肠道菌群-TMAO-炎症轴可能是CHF发病的关键病理机制。因此,基于以上理论及研究基础,提出参麦注射液通过益气养阴法调控肠道菌群-TMAO-炎症轴,进而改善CHF心功能的研究假说。将中医学与微生态学相结合,对于阐释益气养阴法的作用机制具有重要的科学意义,从肠道微生态角度揭示益气养阴法的作用机制,以分子生物学语言描述“益气养阴”这一中医药治法,为益气养阴法防治CHF的深入研究提出新的思路和策略。

Gut microbiota in women:The secret of psychological and physical well-being

The gut microbiota works in unison with the host,promoting its health.In particular,it has been shown to exert protective,metabolic and structural functions.Recent evidence has revealed the influence of the gut microbiota on other organs such as the central nervous system,cardiovascular and the endocrine-metabolic systems and the digestive system.The study of the gut microbiota is outlining new and broader frontiers every day and holds enormous innovation potential for the medical and pharmaceutical fields.Prevention and treatment of specific women’s diseases involves the need to deepen the function of the gut as a junction organ where certain positive bacteria can be very beneficial to health.The gut microbiota is unique and dynamic at the same time,subject to external factors that can change it,and is capable of modulating itself at different stages of a woman’s life,playing an important role that arises from the intertwining of biological mechanisms between the microbiota and the female genital system.The gut microbiota could play a key role in personalized medicine.

柠条锦鸡儿生物量分配规律与异速生长对氮、磷添加的响应

氮(N)和磷(P)元素在生态系统的结构和功能、稳定性、服务价值和可持续发展中起着关键作用。但自工业革命以来,全球气候变化受人类活动影响愈加剧烈。气候变化不同程度的影响干旱和半干旱区的氮磷循环过程,进而改变植物个体生物量积累以及植被生产力。因此,探究荒漠植物的生物量积累与分配规律对氮、磷添加的响应机制,有助于深入理解干旱区植物应对大气氮磷沉降等气候变化的适应策略。以荒漠植物柠条锦鸡儿(Caragana korshinskii Kom.,以下简称柠条)为研究对象,通过养分添加控制实验研究柠条地上/地下生物量的积累和分配,揭示其异速生长规律。实验包括3种形态的氮素添加(NH_(4)^(+)、NH_(4)NO_(3)、NO_(3)^(-))和1种磷素添加(H_(2)PO_(4)^(-)),分别对应4个浓度梯度(4 g/m^(2)、8 g/m^(2)、16 g/m^(2)和32 g/m^(2))。结果表明,NO_(3)^(-)添加对柠条生物量有显著影响,但不同浓度对柠条生物量的影响无显著差异;单独的NH+4添加对柠条地上/地下部分生长都具有显著抑制作用,且抑制作用与添加浓度呈显著的正相关关系;NH_(4)NO_(3)添加初期对柠条地上/地下生物量均具有促进作用,但这种促进作用会随着柠条生长和后期NH_(4)NO_(3)添加浓度的增加而消失;高浓度NH4NO3添加量(32 g/m^(2))会抑制柠条的生长。低浓度(4 g/m^(2)、8 g/m^(2))外源氮添加会使柠条的生物量主要优先配给地下部分;磷添加则会使柠条的生物量分配策略向地上部分倾斜。综上所述,研究结果表明柠条改变地上和地下的生物量分配策略以响应氮或/和磷沉降。这一结论不仅增强了我们对植物生长策略的认识,而且有助于我们揭示全球气候变化条件下干旱地区土壤与植物之间的氮、磷循环和转化。

The role of gut microbiota in the gut-brain axis:current challenges and perspectives

Brain and the gastrointestinal(GI)tract are intimately con-nected to form a bidirectional neurohumoral communica-tion system.The communication between gut and brain,knows as the gut-brain axis,is so well established that the functional status of gut is always related to the condi-tion of brain.The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract.However,recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes.These recent fi ndings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis.To elucidate the role of gut microbiota in the gut-brain axis,precise identification of the composition of microbes constituting gut microbiota is an essential step.However,identifi cation of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the diffi culties in culture of gut microbes.Current methods for identifi ca-tion of microbes constituting gut microbiota are depend-ent on omics analysis methods by using advanced high tech equipment.Here,we review the association of gut microbiota with the gut-brain axis,including the pros and cons of the current high throughput methods for identi-fi cation of microbes constituting gut microbiota to eluci-date the role of gut microbiota in the gut-brain axis.

Microbiota and depression an update

The highest rates of morbidity and impairment related to gastrointestinal difficulties are associated with depression,which is associated with the highest rates of all mental disorders.It has been demonstrated that the composition of an individual's gut microbiome plays a significant part in determining that person's risk of developing depression.According to the hypothesis known as the gut-brain axis,there may be a connection between the intestinal microbial system and the brain.In recent years,it has been common practice to treat disorders by concentrating on the bacteria that are found in the digestive tract(for instance,by making use of probiotics)and incorporating the gut-brain axis mechanism.Our research revealed a remarkable association between the composition of the bacteria in the stomach and the incidence of depression.Alterations in the structure of the microbiota system in the gut could possibly have direct and special impacts on the rise in the prevalence of depression.This study investigated the mechanisms underlying the two-way communication in the gut-brain axis,including the current techniques of relieving symptoms and antidepressant medicines that are related to gut microbiota.An increase in the amount of research into the medical potential of probiotics has led to a rapid expansion of the field of probiotics over the past few decades.Numerous preclinical and clinical studies have established that the therapeutic effects of probiotics-mediated microbiota remodeling near the microbiota-gut-brain axis(MGBA)are present.These studies were conducted near one another.However,the potential effects of probiotics on numerous mental illnesses,which have been proved in vivo and in vitro research,have set the ground for the translation of preclinical models to humans,which is still in its infancy.