fusobacterium

梭杆菌
  • 文章类型: Journal Article
    背景和目的:代谢功能障碍相关脂肪性肝炎(MASH)相关肝细胞癌(HCC)的发病率在全球范围内呈上升趋势。伴随着肥胖和代谢综合征的流行。根据关于肝癌和牙周炎的潜在关联的初步报告,本研究旨在分析MASH相关HCC(MASH-HCC)中牙周细菌的参与以及口腔和肠道细菌菌群。材料和方法:41例MASH患者和19例MASH-HCC患者参与了研究,完成调查问卷,正在进行牙周检查,提供唾液样本,漱口水,粪便,和外周血。通过16S核糖体RNA测序分析口腔和粪便微生物组谱。采用贝叶斯网络分析法分析各因素之间的因果关系,包括MASH-HCC,考试,和细菌。结果:与MASH组相比,MASH-HCC组的肠道微生物区系中梭杆菌属的占有率明显更高(p=0.002)。然而,Butyricicocus(p=0.022)和Roseburia(p<0.05)的占有率显着降低。贝叶斯网络分析显示,不存在影响HCC的牙周致病菌和肠道细菌。然而,HCC直接影响牙周细菌牙龈卟啉单胞菌,连翘坦菌,具核梭杆菌,和唾液中中中膜普雷沃氏菌,以及乳杆菌属,罗斯布里亚,梭杆菌,普雷沃氏菌,梭菌属,Ruminococus,锥虫,和肠道中的SMB53。此外,口腔中的牙龈卟啉单胞菌直接影响肠道中的乳杆菌属和链球菌属。结论:MASH-HCC直接影响牙周致病菌和肠道细菌,牙龈卟啉单胞菌可能影响与胃肠道癌症相关的肠道细菌。
    Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.
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  • 文章类型: Journal Article
    微生物群落组成与宿主疾病的发生和进展密切相关,强调在各种健康环境中了解宿主微生物群动态的重要性。
    在这项研究中,我们利用全长16SrRNA基因测序对患有口腔恶性纤维瘤的大熊猫(Ailuropodamelanoleuca)口腔中的微生物进行物种级鉴定。
    我们观察到大熊猫口腔肿瘤侧和非肿瘤侧的微生物群落之间存在显着差异,后者表现出更高的微生物多样性。肿瘤侧以特定的微生物为主,比如镰刀菌,卟啉单胞菌sp.猫科动物口服分类单元110,弯曲杆菌。猫科动物口服分类单元100和奈瑟氏菌。猫口服分类单元078,据报道与其他生物体的致瘤过程和牙周疾病相关。根据线性判别分析效应大小分析,在肿瘤侧样本和非肿瘤侧样本之间获得了超过9种不同的生物标志物.此外,《京都基因和基因组百科全书》分析显示,大熊猫口腔微生物群与遗传信息处理和代谢显著相关,特别是辅因子和维生素,氨基酸,和碳水化合物代谢。此外,预计在肿瘤侧有明显的细菌侵袭上皮细胞。
    这项研究为大熊猫口腔微生物群与口腔肿瘤之间的关系提供了重要的见解,并提供了潜在的生物标志物,可以指导圈养和衰老大熊猫的未来健康评估和预防策略。
    UNASSIGNED: Microbial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host-microbiota dynamics in various health contexts.
    UNASSIGNED: In this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma.
    UNASSIGNED: We observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side.
    UNASSIGNED: This study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas.
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  • 文章类型: Journal Article
    背景:癌症微生物群被认为是癌症进展的主要危险因素。我们已经证明了牙周梭杆菌(F.p)在食管癌(EC)组织中丰度较高。生物信息分析发现,BCT是F.p.的关键毒力蛋白,对BCT在EC中的作用和机制知之甚少。本研究旨在识别F.p的关键毒力蛋白,探讨BCT促进EC的作用机制。
    方法:构建真核表达载体,纯化重组蛋白BCT。CCK8用于分析不同浓度BCT处理后EC的活性。UPLC-MS/MS和ELISA检测代谢组学和代谢产物。通过transwell测定完成迁移和侵袭能力。RT-QPCR,WB用于分析相关基因的表达。
    结果:我们的数据表明,BCT在EC肿瘤组织中的表达更高(p<0.05),BCT在20µg/mL中促进了生存率,EC细胞的侵袭和迁移(EC109)(p<0.05)。同时,UPLC-MS/MS结果表明,BCT导致了低牛磺酸代谢的增强,花生四烯酸代谢,糖酵解/糖异生,色氨酸代谢,EC109中的柠檬酸循环活性。代谢变化导致葡萄糖和丙酮酸水平降低,但乳酸脱氢酶(LDH)活性和乳酸(LA)活性增加以及调节糖酵解的葡萄糖转运蛋白1,己糖激酶2,LDH的表达均发生变化(p<0.05)。BCT处理上调TLR4、Akt、HIF-1α(p<0.05)调节LA的产生。此外,LA刺激促进GPR81、Wnt、和β-连环蛋白(p<0.05),从而在EC109细胞中诱导EMT和转移。
    结论:总而言之,这些发现确定了BCT在调节EC109糖酵解中的影响,其涉及TLR4/Akt/HIF-1α途径。同时,糖酵解通过GPR81/Wnt/β-catenin信号通路增加LA的释放并促进EC109的EMT。总之,我们的研究结果强调了靶向BCT作为缓解EC发展的创新策略的潜力.
    BACKGROUND: The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC.
    METHODS: We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes.
    RESULTS: Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and β-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells.
    CONCLUSIONS: Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/β-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.
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  • 文章类型: Case Reports
    背景:坏死梭杆菌(F.坏死)引起的坏死性肺炎是一种罕见但严重的肺部感染。微生物检测方法不足会导致诊断困难。
    方法:我们报告1例通过支气管肺泡灌洗液(BALF)的下一代测序(NGS)诊断为坏死F.肺脓肿。
    结果:BALF-NGS检测到F。指导后续靶向抗生素治疗。用主动引流和甲硝唑治疗,病人的病情得到有效治疗。
    结论:BALF-NGS是快速诊断由难以培养的细菌引起的感染的有价值的工具。它在坏死F.的早期鉴定中起着决定性的作用,能够及时和有针对性的抗生素干预。早期诊断和适当的治疗对于坏死F.肺炎的治疗至关重要。
    BACKGROUND: Fusobacterium necrophorum (F. necrophorum)-induced necrotizing pneumonia is a rare but severe pulmonary infection. Insufficient microbiological detection methods can lead to diagnostic difficulties.
    METHODS: We report a case of F. necrophorum lung abscess diagnosed by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF).
    RESULTS: BALF-NGS detected F. necrophorum, guiding subsequent targeted antibiotic therapy. With active drainage and metronidazole treatment, the patient\'s condition was effectively treated.
    CONCLUSIONS: BALF-NGS is a valuable tool for the rapid diagnosis of infections caused by difficult-to-culture bacteria. It played a decisive role in the early identification of F. necrophorum, enabling timely and targeted antibiotic intervention. Early diagnosis and appropriate treatment are crucial for the management of F. necrophorum pneumonia.
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  • 文章类型: Video-Audio Media
    背景:水产养殖在全球蛋白质供应和粮食安全中发挥着重要作用。禁止抗生素作为饲料添加剂,迫切需要开发替代品。肠道菌群在鱼类的代谢和免疫中起着重要作用,并有可能为鱼类养殖面临的挑战提供新的解决方案。然而,我们仍然缺乏对鱼类肠道微生物组的了解。
    结果:我们通过对草鱼肠道内容物样品的宏基因组测序鉴定了575,856个非冗余基因。基因目录的分类学和功能注释揭示了与哺乳动物相比,草鱼肠道微生物组的特异性。共现分析表明,属于变形杆菌的属与镰状杆菌/厚壁杆菌/拟杆菌属之间存在排他性关系,表明微生物群的两个独立的生态群。变形杆菌与鱼肠和肝脏的基因表达模块的关联模式始终与Fusobacteria相反,Firmicutes,和拟杆菌,暗示变形杆菌和梭杆菌/厚壁菌/拟杆菌的差异功能。因此,这两个生态群被认为是两个功能群,即,功能组1:变形菌和功能组2:梭杆菌/厚壁菌/拟杆菌。进一步的分析表明,这两个功能组的碳水化合物利用的遗传能力不同,毒力因子,抗生素耐药性。最后,我们提出,“功能组2/功能组1”的比例可以作为生物标志物,有效地反映草鱼微生物群的结构和功能特征。
    结论:基因目录是研究草鱼肠道微生物组的重要资源。多组学分析提供了对构成鱼类微生物群的主要门的功能影响的见解,并阐明了微生物群调节的目标。视频摘要。
    BACKGROUND: Aquaculture plays an important role in global protein supplies and food security. The ban on antibiotics as feed additive proposes urgent need to develop alternatives. Gut microbiota plays important roles in the metabolism and immunity of fish and has the potential to give rise to novel solutions for challenges confronted by fish culture. However, our understanding of fish gut microbiome is still lacking.
    RESULTS: We identified 575,856 non-redundant genes by metagenomic sequencing of the intestinal content samples of grass carp. Taxonomic and functional annotation of the gene catalogue revealed specificity of the gut microbiome of grass carp compared with mammals. Co-occurrence analysis indicated exclusive relations between the genera belonging to Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes, suggesting two independent ecological groups of the microbiota. The association pattern of Proteobacteria with the gene expression modules of fish gut and the liver was consistently opposite to that of Fusobacteria, Firmicutes, and Bacteroidetes, implying differential functionality of Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes. Therefore, the two ecological groups were considered as two functional groups, i.e., Functional Group 1: Proteobacteria and Functional Group 2: Fusobacteria/Firmicutes/Bacteroidetes. Further analysis revealed that the two functional groups differ in genetic capacity for carbohydrate utilization, virulence factors, and antibiotic resistance. Finally, we proposed that the ratio of \"Functional Group 2/Functional Group 1\" can be used as a biomarker that efficiently reflects the structural and functional characteristics of the microbiota of grass carp.
    CONCLUSIONS: The gene catalogue is an important resource for investigating the gut microbiome of grass carp. Multi-omics analysis provides insights into functional implications of the main phyla that comprise the fish microbiota and shed lights on targets for microbiota regulation. Video Abstract.
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  • 文章类型: Journal Article
    在这里,核梭杆菌ssp的三糖重复单元。动物ATCC51191,用于开发抗菌疫苗,首次有效合成。该合成方法具有以下特点:(i)使用岩藻胺C4处邻苯二甲酰亚胺基团的大空间位阻构建1,2-顺式-糖苷键;(ii)通过线性[21]糖基化策略合成三糖;(iii)使用六氟磷酸盐偶氮苯并三唑四甲基脲作为启动子安装1-丙氨酸。
    Herein, the trisaccharide repeating unit of Fusobacterium nucleatum ssp. animalis ATCC 51191, which is used to develop oncomicrobial vaccines, was efficiently synthesized for the first time. The synthetic approach featured the following: (i) construction of the 1,2-cis-glycosidic linkage using the large steric hindrance of a phthalimide group at C4 of fucosamine; (ii) synthesis of the trisaccharide via a linear [2 + 1] glycosylation strategy; and (iii) installation of l-alanine using hexafluorophosphate azabenzotriazole tetramethyl uronium as a promoter.
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  • 文章类型: Journal Article
    大肠杆菌RclA和金黄色葡萄球菌MerA是I组黄素蛋白二硫化物还原酶(FDR)家族的一部分,并且通过防御宿主免疫反应而参与了细菌发病机理的贡献。具核梭杆菌是一种病原体,厌氧性革兰氏阴性细菌物种通常在人类口腔和胃肠道中发现。在这项研究中,我们发现有核F蛋白FN0820属于I类FDR家族,显示比大肠杆菌RclA更高的Cu2依赖性NADH氧化酶活性。此外,FN0820降低了具有较高NADH氧化酶活性的溶液中的溶解氧水平。我们发现L-色氨酸及其类似物5-羟色氨酸抑制NADH氧化酶的FN0820活性以及伴随的氧减少。我们的结果对开发针对病原体的新治疗策略具有启示意义,这些病原体使用I组FDRs捍卫宿主免疫反应。
    Escherichia coli RclA and Staphylococcus aureus MerA are part of the Group I flavoprotein disulfide reductase (FDR) family and have been implicated in the contribution to bacterial pathogenesis by defending against the host immune response. Fusobacterium nucleatum is a pathogenic, anaerobic Gram-negative bacterial species commonly found in the human oral cavity and gastrointestinal tract. In this study, we discovered that the F. nucleatum protein FN0820, belonging to the Group I FDR family, exhibited a higher activity of a Cu2+-dependent NADH oxidase than E. coli RclA. Moreover, FN0820 decreased the dissolved oxygen level in the solution with higher NADH oxidase activity. We found that L-tryptophan and its analog 5-hydroxytryptophan inhibit the FN0820 activities of NADH oxidase and the concomitant reduction of oxygen. Our results have implications for developing new treatment strategies against pathogens that defend the host immune response with Group I FDRs.
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  • 文章类型: Journal Article
    当涉及烟雾病(MMD)的发作时,环境变量至关重要。此外,人们对肠道微生物组之间的关系感到困惑,环境变量,还有MMD。因此,为了确定引起MMD的特定细菌,我们检查了MMD个体和健康对照(HC)的肠道微生物组。
    从2021年6月至2022年5月进行了前瞻性病例对照调查。获得MMD和HC患者的粪便样品。通常,采用16SrRNA测序来检查它们的肠道微生物群。使用QIIME和R软件来检查数据。使用线性判别分析效应大小分析来确定生物标志物。通过线性模型(MaAsLin)2的多变量分析用于发现微生物组数据与临床变量之间的关联。使用接收器工作特性曲线和决策曲线分析评估模型性能。
    这项调查共涉及60名MMD患者和60名HC。MMD组的Shannon和Chao1指数明显低于HC组。β-多样性在加权UniFrac距离上有显著差异。在门一级,MMD组的梭菌/放线菌的相对丰度明显高于/低于HC组。通过MaAsLin2分析,2属的相对丰度,衣原体和梭杆菌,在MMD组中增加,而2属的相对丰度,MMD组的双歧杆菌和肠杆菌减少。利用这4个属构建了预测模型。受试者工作特性曲线下面积为0.921。决策曲线分析表明该模型在临床实践中具有实用性。
    MMD患者的肠道菌群发生了改变,其特点是衣原体和梭杆菌的丰度增加,双歧杆菌和肠杆菌的丰度降低。这4个属可用作临床实践中的生物标志物和预测因子。
    When it comes to the onset of moyamoya disease (MMD), environmental variables are crucial. Furthermore, there is confusion about the relationship between the gut microbiome, an environmental variable, and MMD. Consequently, to identify the particular bacteria that cause MMD, we examined the gut microbiome of MMD individuals and healthy controls (HC).
    A prospective case-control investigation was performed from June 2021 to May 2022. The fecal samples of patients with MMD and HC were obtained. Typically, 16S rRNA sequencing was employed to examine their gut microbiota. The QIIME and R softwares were used to examine the data. The linear discriminant analysis effect size analysis was used to determine biomarkers. Multivariate analysis by linear models (MaAsLin)2 were used to find associations between microbiome data and clinical variables. Model performance was assessed using the receiver operating characteristic curve and the decision curve analysis.
    This investigation involved a total of 60 MMD patients and 60 HC. The MMD group\'s Shannon and Chao 1 indices were substantially lower than those of the HC cohort. β-diversity was significantly different in the weighted UniFrac distances. At the phylum level, the relative abundance of Fusobacteriota/Actinobacteria was significantly higher/lower in the MMD group than that in the HC group. By MaAsLin2 analysis, the relative abundance of the 2 genera, Lachnoclostridium and Fusobacterium, increased in the MMD group, while the relative abundance of the 2 genera, Bifidobacterium and Enterobacter decreased in the MMD group. A predictive model was constructed by using these 4 genera. The area under the receiver operating characteristic curve was 0.921. The decision curve analysis indicated that the model had usefulness in clinical practice.
    The gut microbiota was altered in individuals with MMD, and was characterized by increased abundance of Lachnoclostridium and Fusobacterium and decreased abundance of Bifidobacterium and Enterobacter. These 4 genera could be used as biomarkers and predictors in clinical practice.
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  • 文章类型: Journal Article
    目的:本研究旨在调查儿童龋齿(DC)相关微生物组异常和代谢组学变化。
    方法:根据纳入和排除标准,将患者分为健康对照组(C组)和高度感染DC儿童。收集唾液样品并用于口腔微生物群的分类和功能表征。
    结果:超转录组学分析揭示了C组和DC组口腔微生物群的改变和组成。C组的相对丰度与Firmicutes相关,放线菌,和拟杆菌。然而,发现DC组中的微生物组成随着变形杆菌丰度的增加(25%)而显著改变,梭菌(15%),和蓝细菌(8%),而厚壁菌(10%)和拟杆菌(23%)的丰度降低。门组成的变化与糖的几种代谢物(例如果糖,山梨糖,核糖,合金,和甘露糖)和氨基酸(如精氨酸,赖氨酸,色氨酸,和脯氨酸)。此外,与C组相比,DC组的代谢转变随着某些三羧酸循环中间体水平的增加而不同,和脂肪酸的减少。这种改变可以增强口腔病原体的生长并有助于DC的发育。
    结论:这项研究的结果表明,放线杆菌的丰度改变,梭杆菌,和Shuttleworthia可以作为儿童DC的生物标志物。
    OBJECTIVE: The present study aims to investigate the variations in dental caries (DC) related microbiome abnormality and metabolomics shift in children.
    METHODS: The patients were divided into two groups healthy control (C) and highly affected DC children based on inclusion and exclusion criteria. Saliva samples were collected and used for the taxonomic and functional characterization of oral microbiota.
    RESULTS: Metatranscriptomics analysis revealed the alterations and composition of oral microbiota in the C and DC groups. Relative abundance in the C group was associated with Firmicutes, Actinobacteria, and Bacteroidetes. Whereas, the microbial composition in the DC group was found to be considerably altered with increases in the abundance of the Proteobacteria (25%), Fusobacteria (15%), and Cyanobacteria (8%) while decreases in the abundance of Firmicutes (10%) and Bacteroidetes (23%). Alterations in the phylum composition were positively and negatively correlated with several metabolites of sugars (such as fructose, sorbose, ribose, allose, and mannose) and amino acids (such as arginine, lysine, tryptophan, and proline). Moreover, in comparison with the C group, the metabolic shift of the DC group was different with an increase in certain tricarboxylic acid cycle intermediates levels, and a decrease in fatty acid. Such alterations can enhance the growth of oral pathogens and contribute to DC development.
    CONCLUSIONS: The findings of this study suggest that an altered abundance of Actinobacillus, Fusobacterium, and Shuttleworthia can serve as biomarkers of DC in children.
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  • 文章类型: Journal Article
    功能性便秘(FC)是一种高发病率的胃肠道疾病,其主要发病机制是肠神经系统功能障碍。为了增强我们对肠道微生物群及其代谢产物在FC发病机理中的作用的认识,我们对460名不同排便频率的中国女性进行了肠道菌群和血清短链脂肪酸(SCFAs)分析的鸟枪宏基因组测序分析.我们观察到梭菌的丰度,产生丁酸的细菌,与排便频率呈正相关(P=0.0096);然而,血清丁酸浓度与排便频率呈负相关(P=3.51E-05)。这些结果在独立队列(6名FC患者和6名对照)中得到证实。为进一步研究丁酸对肠神经细胞的影响,我们用不同浓度的丁酸盐(0.1,0.5,1和2.5mM)在体外处理小鼠肠神经元。我们发现,用0.5mM丁酸盐处理的肠神经元增殖比其他处理组更好,细胞周期和氧化磷酸化信号通路存在显著差异。我们建议,由于肠道微生物群中梭杆菌属丰度降低而导致的丁酸盐产生减少,会影响肠神经元的增殖和肠细胞的能量供应。然而,随着FC疾病的发展,丁酸的消耗和排泄减少,导致它在肠道中积累。此外,过量丁酸的积累抑制了神经细胞的增殖并随后加剧了疾病。
    Functional constipation (FC) is a high morbidity gastrointestinal disease for which dysfunction in the enteric nervous system is a major pathogenesis mechanism. To enhance our understanding of the involvement of intestinal microbiota and its metabolites in the pathogenesis of FC, we conducted a shotgun metagenomic sequencing analysis of gut microbiota and serum short-chain fatty acids (SCFAs) analysis in 460 Chinese women with different defecation frequencies. We observed that the abundance ofFusobacterium_varium, a butyric acid-producing bacterium, was positively correlated (P = 0.0096) with the frequency of defecation; however, the concentrations of serum butyric acid was negatively correlated (P = 3.51E-05) with defecation frequency. These results were verified in an independent cohort (6 patients with FC and 6 controls). To further study the effects of butyric acid on intestinal nerve cells, we treated mouse intestinal neurons in vitro with various concentrations of butyrate (0.1, 0.5, 1, and 2.5 mM). We found that intestinal neurons treated with 0.5 mM butyrate proliferated better than those in the other treatment groups, with significant differences in cell cycle and oxidative phosphorylation signal pathways. We suggest that the decreased butyrate production resulting from the reduced abundance of Fusobacterium in gut microbiota affects the proliferation of intestinal neurons and the energy supply of intestinal cells. However, with FC disease advancing, the consumption and excretion of butyric acid reduce, leading to its accumulation in the intestine. Moreover, the accumulation of an excessively high amount of butyric acid inhibits the proliferation of nerve cells and subsequently exacerbates the disease.
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