Correlation between the neuroendocrine axis,microbial species,inflammatory response,and gastrointestinal symptoms in irritable bowel syndrome

BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Elaidic acid-induced intestinal barrier damage led to gut-liver axis derangement and triggered NLRP3 inflammasome in the liver of SD rats

Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.

Intestinal flora and depressive disorders:exploration and prospect of microbial-gut-brain axis

This paper examines the correlation between depressive disorders and intestinal flora.Depression is a common affective disorder characterized by low mood,loss of interest,anhedonia,high incidence,high recurrence rate,high disability rate,and high medical costs.The incidence and harmfulness of depressive disorder are gradually increasing,and its etiology is complex and diverse,among which the abnormal intestinal flora is considered to be one of the causes of depressive disorder.This article reviews the results of several studies that found intestinal flora imbalance in depressed patients,including changes in the type and quantity of flora and changes in metabolic pathways.In addition,antibiotic and probiotic treatments have also been shown to be effective in alleviating depressive symptoms,further indicating the importance of intestinal flora disturbances in the pathogenesis of depression.We also explored the relationship between intestinal flora and the pathogenesis of depressive disorders.Through neuro-immuno-endo-crine-metabolic pathways,intestinal flora can affect the function of the central nervous system,cause changes in the host’s mental behavior,and lead to or aggravate depressive symptoms.Overall,this study not only found differences in the intestinal flora of patients with depressive disorders but also revealed the potential role of intestinal flora in the pathogenesis.Importantly,this provides a new theoretical basis for further clarifying the pathogenesis of depressive disorders and formulating diagnosis and treatment strategies.

Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

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.

Thinking on the Treatment of Lung Cancer by Regulating Lung-Intestinal Axis Microecology by Traditional Chinese Medicine

The intestinal microecological disorder is closely related to the occurrence and development of lung cancer and the treatment response.This paper starts with the relationship between the lungintestinal axis,to discuss the possibility of TCM regulating the target of intestinal microecological treatment of lung cancer,so as to provide new research ideas for TCM treatment of lung cancer.

Research Progress in Intestinal Flora and Hepatocellular Carcinoma

Intestinal flora are involved in environmental homeostasis and the development of many diseases within the human body. The liver, as one of the most important digestive organs in human beings, communicates with the intestinal flora and their metabolites in the intestine through the biliary system, the hepatic portal system, and the corpuscular circulation, an interrelated system known as the intestinal-hepatic axis. Hepatocellular carcinoma is the most common malignant tumor of the liver and one of the leading causes of cancer-related deaths worldwide. There is increasing evidence that intestinal flora plays an important role in the evolution of hepatocellular carcinoma. Besides, intestinal flora has great potential in the treatment of liver cancer. On this basis, this paper summarizes the relevant studies on the role of intestinal flora in the development of hepatocellular carcinoma and discusses its potential value in the treatment of hepatocellular carcinoma.

Intestinal barrier dysfunction as a key driver of severe COVID-19

The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with intestinal immune cells and with epithelial and endothelial cells,forming a multi-layered barrier that enables the efficient absorption of nutrients without an excessive influx of pathogens.Despite being a lung-centered disease,severe coronavirus disease 2019(COVID-19)affects multiple systems,including the gastrointestinal tract and the pertinent gut barrier function.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can inflict either direct cytopathic injury to intestinal epithelial and endothelial cells or indirect immune-mediated damage.Alternatively,SARS-CoV-2 undermines the structural integrity of the barrier by modifying the expression of tight junction proteins.In addition,SARS-CoV-2 induces profound alterations to the intestinal microflora at phylogenetic and metabolomic levels(dysbiosis)that are accompanied by disruption of local immune responses.The ensuing dysregu-lation of the gut-lung axis impairs the ability of the respiratory immune system to elicit robust and timely responses to restrict viral infection.The intestinal vasculature is vulnerable to SARS-CoV-2-induced endothelial injury,which simultaneously triggers the activation of the innate immune and coagulation systems,a condition referred to as“immunothrombosis”that drives severe thrombotic complications.Finally,increased intestinal permeability allows an aberrant dissemination of bacteria,fungi,and endotoxin into the systemic circulation and contributes,to a certain degree,to the over-exuberant immune responses and hyper-inflammation that dictate the severe form of COVID-19.In this review,we aim to elucidate SARS-CoV-2-mediated effects on gut barrier homeostasis and their implications on the progression of the disease.

A theoretical deduction for the location of neutral axis in intestine at unloaded configuration

The function of Gastrointestinal tract including intestine is to a large degree mechanical.The mechanical properties of the intestinal wall,and the tonic (sustained) and/or phasic(short-

Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

Gut-liver axis signaling in portal hypertension

Portal hypertension(PHT)in advanced chronic liver disease(ACLD)results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition(structural component)and intrahepatic vasoconstriction(functional component).PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding.Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns(PAMPs)that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways.Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability:The intestinal barrier function is affected by impaired microcirculation,neoangiogenesis,and abnormal vascular and mucosal permeability.The close bidirectional relationship between the gut and the liver has been termed“gut-liver axis”.Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function,intestinal barrier integrity,as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects.The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments,however,further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed.In this review,we summarize the clinical impact of PHT on the course of liver disease,discuss the underlying pathophysiological link of PHT to gut-liver axis signaling,and provide insight into molecular mechanisms that may represent novel therapeutic targets.

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.

Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis

BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth(SIBO)are commonly observed in patients with cirrhosis.Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis,dysbiosis and SIBO were always studied separately.AIM To study the relationship of gut dysbiosis and SIBO in cirrhosis.METHODS This observational study included 47 in-patients with cirrhosis.Stool microbiome was assessed using 16 S r RNA gene sequencing.SIBO was assessed using the lactulose hydrogen breath test.RESULTS SIBO was found in 24/47(51.1%)patients.Patients with SIBO had a higher abundance of Firmicutes(P=0.017)and Fusobacteria(P=0.011),and a lower abundance of Bacteroidetes(P=0.013)than patients without SIBO.This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia(P=0.020)of the Lachnospiraceae family(P=0.047),while the abundance of other major families of this phylum[Ruminococcaceae(P=0.856),Peptostreptococcaceae(P=0.066),Clostridiaceae(P=0.463),Eubacteriaceae(P=0.463),Lactobacillaceae(P=0.413),and Veillonellaceae(P=0.632)]did not differ significantly between the patients with and without SIBO.Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum[Bacteroidaceae(P=0.014),Porphyromonadaceae(P=0.002),and Rikenellaceae(P=0.047)],with the exception of Prevotellaceae(P=0.941).There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis[Proteobacteria(P=0.790),Bacilli(P=0.573),Enterobacteriaceae(P=0.632),Streptococcaceae(P=0.170),Staphylococcaceae(P=0.450),and Enterococcaceae(P=0.873)]between patients with and without SIBO.CONCLUSION Despite the differences observed in the gut microbiome between patients with and without SIBO,gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.

Partially hydrolyzed guar gum attenuates non-alcoholic fatty liver disease in mice through the gut-liver axis

BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.

Intestinal microbiota in the treatment of metabolically associated fatty liver disease

Metabolically associated fatty liver disease (MAFLD) is a common cause ofchronic liver disease, the hepatic manifestation of metabolic syndrome. Despitethe increasing incidence of MAFLD, no effective treatment is available. Recentresearch indicates a link between the intestinal microbiota and liver diseases suchas MAFLD. The composition and characteristics of the intestinal microbiota andtherapeutic perspectives of MAFLD are reviewed in the current study. Animbalance in the intestinal microbiota increases intestinal permeability andexposure of the liver to adipokines. Furthermore, we focused on reviewing thelatest "gut-liver axis" targeted therapy.

Intestinal microbiota participates in nonalcoholic fatty liver disease progression by affecting intestinal homeostasis

Nonalcoholic fatty liver disease(NAFLD)is a chronic liver disease with a pathogenesis that has not been fully elucidated.With the development of the theory of the gut-liver axis and the deepening of related research,the role of the intestinal tract in the pathogenesis of NAFLD has been investigated more.Intestinal microbiota,intestinal metabolites,and intestinal epithelial and immunebased barriers constitute the intestinal environment,which uses crosstalk to maintain the homeostasis of the intestinal environment.This paper reviews the progress in the study of intestinal microbiota,intestinal environment,and NAFLD and suggests that repair of intestinal functional balance may be a new idea for early prevention and intervention of NAFLD.

L.reuteri ZJ617 inhibits inflammatory and autophagy signaling pathways in gut-liver axis in piglet induced by lipopolysaccharide

Background:This study investigated the protective effects of L.reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory,autophagy,and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide(LPS).Methods:Duroc×Landrace×Large White piglets were assigned to 3 groups(n=6/group):control(CON)and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection(i.p.)of physiological saline or LPS(25μg/kg body weight),respectively,while the ZJ617+LPS group was orally inoculated with ZJ617 for 2 weeks before i.p.of LPS.Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity,serum biochemical parameters,inflammatory signaling involved in molecular and liver injury pathways.Results:Compared with controls,LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK,phosphorylated-ERK and JNK protein levels and decreased IκBαprotein expression,while serum LPS,TNF-α,and IL-6 concentrations(P<0.05)increased.ZJ617 pretreatment significantly countered the effects induced by LPS alone,with the exception of p-JNK protein levels.Compared with controls,LPS stimulation significantly increased LC3,Atg5,and Beclin-1 protein expression(P<0.05)but decreased ZO-1,claudin-3,and occludin protein expression(P<0.05)and increased serum DAO and D-xylose levels,effects that were all countered by ZJ617 pretreatment.LPS induced significantly higher hepatic LC3,Atg5,Beclin-1,SOD-2,and Bax protein expression(P<0.05)and lower hepatic total bile acid(TBA)levels(P<0.05)compared with controls.ZJ617 pretreatment significantly decreased hepatic Beclin-1,SOD2,and Bax protein expression(P<0.05)and showed a tendency to decrease hepatic TBA(P=0.0743)induced by LPS treatment.Pretreatment of ZJ617 before LPS injection induced the production of 5 significant metabolites in the intestinal contents:capric acid,isoleucine 1TMS,glycerol-1-phosphate byproduct,linoleic acid,alanine-alanine(P<0.05).Conclusions:These results demonstrated that ZJ617 pretreatment alleviated LPS-induced intestinal tight junction protein destruction,and intestinal and hepatic inflammatory and autophagy signal activation in the piglets.

基于肠-肝轴探讨清肝降脂方对代谢相关脂肪性肝病大鼠肠道屏障的作用研究

目的基于肠-肝轴理论探讨清肝降脂方对高脂饲料诱导的代谢相关脂肪性肝病(MAFLD)大鼠肠道屏障的作用。方法60只SPF级雄性SD大鼠,随机抽取10只作为正常组,余下作为高脂饮食组,给予高脂饲料喂养8周。造模成功后,将高脂饮食组大鼠随机分为模型组和中药低剂量组、中剂量组、高剂量组及水林佳组。观察各组大鼠肝脏及回肠末端组织病理变化、血清生化学及血清内毒素水平,回肠组织中紧密连接蛋白ZO-1、Occludin表达情况。结果与正常组比较,模型组大鼠肝脏和回肠组织可见明显病理损伤,血清ALT、TC、TG、LDL-C及血清LPS水平表达量均明显增高,均具有统计学意义(P<0.05),回肠组织中ZO-1、Occludin蛋白阳性表达降低(P<0.05)。与模型组比较,水林佳组和中药高、中剂量均能明显降低ALT、TC、TG水平,降低LDL-C含量(P<0.05)。水林佳及中药组大鼠血清LPS水平均明显低于模型组(P<0.05),水林佳组以及中药高、中剂量组ZO-1、Occludin蛋白阳性表达增多,中药低剂量组蛋白表达略增加。结论清肝降脂方可以调节大鼠脂质代谢,修复肠道紧密连接,维持正常肠道黏膜屏障功能,阻止肠内炎性因子、内毒素等进入肝脏,提示清肝降脂方治疗MAFLD作用机制可能与调节肠-肝轴、改善肠道免疫屏障有关。

孤独症谱系障碍与肠道菌群的相关性的研究进展

孤独症谱系障碍(ASD)是一组具有高度遗传异质性的神经发育障碍性疾病。除了神经症状,许多ASD儿童常合并胃肠道症状。越来越多的证据表明,ASD儿童肠道菌群的组成发生显著变化,异常的肠道菌群可能通过微生物-肠-脑轴参与ASD的发生和发展。目前,尚无有效的药物改善ASD的核心症状。本文针对肠道微生态菌群及其代谢产物与ASD之间的潜在关系,以及微生态疗法(益生菌、益生元、粪菌移植)在ASD中的应用价值展开综述,旨在为改善ASD儿童核心症状提供更多的参考。

基于“皮-肠轴”理论探讨肠道菌群与糖尿病溃疡的关系

糖尿病溃疡(dabetic ulcer)是糖尿病(diabetes mellitus)的严重并发症之一,具有迁延难愈、易感染、易导致截肢或脓毒症的特点[1]。据统计,2016年,全球糖尿病下肢并发症患者约1.31亿,其中250万患者因足部溃疡导致残疾而缩短生命[2]。糖尿病溃疡难愈原因复杂,涉及血管因素、神经因素、免疫因素及微生物因素,其中创面微生物的变化以及与不同细胞作用产生的免疫应答影响了创面的修复[3]。