黏膜免疫系统对肠-肺轴影响的研究进展

免疫系统是人体的重要防线,其功能强弱可由人体的患病和病愈状态反映。黏膜免疫在局部免疫、共同免疫以及防御外界有害微生物侵入机体过程中发挥了重要作用。呼吸道和胃肠道均具有黏膜免疫系统,二者可通过共同黏膜免疫相联系。近年来肠-肺轴的研究热度逐渐升高,而“肠-肺轴”的观点与中医学重要内容“肺与大肠相表里”不谋而合,可认为是此学说的现代发展。本文从黏膜免疫、肠-肺菌群层面总结了肠-肺轴的联系,以期阐明肺病肠治的科学依据。     

肠道-器官轴的研究进展

肠道通过神经、免疫、内分泌通路与多个器官相互作用,这种作用关系被称为肠道-器官轴。肠道微生物在肠道-器官轴中发挥了重要作用。基于这一理论,我们可以通过靶向肠道-器官轴来治疗肠道和多种相关器官的疾病。本文总结了肠-脑轴、肠-肝轴、肠-肺轴、肠-心轴、肠-皮轴、肠-脂肪轴的研究进展。     

短链脂肪酸:肠-器官轴调控疾病的信号使者

肠道菌群是一个复杂而动态的系统,对机体的健康至关重要。它作为机体的“第二基因组”,通过调节肠道神经、胃肠激素、肠屏障、肠道免疫和代谢与宿主重要脏器建立通讯轴,影响宿主的多种生理功能。短链脂肪酸作为肠道菌群的重要代谢产物,在机体的免疫、代谢、内分泌及信号传导等方面都有重要作用,是肠-器官轴上的重要通讯物质。本文总结了肠-肝/脑/肾/肺轴与疾病的互作关系,并重点探讨了短链脂肪酸在这种互作关系中的作用及机制,为相关疾病的治疗提供新思路。     

基于网络药理学探讨乌梅“敛肺涩肠”功效的作用机制

目的：基于网络药理学方法探讨乌梅“敛肺涩肠”功效的作用机制。方法：依托TCMSP数据库，结合文献查阅，收集乌梅相关成分，利用SIB和TCMSP平台预测成分靶点。联合GeneCards、CTD、TTD和Drugbank数据库检索“腹泻”和“哮喘”的靶点。将成分-靶点和疾病-靶点作交集得到乌梅“敛肺涩肠”的潜在靶点。利用Cytoscape 3.7.0软件构建成分-靶点网络。结果：从乌梅中筛选出29个化合物，苦杏仁苷和槲皮苷可能是“敛肺涩肠”的关键成分；23个乌梅“敛肺涩肠”的潜在靶点50%以上在肺和结肠中显著表达；基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路分析得到142个GO条目和43条KEGG通路。结论：本研究揭示了乌梅通过多成分、多靶点和多通路发挥“敛肺涩肠”功效的内涵，为乌梅的临床应用提供科学依据。     

肠道菌群与神经退行性疾病相关性研究进展

人体肠道中微生物群落富集,菌群失调与宿主的健康及疾病的发生发展密切相关。有研究发现,肠道菌群主要通过“脑-肠轴”这一双向通信路径,对大脑功能产生一定影响。但其具体机制尚不明确。因此,本文就肠道菌群、“脑-肠轴”以及肠道菌群与神经退行性疾病之间可能存在的相关性加以阐述分析,以期为此类疾病的临床防治提供新的治疗靶点。     

肠道菌群在新冠肺炎中的作用及以肠道菌群为靶标的治疗

由严重急性呼吸系统综合征2型冠状病毒(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)目前在全球范围蔓延严重。新冠肺炎患者除了通常会出现发热和严重的呼吸系统症状,部分患者会出现腹泻、呕吐、恶心、厌食和腹痛等胃肠道症状,目前仍缺乏有效的抗病毒药物用于该病的治疗。中医经典理论“肺与大肠相表里”与现代医学的“肺-肠轴”相吻合,提示调节肠道菌群稳态的相关产品可能有助于控制这种病毒感染。文章就肠道菌群与呼吸道病毒性疾病的关系、利用益生菌和营养疗法平衡肠道菌群、调节免疫应答从而对COVID-19患者进行治疗等问题进行综述,为治疗COVID-19寻找替代途径。     

肠道微生物参与偏头痛发病机制的研究进展

偏头痛是临床上常见的一种神经紊乱性疾病,由于其病因复杂,发病机制尚未完全阐明,目前对于偏头痛的防治还处于不断探索阶段。近期研究提出的“微生物群-肠-脑轴”理论为偏头痛发病机制的研究提供了新的可能,其认为肠道微生物通过“肠-脑”轴参与中枢系统的调控可能会导致神经系统疾病的发生。因此,本文通过综述国内外相关文献报道,结合偏头痛的病因及发病机制,详述肠道微生物与神经系统疾病之间的关系,阐明肠道微生物参与偏头痛发生发展的可能机制,并对后续研究进行展望,以期为偏头痛发病机制研究及治疗新药物开发奠定理论基础。     

肝肠轴相关机制研究进展

1998年马歇尔提出了“肠-肝轴”的概念,从此肝脏疾病的发生与肠黏膜屏障的作用就逐渐受到关注。目前的研究认为,如果肠道黏膜屏障功能受损,致使肠道黏膜的通透性发生改变,从而导致肠道内的细菌及其产物（如内毒素等）,通过血液循环（通常是门静脉系统）进入肝脏,引起肝脏固有免疫系统如Kupffer细胞（kupffer cell,KC）等被肠道产物激活,释放一系列炎性因子,这些炎性因子可进一步造成肠道黏膜及远隔器官损伤。因此,保护肠黏膜屏障可能是治疗肝脏疾病的开创性治疗方法和辅助治疗方法。进一步认识肝肠轴相互作用的机制可为临床上治疗肝脏疾病提供新的思路。本文就肝肠轴的相关机制及研究该机制的重要性作一综述。     

炎症信号在脑-肠轴中的传递及药物干预机制研究进展

中枢神经系统疾病与某些外周疾病具有共生的特点,由＂脑-肠轴＂介导的炎症信号在外周和中枢间的传递被认为是联系中枢系统疾病与外周炎症的重要途径,这一机制对于全面认识中枢神经系统疾病的发病机制以及相关疾病的预防和治疗具有重要意义。本文就＂脑-肠轴＂介导的炎症信号传递对神经精神疾病,尤其是抑郁症的影响及其机制进行了综述,并探讨了干预＂脑-肠轴＂炎症信号对于中枢神经系统疾病的预防和治疗的潜在前景。     

牙周炎与肝脏疾病的关系研究进展

作为消化道的起点,口腔与肠道和肝脏有着天然的联系。口腔疾病也与肝脏疾病密切相关,牙周炎是最常见的口腔疾病,其牙周细菌病变往往通过直接的解剖学侵袭和口-肠-肝轴影响肝病的预后和进展,牙周细菌还可通过门静脉循环的受损肠上皮细胞影响肝脏。该文对牙周炎、口-肠-肝轴和肝脏疾病进行了系统综述。     

Gut–Kidney Axis Investigations in Animal Models of Chronic Kidney Disease

Chronic kidney disease (CKD) is an incurable disease in which renal function gradually declines, resulting in no noticeable symptoms during the early stages and a life-threatening disorder in the latest stage. The changes that accompany renal failure are likely to influence the gut microbiota, or the ecosystem of micro-organisms resident in the intestine. Altered gut microbiota can display metabolic changes and become harmful to the host. To study the gut–kidney axis in vivo, animal models should ideally reproduce the disorders affecting both the host and the gut microbiota. Murine models of CKD, but not dog, manifest slowed gut transit, similarly to patient. Animal models of CKD also reproduce altered intestinal barrier function, as well as the resulting leaky gut syndrome and bacterial translocation. CKD animal models replicate metabolic but not compositional changes in the gut microbiota. Researchers investigating the gut–kidney axis should pay attention to the selection of the animal model (disease induction method, species) and the setting of the experimental design (control group, sterilization method, individually ventilated cages) that have been shown to influence gut microbiota.     

A Healthy Gut for a Healthy Brain: Preclinical,Clinical and Regulatory Aspects

A large body of research has shown the presence of a complex pathway of communications between the gut and the brain. It is now recognized that, through this pathway, the microbiota can influence brain homeostasis and plasticity under normal and pathological conditions.This review aims at providing an overview of preclinical and clinical pieces of evidence supporting the possible role of gut-brain axis modulation in physiological aging, in a neurodevelopmental disorder, the autism spectrum disorders and in a substance abuse disorder, the alcohol addiction.Since the normalization of gut flora can prevent changes in the behavior, we postulate that the gut-brain axis might represent a possible target for pharmacological and dietary strategies aimed at improving not only intestinal but also mental health. The present review also reports some regulatory considerations regarding the use of probiotics, illustrating the most debated issues about the possibility of considering probiotics not only as a food supplement but also as a “full” medicinal product.     

Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications

The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota have also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.     

Dysbiosis-Related Advanced Glycation Endproducts and Trimethylamine N-Oxide in Chronic Kidney Disease

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs.     

药物基于“肠-脑”通路的研究进展

肠道菌群是由诸多共生及致病微生物组成的复杂而动态的群落,并与宿主紧密合作.近年来,越来越多的证据支持“肠-脑”轴理论,肠道菌群与神经精神疾病之间的联系逐步被发现.由于神经精神疾病治疗药物大多经口服后进入肠道,使得其与肠道菌群可能产生更广泛的相互作用.多项研究表明该类药物可改变肠道菌群的组成和功能,同时肠道菌群也会参与药...     

Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and in...     

Neuroendocrinology of gastric H+ and duodenal HCO3- secretion: the role of brain-gut axis

Gastric H+ and duodenal HCO3- secretions are precisely regulated by neuro-hormonal mechanisms at central and peripheral levels to match the rate of these secretions with the type of stimulation of sensory receptors in the head area (sight, smell, taste, etc.) and in the gastro-intestinal system. Two-way communication pathways operate between the brain and the gut, each comprising afferent fibers signaling sensory information from the gut to the brain and efferent fibers transmitting signals in opposite direction. Short intramural and long extramural reflexes are triggered as well as various gut hormones are released by feeding that "cooperate" with the "brain-gut axis" in the alteration of exocrine and endocrine gastro-duodenal secretion, motility and blood circulation. The malfunction of gastric or duodenal secretory mechanisms may lead to disturbances of gastric H+-pepsin or duodenal mucus-HCO3- secretion and to gastro-duodenal disorders and diseases. This review presents recent advances in pathophysiological mechanisms underlying gastro-duodenal secretory disorders.     

Modulating Gut Microbiota: An Emerging Approach in the Prevention and Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is a progressive neuromuscular disorder characterized by demyelination of neurons of the central nervous system (CNS). The pathogenesis of the disorder is described as an autoimmune attack targeting the myelin sheath of nerve cell axons in the CNS. Available treatments only reduce the risk of relapse, prolonging the remissions of neurological symptoms and halt the progression of the disorder. Among the new ways of targeting neurological disorders, including MS, there is modulation of gut microbiota since the link between gut microbiota has been rethought within the term gut-brain axis. Gut microbiota is known to help the body with essential functions such as vitamin production and positive regulation of immune, inflammatory, and metabolic pathways. High consumption of saturated fatty acids, gluten, salt, alcohol, artificial sweeteners, or antibiotics is the responsible factor for causing gut dysbiosis. The latter can lead to dysregulation of immune and inflammatory pathways, which eventually results in leaky gut syndrome, systemic inflammation, autoimmune reactions, and increased susceptibility to infections. In modern medicine, scientists have mostly focused on the modulation of gut microbiota in the development of novel and effective therapeutic strategies for numerous disorders, with probiotics and prebiotics being the most widely studied in this regard. Several pieces of evidence from preclinical and clinical studies have supported the positive impact of probiotic and/or prebiotic intake on gut microbiota and MS. This review aims to link gut dysbiosis with the development/progression of MS, and the potential of modulation of gut microbiota in the therapeutics of the disease.     

Dopamine: a stress modulator in the brain and gut.

1. Central dopamine (DA) exhibits large and rapid responses to stress challenge, particularly in the mesolimbic DA tract and, to a lesser degree, in the mesocortical tract. 2. Over the last few years, there has emerged an increasing role for peripheral DA, especially gastrointestinal DA, as a modulator of gastroduodenal injury consequent to stress exposure. 3. Evidence has accumulated which strongly supports a role for DA as an endogenous gastroprotective element and it appears that the dopaminergic "brain-gut axis" is a critical determinant of gastroduodenal mucosal integrity in the stress-challenged gut.