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.

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.

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.

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.

Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential.

“Sentinel or accomplice”:gut microbiota and microglia crosstalk in disorders of gut-brain interaction

Abnormal brain-gut interaction is considered the core pathological mechanism behind the disorders of gut-brain interaction(DGBI),in which the intestinal microbiota plays an important role.Microglia are the“sentinels”of the central nervous system(CNS),which participate in tissue damage caused by traumatic brain injury,resist central infection and participate in neurogenesis,and are involved in the occurrence of various neurological diseases.With in-depth research on DGBI,we could find an interaction between the intestinal microbiota and microglia and that they are jointly involved in the occurrence of DGBI,especially in individuals with comorbidities of mental disorders,such as irritable bowel syndrome(IBS).This bidirectional regulation of microbiota and microglia provides a new direction for the treatment of DGBI.In this review,we focus on the role and underlying mechanism of the interaction between gut microbiota and microglia in DGBI,especially IBS,and the corresponding clinical application prospects and highlight its potential to treat DGBI in individuals with psychiatric comorbidities.

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.

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 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.

基于肠道微生物菌群探讨针灸治疗肠易激综合征的效应机制

肠易激综合征是功能性胃肠病中最常见的一种,其病理生理机制非常复杂。近年来,肠道菌群在肠易激综合征相关研究中发挥了重要作用,肠道微生态失衡、菌群组成及多样性改变、有益菌减少而有害菌增加导致了疾病发生发展,以肠道菌群为导向的治疗手段也逐渐增多。同时,由于药物干预未能取得满意的疗效,在寻求替代疗法的过程中,针灸因其应用广泛、不良反应少而备受关注。相关研究表明针灸可以通过影响肠道菌群来调节肠道功能,改善肠易激综合征的症状。因此,本研究旨在论述肠道菌群与肠易激综合征的关系,并从调节肠道菌群的角度探讨针灸治疗肠易激综合征的效应机制。

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.

脑肠同调论针刺治疗急性脑梗死血清代谢组学研究

目的 分析脑肠同调论针刺治疗急性脑梗死的血清代谢组学的影响。方法 纳入2018年3月—2022年12月医院收治的急性脑梗死患者126例作为研究对象,随机数字表法分为两组,对照组63例采用常规疗法,观察组63例在此基础上采用脑肠同调论针刺治疗,对比两组治疗效果、神经功能,炎症因子水平以及对血清代谢组学的影响。结果 观察组总有效率为96.83%(61/63),远高于对照组的80.96%(57/63),神经功能缺损评分(NIHSS)评分低于对照组(P<0.05);治疗后观察组白介素-17(Interleukin-17,IL-17)、超敏C反应蛋白(hypersensitive C-reactive protein, hs-CRP)、血浆氧化三甲胺(trimethylamine oxide, TMAO)水平均低于对照组(P<0.05);治疗后观察组苯丙氨酸、溶血卵磷脂、焦谷氨酸水平低于对照组(P<0.05)。结论 脑肠同调论针刺治疗急性脑梗死效果明确,可减轻患者炎症反应,调节其肠道菌群代谢产物水平及氨基酸、磷脂代谢障碍等,使紊乱的代谢趋于正常,以达促进神经功能恢复,改善患者预后的目的,有较高应用价值。

适宜运动与过度训练调控肠道功能和肠-脑轴的作用机制

对运动介导肠道与大脑联络的相关文献进行综述,分析适宜运动与过度训练对肠道功能和肠-脑轴之间神经传导及生物信号分子的影响,以揭示其作用机制。发现:肠道与大脑之间关系密切,肠-脑轴之间的双向神经联系和相关生物信号分子是实现肠道与大脑之间对话的媒介。运动可通过调控肠道与大脑之间的神经联系和相关生物分子影响肠-脑轴,介导肠道与大脑的健康及神经、精神疾病的转归。肠道微生物是实现肠-脑轴之间信息沟通的重要参与者,运动对肠道功能与肠-脑轴的调节可通过调控肠道微生态,及其介导的神经传导途径和生物信号分子的变化发挥终端效应,进而影响高级神经功能。不同强度的运动对肠道微生态及肠-脑轴的调节效应差异颇大,适宜运动和过度训练引起的干预结果截然不同。

运脾柔肝方治疗便秘型肠易激综合征疗效观察及基于rs-fMRI脑区活动水平变化的研究

目的:观察运脾柔肝方治疗肝郁气滞型便秘型肠易激综合征(IBS-C)的临床疗效,运用静息态功能性磁共振(rs-fMRI)观察IBS-C患者的脑区活动水平变化。方法:选取我院门诊43例IBS-C患者,评价运脾柔肝方的临床疗效。选取20例健康受试者,观察IBS-C患者及健康受试者脑区活动水平差异。进行焦虑、抑郁评估,观察伴与不伴焦虑抑郁状态的患者脑区活动水平的差异。观察IBS-C患者治疗前后脑区活动水平差异。结果:治疗组与对照组治疗均有效(P>0.05)。治疗组患者经治疗后SAS和SDS评分均降低(P<0.05)。对照组患者经治疗后SAS评分降低(P<0.05)。静息状态下,IBS-C组患者左舌回的脑区活动水平升高,左额下回、右额中回的脑区活动水平降低(P<0.05)。伴焦虑抑郁情绪的IBS-C患者右额下回的脑区活动水平较不伴有焦虑抑郁情绪的患者升高(P<0.05)。治疗后IBS-C患者左顶叶中央后回、左侧距状裂周围皮层的脑区活动水平降低,小脑的脑区活动水平升高(P<0.05)。结论:运脾柔肝方可有效缓解IBS-C患者的临床症状,改善焦虑、抑郁情绪。在静息状态下,IBS-C患者大脑的特定区域活动异常,说明大脑的某些特定区域和相应网络的自发神经元活动的变化可能与IBS-C的病理生理密切相关。

梅花草提取物调节肠道菌群抑制原位脑胶质瘤模型的作用机制研究

目的探讨脑胶质瘤发生过程中梅花草对原位荷瘤鼠肠道菌群的影响。方法4周龄Balb/c雌性裸鼠颅内种植U87-MG或者RFP-U87-MG脑胶质瘤,前者用于肠道菌群检测(每组6只,分为2组),后者用于活体荧光成像评价脑胶质瘤的生长状态(每组3只,分为2组)。梅花草提取物经灌胃(25 mg/kg)隔天给药连续10次(植入后第6天至第24天),对照组为1×PBS。RFP-U87-MG模型鼠在第14天和第24天进行活体荧光成像观察肿瘤生长状态,同时进行裸鼠称量,并在第25天对裸鼠实施安乐死后,剥离脑组织和肿瘤,分别进行称重和组织的HE染色;而种植U87-MG的模型鼠,每3天称重,第25天实行安乐死收集结肠内新鲜粪便样本,以Illumina高通量测序技术分析肠道菌群,进行生物信息学挖掘潜在梅花草治疗相关的特征菌群。结果活体荧光成像和肿瘤病灶称重均提示梅花草提取物显著抑制原位脑肿瘤的恶性增殖,HE染色显示梅花草组肿瘤细胞数量减少、核浆比趋于正常,核异型性降低。经高通量测序发现梅花草提取物干预后并未影响荷瘤鼠肠道菌群的α多样性,而是影响特征菌群的丰度,其中梅花草提取物治疗后可以显著提高Muribaculum intestinale、Bacteroides faecichinchillae、Klebsiella oxytoca的菌种丰度,降低Lachnospiraceae bacterium A4和Helicobacter japonicus的丰度。结论梅花草提取物在显著抑制原位脑胶质瘤恶性增殖的同时,影响肠道菌群的丰度,其中特征菌群如Muribaculum intestinale、Bacteroides faecichinchillae等丰度增加,可能作为潜在益生菌参与脑肿瘤的机制调控。

利用孟德尔随机化分析日间过度思睡人群肠道菌群特点

目的探讨日间过度思睡(excessive daytime sleepiness,EDS)人群的肠道菌群变化特点。方法利用全基因组关联分析(genome-wide association study,GWAS)数据进行两样本孟德尔随机化分析,将肠道菌群作为暴露因素,EDS作为结局因素,以单核苷酸多态性(single nucleotidepolymorphism,SNP)作为工具变量,使用多种方法筛查EDS的潜在致病肠道微生物。通过使用不同的敏感度分析,确保孟德尔随机化分析结果的稳健性。结果综合多重分析结果,发现丁酸单胞菌、消化球菌、嗜胆菌、厌氧菌、瘤胃球菌和粪球菌在EDS人群中的丰度相对较高,而颤螺旋菌和脱硫弧菌的丰度相对较低。结论EDS人群存在肠道菌群失调,通过改变饮食结构、使用益生菌等措施调整肠道菌群结构是否可改善EDS有待于今后进一步研究证实。

Microbial phenolic metabolites are associated with better frontal lobe cognition

With increasing life expectancy,neurodegenerative diseases have become one of the leading causes of illhealth in the elderly.Preventive strategies include following healthy diets,such as the Mediterranean diet,which is particularly rich in polyphenols,bioactive compounds with neuroprotective properties.The aim of this study was to assess the association of microbial phenolic metabolites(MPM)with cognition.This cross-sectional analysis was performed with 200 participants of the PREDIMED trial(Barcelona-Clinic recruitment center).A novel method based on liquid chromatography coupled to mass spectrometry was used to identify urinary MPM(protocatechuic acid,enterodiol glucuronide,enterolactone glucuronide,urolithin B glucuronide,and vanillic acid glucuronide),and cognitive function was evaluated with neuropsychological tests.Multivariable-adjusted ordinary least squares regression was used to assess the associations between cognitive function and MPM,and a score was calculated as the weighted sum of MPM.A higher MPM score was associated with better frontal lobe function.Among individual metabolites,vanillic acid glucuronide was correlated with frontal cognitive performance.Participants with higher concentrations of vanillic acid glucuronide and urolithin B glucuronide obtained better scores in the Color Trail Test part 2.A higher score for urinary multiMPM was associated with better frontal cognitive performance in an older Mediterranean population.