短链脂肪酸在2型糖尿病发病机制中的作用

短链脂肪酸(SCFA)是由肠道菌群发酵膳食纤维产生的代谢产物,饮食结构变化通过改变肠道菌群结构与功能,影响SCFA的产生.近来研究发现,SCFA通过调节胃肠道激素分泌、胰岛素敏感性及糖、脂代谢,参与了2型糖尿病的发生、发展.对SCFA的深入研究,为阐明2型糖尿病发病机制及其预防和治疗提供了新的思路和靶点.     

短链脂肪酸与肠易激综合征关系的研究进展

肠易激综合征(irritable bowel syndrome, IBS)是一种发病机制尚未完全明确的功能性肠病.以不规则的腹痛、腹胀、排便习惯和粪便性状改变为主要临床表现.肠道菌群失调作为IBS的病理机制之一,在IBS发生发展中扮演着极其重要的角色.绝大多数的短链脂肪酸(short-chain fatty acids, SCFAs)是由肠道菌群和宿主饮食在结肠相互作用后产生的.作为肠道菌群的主要代谢产物之一, SCFAs在肠道中发挥着维护肠道屏障功能、免疫调节、抗炎、调节内脏敏感性等作用.近几年来,随着人们对于SCFAs关注度的增加,探讨SCFAs与IBS之间关系的研究越来越多.本文对近五年来SCFAs与IBS关系的研究进展进行总结.     

短链脂肪酸在炎症性肠病中的研究进展

炎症性肠病(IBD)是由遗传和环境因素共同驱动导致的肠道慢性炎症性疾病.肠道菌群发酵膳食纤维产生的短链脂肪酸(SCFAs)具有抗炎和维持肠道稳态的作用,肠道炎症和低纤维饮食均可导致产SCFAs细菌数量减少,进而影响肠道免疫和代谢调节.本文就SCFAs在IBD中的研究进展作一综述.     

短链脂肪酸在肠道中的生理作用

越来越多的证据显示,短链脂肪酸对肠道的能量供应、肠黏膜屏障的维持、肠道高敏感和肠道动力的调节、免疫调节及抗肿瘤效应等有重要作用。进一步明确短链脂肪酸的生理作用及其与肠道相关疾病的关联及其内在机制,对肠道疾病的预防与治疗有重要意义。该文就短链脂肪酸在肠道中的生理作用作一综述。     

短链脂肪酸及对结肠炎的治疗作用

短链脂肪酸是人类结肠中碳水化合物经微生物发酵后的主要产物,对肠道的作用包括促进回、结肠的运动,增加肠粘膜血流及氧的摄入,增加细胞增殖,防止上皮细胞和腺体萎缩,促进手术后组织修复,防止渗漏等。近年来的研究表明,应用短链脂肪酸可以改善转流性结肠炎,远段溃疡性结肠炎,袋囊炎,放射性结肠炎的临床症状,内镜和组织学表现。     

老年帕金森病与肠道菌群、短链脂肪酸和炎性因子相关性研究

目的 探讨老年PD与肠道菌群、短链脂肪酸和炎性因子的相关性.方法 通过16S rDNA基因实时荧光定量PCR检测PD病人和对照组人群粪样普拉梭菌(F.prausnitzii)、直肠真杆菌(E.rectale)、双歧杆菌(Bifidobacterium)、乳酸菌(Lactobacillis)水平;通过气相色谱法检测2组人...     

短链脂肪酸与心脏自主神经系统

短链脂肪酸是肠道菌群的重要代谢产物,主要包括丁酸盐、乙酸盐和丙酸盐,其对心脏自主神经系统具有重要的生理、病理调节作用。短链脂肪酸可通过肠-脑轴间接调节交感神经和副交感神经系统活性发挥心血管保护作用,亦可进入循环血液后直接作用于短链脂肪酸受体影响心脏自主神经功能。     

短链脂肪酸及对结肠炎的治疗作用

短链脂肪酸是人类结肠中碳水化合物经微生物发酵后的主要产物,对肠道的作用包括促进回、结肠的运动,增加肠粘膜血流及氧的摄入,增加细胞增殖,防止上皮细胞和腺体萎缩,促进手术后组织修复,防止渗漏等。近年来的研究表明,应用短链脂肪酸可以改善转流性结肠炎、远段溃疡性结肠炎、袋囊炎、放射性结肠炎的临床症状、内镜和组织学表现。     

短链脂肪酸在冠心病防治中的研究进展

短链脂肪酸(SCFA)可以预防及治疗冠心病的危险因素、抑制其发病机制及改善预后.可以通过补充SCFA或者增加膳食纤维、移植产SCFA的肠道菌群、适量减少盐的摄入以及服用一些中药来增加体内的SC-FA含量,防治冠心病.本文综述了SCFA在冠心病的危险因素、发病机制以及并发症中的研究进展,以期为SC-FA在冠心病防治中作用...     

肠道菌群通过短链脂肪酸参与过敏性哮喘发病的相关机制研究进展

过敏性哮喘是一种由多种细胞参与的,以可逆性气流受限和气道高反应性(AHR)为特点的气道慢性炎症性疾病.肠道菌群参与调节人体免疫反应,与哮喘的发病机制相关.短链脂肪酸(SCFAs)是肠道微生物群产生的一类信号分子,在多种疾病的发生、发展中发挥着重要作用.SCFAs可激活G蛋白耦联受体或ERK1/2信号通路,同时通过组蛋白...     

The emerging role of gut microbiota in cardiovascular diseases

There is mounting evidence which suggests the involvement of gut microbiota dysbiosis in the pathogenesis of various cardiovascular diseases (CVD) and associated risk states such as hypertension, type 2 diabetes, obesity and dyslipidaemia, atherosclerosis, heart failure and atrial fibrillation. The current review comprehensively summarizes the various pathogenetic mechanisms of dysbiosis in these conditions and discusses the key therapeutic implications. Further deeper understanding of the pathogenetic links between CVD and gut microbiota dysbiosis can aid in the development of novel microbiota-based targets for the management of CVDs.     

Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation

The presence of >100 trillion microorganisms (collectively called gut microbiota) in our large intestine is essential for the maintenance of health. The gut microbiota starts to develop before birth and matures within first three years of life. The Western diet and lifestyle have been implicated in causing an imbalance of gut microbial communities and their metabolites that consequence in disease states, such as obesity and asthma. With more than 13% of the world population currently living with obesity and one out of 10 children diagnosed with asthma, we explore here the recent developments in the biosynthesis and mode of action of the key metabolites in relation to these two chronic inflammatory conditions.     

G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment

Nonalcoholic fatty liver disease(NAFLD)is a broad-spectrum disease,ranging from simple hepatic steatosis to nonalcoholic steatohepatitis,which can progress to cirrhosis and liver cancer.Abnormal hepatic lipid accumulation is the major manifestation of this disease,and lipotoxicity promotes NAFLD progression.In addition,intermediate metabolites such as succinate can stimulate the activation of hepatic stellate cells to produce extracellular matrix proteins,resulting in progression of NAFLD to fibrosis and even cirrhosis.G protein-coupled receptors(GPCRs)have been shown to play essential roles in metabolic disorders,such as NAFLD and obesity,through their function as receptors for bile acids and free fatty acids.In addition,GPCRs link gut microbiota-mediated connections in a variety of diseases,such as intestinal diseases,hepatic steatosis,diabetes,and cardiovascular diseases.The latest findings show that gut microbiota-derived acetate contributes to liver lipogenesis by converting dietary fructose into hepatic acetyl-CoA and fatty acids.GPCR agonists,including peptides and natural products like docosahexaenoic acid,have been applied to investigate their role in liver diseases.Therapies such as probiotics and GPCR agonists may be applied to modulate GPCR function to ameliorate liver metabolism syndrome.This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment.Overall,understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD.     

Role of gut microbiota on intestinal barrier function in acute pancreatitis

Acute pancreatitis(AP) is a common gastrointestinal disorder. Approximately15%-20% of patients develop severe AP. Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage. A study showed that 59% of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability, leading to intestinal bacterial translocation, pancreatic tissue necrosis and infection, and the occurrence of multiple organ dysfunction syndrome. However, the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear. This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.     

Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition

AIM: To assess the effects of Sb on fecal flora and short-chain fatty acids (SCFA) in patients on long-term TEN. METHODS: Ten patients (3 females, 7 males, 59±5.5 years), on TEN for a median of 13 mo (1-125), and 15 healthy volunteers (4 females, 11 males, 32±2.0 years) received Sb (0.5 g bid PO) for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values (mean±SE) were compared using sign tests and ANOVA. RESULTS: Fecal butyrate levels were lower in patients (10.1±2.9 mmol/kg) than in controls (19.2±3.9, P= 0.02). Treatment with Sb increased total fecal SCFA levels in patients (150.2±27.2 vs 107.5±18.2 mmol/kg, P= 0.02) but not in controls (129.0±28.6 vs 113.0±15.2 mmol/kg, NS). At the end of treatment with Sb, patients had higher fecal butyrate (16.0±4.4 vs 10.1 [2.9] mmol/kg, P= 0.004). Total SCFAs remained high 9 d after treatment was discontinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls (2.4±2.3 vs 69.8±1.8, P= 0.003). There were no significant changes in the fecal flora of TEN patients. CONCLUSION: Sb-induced increase of fecal SCFA concentrations (especially butyrate) may explain the preventive effects of this yeast on TEN-induced diarrhea.     

New strain of Pediococcus pentosaceus alleviates ethanol-induced liver injury by modulating the gut microbiota and short-chain fatty acid metabolism

BACKGROUND Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease(ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective microbe-based therapy is lacking. Pediococcus pentosaceus(P. pentosaceus) CGMCC 7049 is a newly isolated strain of probiotic that has been shown to be resistant to ethanol and bile salts. However, further studies are needed to determine whether P. pentosaceus exerts a protective effect on ALD and to elucidate the potential mechanism.AIM To evaluate the protective effect of the probiotic P. pentosaceus on ethanol-induced liver injury in mice.METHODS A new ethanol-resistant strain of P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge model of experimental ALD was established to evaluate the protective effects. Twenty-eight C57BL/6 mice were randomly divided into three groups: The control group received a pairfed control diet and oral gavage with sterile phosphate buffered saline, the EtOH group received a ten-day Lieber-DeCarli diet containing 5% ethanol and oral gavage with phosphate buffered saline, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet but was treated with P. pentosaceus. One dose of isocaloric maltose dextrin or ethanol was administered by oral gavage on day 11, and the mice were sacrificed nine hours later. Blood and tissue samples(liver and gut) were harvested to evaluate gut barrier function and liver injury-related parameters. Fresh cecal contents were collected, gas chromatography–mass spectrometry was used to measure short-chain fatty acid(SCFA) concentrations, and the microbiota composition was analyzed using 16S rRNA gene sequencing.RESULTS The P. pentosaceus treatment improved ethanol-induced liver injury, with lower alanine aminotransferase, aspartate transaminase and triglyceride levels and decreased neutrophil infiltration. These changes were accompanied by decreased levels of endotoxin and inflammatory cytokines, including interleukin-5, tumor necrosis factor-α, granulocyte colony-stimulating factor, keratinocyte-derived protein chemokine, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Ethanol feeding resulted in intestinal dysbiosis and gut barrier disruption, increased relative abundance of potentially pathogenic Escherichia and Staphylococcus, and the depletion of SCFA-producing bacteria, such as Prevotella, Faecalibacterium, and Clostridium. In contrast, P. pentosaceus administration increased the microbial diversity, restored the relative abundance of Lactobacillus, Pediococcus, Prevotella, Clostridium and Akkermansia and increased propionic acid and butyric acid production by modifying SCFA-producing bacteria. Furthermore, the levels of the tight junction protein ZO-1, mucin proteins(mucin [MUC]-1, MUC-2 and MUC-4) and the antimicrobial peptide Reg3β were increased after probiotic supplementation.CONCLUSION Based on these results, the new strain of P. pentosaceus alleviated ethanol-induced liver injury by reversing gut microbiota dysbiosis, regulating intestinal SCFA metabolism, improving intestinal barrier function, and reducing circulating levels of endotoxin and proinflammatory cytokines and chemokines. Thus, this strain is a potential probiotic treatment for ALD.     

Prebiotic UG1601 mitigates constipation-related events in association with gut microbiota: A randomized placebo-controlled intervention study

BACKGROUND Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial. Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation. Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids(SCFAs), which can help relieve constipation symptoms. The prebiotic UG1601 consists of inulin,lactitol, and aloe vera gel, which are known laxatives, but randomized, controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking.AIM To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation.METHODS Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk. All participants provided their fecal and blood samples at baseline and at the end of intervention.Gastrointestinal symptoms and stool frequency were evaluated. The concentrations of serum endotoxemia markers and fecal SCFAs were determined.The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated.RESULTS There were no significant differences in gastrointestinal symptoms between groups, although the prebiotic group showed greater symptom improvement.However, after prebiotic usage, serum cluster of differentiation(CD) 14 and lipopolysaccharide(LPS) concentrations were significantly decreased(CD14, P =0.012; LPS, P 0.001). The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group(P 0.001). Fecal SCFAs concentrations did not differ between groups, while the relative abundance of Roseburia hominis, a major butyrate producer, was significantly increased in the prebiotic group(P = 0.045). The abundances of the phylum Firmicutes and the family Lachnospiraceae(phylum Firmicutes, class Clostridia)(P = 0.009) were decreased in the responders within the prebiotic group. In addition, the proportions of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were inversely correlated with several fecal SCFAs(P 0.05).CONCLUSION Alterations in gut microbiota composition, including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria, following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.     

Bile acids and microbes in metabolic disease

Bile acids (BAs) serve as physiological detergents that enable the intestinal absorption and transportation of nutrients, lipids and vitamins. BAs are primarily produced by humans to catabolize cholesterol and play crucial roles in gut metabolism, microbiota habitat regulation and cell signaling. BA-activated nuclear receptors regulate the enterohepatic circulation of BAs which play a role in energy, lipid, glucose, and drug metabolism. The gut microbiota plays an essential role in the biotransformation of BAs and regulates BAs composition and metabolism. Therefore, altered gut microbial and BAs activity can affect human metabolism and thus result in the alteration of metabolic pathways and the occurrence of metabolic diseases/syndromes, such as diabetes mellitus, obesity/hypercholesterolemia, and cardiovascular diseases. BAs and their metabolites are used to treat altered gut microbiota and metabolic diseases. This review explores the increasing body of evidence that links alterations of gut microbial activity and BAs with the pathogenesis of metabolic diseases. Moreover, we summarize existing research on gut microbes and BAs in relation to intracellular pathways pertinent to metabolic disorders. Finally, we discuss how therapeutic interventions using BAs can facilitate microbiome functioning and ease metabolic diseases.