Intestinal microbiome

肠道微生物组
  • 文章类型: Journal Article
    炎症性肠病(IBD)是全球健康问题。芦荟大黄素(AE)具有多种药理益处,包括抗炎作用。然而,其在IBD中的作用尚不清楚,促使我们研究其在IBD小鼠模型中的调节作用和机制。
    我们研究了AE在葡聚糖硫酸钠(DSS)诱导的结肠炎的鼠模型中缓解症状和调节细胞因子分泌的治疗功效。向BALB/c小鼠施用DSS以诱导结肠炎,随后用不同剂量的AE治疗。体重的变化,粪便脂质运载蛋白-2(LCN2)水平,结肠组织组织学,评估和血清细胞因子浓度以评估AE治疗的效果。此外,16SrRNA测序用于分析AE干预后肠道微生物群组成的变化。最后,该数据库用于分析AE中与IBD相关的信号通路,并使用实时定量逆转录PCR检测白细胞介素(IL)-4通路的表达水平.将外源性IL-4用于抢救实验,观察其在AE调控下对IBD疾病过程的影响。
    AE治疗导致体重减轻的剂量依赖性缓解,粪便LCN2水平降低,并改善DSS诱导的小鼠结肠炎的组织学损伤。超氧化物歧化酶和过氧化氢酶的水平增加,而丙二醛在AE治疗后下降,表明结肠炎症状的剂量依赖性缓解。此外,AE给药减弱了促炎细胞因子的分泌,包括IL-17,肿瘤坏死因子-α(TNF-α),和趋化因子配体1,同时促进抗炎细胞因子IL-4和IL-13的表达。对肠道微生物群的分析表明,AE有效地抑制了结肠炎相关细菌的过度生长,并恢复了微生物的稳态。最后,我们发现IL-4的过表达能够逆转AE对DSS诱导的IBD的治疗效果。
    AE显示出缓解结肠炎严重程度的希望,影响炎症细胞因子,并通过IL-4/IL-13途径调节IBD小鼠模型中的肠道微生物群,表明其作为自然IBD治疗的潜力。
    UNASSIGNED: Inflammatory bowel disease (IBD) is a global health concern. Aloe-emodin (AE) has diverse pharmacological benefits, including anti-inflammatory effects. However, its role in IBD remains unclear, prompting our investigation of its regulatory effects and mechanisms in an IBD mouse model.
    UNASSIGNED: We studied the therapeutic efficacy of AE in alleviating symptoms and modulating cytokine secretion in a murine model of dextran sulfate sodium (DSS)-induced colitis. BALB/c mice were administered DSS to induce colitis and were subsequently treated with varying doses of AE. Changes in body weight, fecal lipocalin-2 (LCN2) levels, colon tissue histology, and serum cytokine concentrations were evaluated to assess the effects of AE treatment. Additionally, 16 S rRNA sequencing was used to analyze alterations in the composition of the gut microbiota following AE intervention. Finally, the database was used to analyze the signaling pathways associated with IBD in AE and to detect the expression levels of interleukin (IL)-4 pathway using real-time quantitative reverse transcription PCR. Exogenous IL-4 was used in rescue experiments to observe its effects on the disease process of IBD under AE regulation.
    UNASSIGNED: AE treatment resulted in a dose-dependent mitigation of weight loss, reduction in fecal LCN2 levels, and amelioration of histological damage in DSS-induced colitis in mice. The levels of superoxide dismutase and catalase increased, whereas malondialdehyde decreased following AE treatment, indicating a dose-dependent alleviation of colitis symptoms. Furthermore, AE administration attenuated the secretion of pro-inflammatory cytokines, including IL-17, tumor necrosis factor-alpha (TNF-α), and chemokine ligand 1, while promoting the expression of anti-inflammatory cytokines IL-4 and IL-13. Analysis of the gut microbiota revealed that AE effectively suppressed the overgrowth of colitis-associated bacterial species and restored microbial homeostasis. Finally, we found that overexpression of IL-4 was able to reverse the therapeutic effect of AE for DSS-induced IBD.
    UNASSIGNED: AE shows promise in alleviating colitis severity, influencing inflammatory cytokines, and modulating the gut microbiota in an IBD mouse model via the IL-4/IL-13 pathway, suggesting its potential as a natural IBD remedy.
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  • 文章类型: Journal Article
    背景:肠道微生物组被认为是可能导致抗磷脂综合征(APS)持久性抗体的因素。肠道微生物干预可以诱导和减轻小鼠的APS。在人类APS患者中,抗β-2-糖蛋白I(β2GP-1)滴度与针对与β2GP-1同源的肠道共生蛋白的抗体滴度相关。
    目的:研究肠道微环境对人体APS的影响。方法我们横截面比较了通过鸟枪测序定量的肠道微生物群组成;粪便短链脂肪酸(SCFA),已知会影响自身免疫过程的细菌代谢物;和粪便钙卫蛋白,肠道炎症标记物,APS患者和健康对照。
    结果:APS患者(n=15)和对照组(n=16)之间肠道菌群的α和β多样性均无差异,并且没有分类群差异丰富。此外,粪便SCFA和粪便钙卫蛋白,两组之间没有差异。
    结论:肠道微生物对APS表型的影响可能不是由细菌过多引起的,SCFA产生或肠道炎症。
    BACKGROUND: The gut microbiome is recognized as a factor that could potentially contribute to the persistent antibodies of antiphospholipid syndrome (APS). Gut microbial interventions can both induce and mitigate APS in mice. In human APS patients, anti-beta-2-glycoprotein I (β2GP-1) titers correlate with antibody titers against a gut commensal protein homologous to β2GP-1.
    OBJECTIVE: To  investigate the effect of the intestinal microenvironment on human APS. Methods We cross-sectionally compared intestinal microbiota composition quantified by shotgun sequencing; fecal short chain fatty acids (SCFAs), bacterial metabolites known to affect autoimmune processes; and fecal calprotectin, an intestinal inflammatory marker, in APS patients and healthy controls.
    RESULTS: Neither alpha nor beta diversity of the gut microbiota differed between APS patients (n = 15) and controls (n = 16) and no taxa were differentially abundant. Moreover, fecal SCFAs and fecal calprotectin, did not differ between the groups.
    CONCLUSIONS: Gut microbiome effects on the APS phenotype are likely not driven by bacterial overabundance, SCFA production or intestinal inflammation.
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  • 文章类型: Journal Article
    背景:射血分数保留的心力衰竭(HFpEF)与全身性炎症有关,肥胖,代谢综合征,和肠道微生物组的变化。三甲胺-N-氧化物(TMAO)水平升高是HFpEF死亡率的预测因素。TMAO前体三甲胺(TMA)由肠道微生物组合成,穿过肠屏障,并通过含肝黄素的单加氧酶(FMO)代谢为TMAO。这里分析了微生物组改变和TMAO与HFpEF表现和进展的复杂相互作用。
    方法:研究了具有HFpEF的健康瘦(L-ZSF1,n=12)和肥胖ZSF1大鼠(O-ZSF1,n=12)。经胸超声心动图证实HFpEF,侵入性血液动力学测量,并检测N末端脑钠肽前体(NT-proBNP)。TMAO,肉碱,对称二甲基精氨酸(SDMA),和氨基酸使用质谱法测量。通过免疫组织化学分析肠上皮屏障,体外阻抗测量和通过ELISA测定血浆脂多糖。通过Western印迹测定肝FMO3量。使用16srRNA扩增子测序评估8、13和20周龄的粪便微生物组。
    结果:TMAO水平增加(54%),在患有HFpEF的肥胖大鼠中观察到肉碱(46%)和心脏压力标志物NT-proBNP(25%)以及明显的氨基酸失衡。O-ZSF1中的SDMA水平与L-ZSF1相当,表明肾功能稳定。肠上皮中的解剖学和小带闭塞蛋白密度保持不变,但是阻抗测量和LPS水平升高均表明上皮屏障功能受损。FMO3在扩大时降低(-20%),但组织学正常的O-ZSF1肝脏。阿尔法多样性,如香农多样性指数所示,在8周龄时相当,但下降到13周龄,当HFpEF出现在O-ZSF1中时。Bray-Curtis差异(β-多样性)在20周龄时可有效区分L-ZSF1和O-ZSF1。乳杆菌科微生物家族的成员,Ruminocycaceae,在O-ZSF1和L-ZSF1大鼠中,Erypelotrichaceae和Lachnospienceae的含量显着不同。
    结论:在ZSF1HFpEF大鼠模型中,饮食摄入增加与肠道微生物组组成和细菌代谢产物的改变有关,肠屏障受损,以及促炎和健康预测代谢谱的变化。HFpEF及其最常见的合并症,肥胖和代谢综合征以及此处描述的改变是并行发展的,并且可能是相互关联和相辅相成的。饮食适应可能会对所有实体产生积极影响。
    BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here.
    METHODS: Healthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing.
    RESULTS: Increased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (- 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray-Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats.
    CONCLUSIONS: In the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities.
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  • 文章类型: Journal Article
    背景:抗磷脂综合征(APS)患者自身抗体的来源尚不清楚。肠道微生物组有助于自身免疫,并含有主要APS自身抗原的肽同源物,影响动物模型中的疾病活动。用万古霉素改变肠道微生物区会减少小鼠的疾病活动,但迄今为止尚无关于APS患者肠道微生物区系改变效果的数据。目的评估肠道菌群是否影响人APS的疾病活动。方法对病情稳定且无胃肠道合并症的APS患者进行术前设计干预研究。受试者接受口服万古霉素,500毫克,每天四次,持续7天,先前显示可以改变肠道微生物群组成,而不会产生系统性影响。在四个时间点通过测量一组临床表型相关的生物标志物来评估疾病活动:抗磷脂抗体(APLA),补体和炎症标志物,和止血参数。主要结果是通过多水平主成分分析确定的生物标志物组的复合。结果共有15名受试者完成研究。主要结果,生物标志物面板数据的第一主成分,万古霉素治疗7天后有显著差异(p=0.03),但不是在第42天.APLA滴度不受影响。出乎意料的是,15名患者中有4名在基线时对APLA呈阴性。在事后分析中,基线时抗体阳性的受试者有延长的效应(p=0.03).在基线APLAs阴性的受试者中,干预没有效果。结论APS患者肠道菌群影响生化疾病活动。该机制尚不清楚,但似乎是APS特异性的。
    Background  The origin of autoantibodies in patients with antiphospholipid syndrome (APS) is unknown. The gut microbiome contributes to autoimmunity and contains peptide homologues to the main APS autoantigen, which affect disease activity in animal models. Alteration of the gut microbiota with vancomycin diminishes disease activity in mice but no data on the effect of gut microbiota alteration in APS patients are available to date. Objective  To evaluate whether the gut microbiome affects disease activity in human APS. Methods  This was a pre-post design intervention study in APS patients with stable disease and no gastrointestinal comorbidity. Subjects received oral vancomycin, 500 mg four times daily for 7 days, previously shown to alter gut microbiota composition without systemic effects. Disease activity was assessed at four time points by measuring a panel of clinical phenotype-related biomarkers: antiphospholipid antibodies (APLAs), complement and inflammation markers, and hemostatic parameters. The primary outcome was the composite of the biomarker panel determined by multilevel principal component analysis. Results  A total of 15 subjects completed the study. The primary outcome, the first principal component of the biomarker panel data, was significantly different after 7 days of vancomycin treatment ( p  = 0.03), but not at day 42. APLA titers were unaffected. Unexpectedly, 4 out of 15 patients were negative for APLAs at baseline. In a post-hoc analysis, there was a prolonged effect for subjects with positive antibodies at baseline ( p  = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. Conclusion  The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    牦牛(Bosgrunniens)具有出色的区域适应性,使其能够在青藏高原独特的生态位中茁壮成长。它的生存依赖于肠道微生物组的复杂平衡,适应恶劣的环境条件。尽管有文献记载的细菌和真菌在维持肠道稳态和支持免疫功能方面具有重要意义,在理解牦牛肠道微生物群的组成和功能如何沿海拔-温度梯度变化方面仍有很大差距。这项研究旨在通过采用16SrRNA和ITS扩增子测序技术来分析和比较不同海拔和暴露于不同温度的牦牛的肠道微生物组,从而填补这一空白。研究结果表明,肠道细菌和真菌的多样性存在细微差异,伴随着各种海拔高度和温度梯度的分类组成发生重大变化。值得注意的是,Firmicutes,放线菌,拟杆菌在所有群体中都是占主导地位的门,放线菌在LZF组中的比例最高(35.77%)。功能预测分析揭示了LZF组和氨基酸代谢和生物合成相关的代谢途径之间的显著关联。这表明放线菌在增强牦牛营养吸收和代谢方面具有潜在作用。此外,我们的发现表明,牦牛的微生物群可能通过调节厚壁菌与拟杆菌的比例来增强能量代谢和分解代谢,有可能减轻温度变化的影响。使用宏基因组技术分析了三个不同组之间的肠道细菌和真菌群落的变化。我们的发现表明,在低海拔地区牦牛中表现出显着增加的微生物属在很大程度上是有益的。总而言之,我们的研究调查了不同海拔和温度范围内牦牛肠道细菌和真菌种群的变化。此外,这些结果增强了对肠道微生物组成和变异性的理解,从微生物的角度提供了关于干批牦牛的环境恢复能力的观点。
    The yak (Bos grunniens) exhibits exceptional regional adaptability, enabling it to thrive in the distinctive ecological niches of the Qinghai-Tibet Plateau. Its survival relies on the intricate balance of its intestinal microbiome, essential for adapting to harsh environmental conditions. Despite the documented significance of bacteria and fungi in maintaining intestinal homeostasis and supporting immune functions, there is still a substantial gap in understanding how the composition and functionality of yak gut microbiota vary along altitude-temperature gradients. This study aims to fill this gap by employing 16S rRNA and ITS amplicon sequencing techniques to analyze and compare the intestinal microbiome of yaks residing at different elevations and exposed to varying temperatures. The findings demonstrate subtle variations in the diversity of intestinal bacteria and fungi, accompanied by significant changes in taxonomic composition across various altitudes and temperature gradients. Notably, Firmicutes, Actinobacteriota, and Bacteroidota emerged as the dominant phyla across all groups, with Actinobacteriota exhibiting the highest proportion (35.77%) in the LZF group. Functional prediction analysis revealed significant associations between the LZF group and metabolic pathways related to amino acid metabolism and biosynthesis. This suggests a potential role for actinomycetes in enhancing nutrient absorption and metabolism in yaks. Furthermore, our findings suggest that the microbiota of yaks may enhance energy metabolism and catabolism by modulating the Firmicutes-to-Bacteroidota ratio, potentially mitigating the effects of temperature variations. Variations in gut bacterial and fungal communities among three distinct groups were analyzed using metagenomic techniques. Our findings indicate that microbial genera exhibiting significant increases in yaks at lower altitudes are largely beneficial. To sum up, our research investigated the changes in gut bacterial and fungal populations of yaks residing across diverse altitude and temperature ranges. Moreover, these results enhance comprehension of gut microbial makeup and variability, offering perspectives on the environmental resilience of dry lot feeding yaks from a microbial angle.
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  • 文章类型: Journal Article
    肠道菌群(GM)在人类健康中起着至关重要的作用,特别是在生命的最初几年。母乳喂养和配方奶(F)喂养的婴儿之间的转基因差异可能会影响长期健康结果。本系统评价旨在比较母乳喂养婴儿与F喂养婴儿的肠道微生物群,并评估这些差异的临床意义。我们搜索了Scopus的数据库,WebofScience,并发布以下关键词:“肠道微生物群”,“肠道微生物组”,和“新生儿奶”。纳入标准是与营养类型相关的新生儿肠道微生物组分析相关的文章,临床研究或病例系列,不包括评论,荟萃分析,动物模型,和体外研究。筛选阶段结束,为这项工作选择了13种出版物。母乳喂养的婴儿显示出更高水平的有益菌,如双歧杆菌和乳酸菌,而F喂养婴儿的潜在致病菌患病率较高,包括艰难梭菌和肠杆菌科。婴儿喂养方式对口服GM的组成有显著影响。母乳喂养促进更健康,更多样化的微生物生态系统,可以提供保护性健康益处。未来的研究应该探索改善F喂养婴儿转基因的策略,并了解长期健康影响。
    The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed infants with that of F-fed infants and to evaluate the clinical implications of these differences. We searched databases on Scopus, Web of Science, and Pubmed with the following keywords: \"gut microbiota\", \"gut microbiome\", and \"neonatal milk\". The inclusion criteria were articles relating to the analysis of the intestinal microbiome of newborns in relation to the type of nutrition, clinical studies or case series, excluding reviews, meta-analyses, animal models, and in vitro studies. The screening phase ended with the selection of 13 publications for this work. Breastfed infants showed higher levels of beneficial bacteria such as Bifidobacterium and Lactobacillus, while F-fed infants had a higher prevalence of potentially pathogenic bacteria, including Clostridium difficile and Enterobacteriaceae. Infant feeding type influences the composition of oral GM significantly. Breastfeeding promotes a healthier and more diverse microbial ecosystem, which may offer protective health benefits. Future research should explore strategies to improve the GM of F-fed infants and understand the long-term health implications.
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  • 文章类型: Journal Article
    腰背痛是一个健康问题,是多年残疾的最大原因。这项研究旨在评估两个相似组的肠道微生物群的细菌组成:一组患有慢性下腰痛(PG)和对照组(CG)。分析了来自73名参与者的临床数据和来自粪便样本的细菌基因组测序数据。PG中有40个人,CG中有33个人,年龄在20至50岁之间,体重指数高达30kg/m2。因此,群体内α多样性和群体间β多样性分析。显着结果(p<0.05)显示PG中的物种丰富度高于CG。此外,发现PG中艰难梭状芽孢杆菌的丰度更高,同时发现52个物种之间的平均相对丰度显着不同(调整后的p<0.05),PG中有36种更丰富的物种,CG中有16种。我们率先揭示了非老年人慢性腰背痛患者肠道细菌菌群组成的显着差异,非肥胖,没有任何其他严重的慢性疾病。它可以作为慢性腰痛中可能的肠道细菌微生物群特征的参考。
    Low back pain is a health problem that represents the greatest cause of years lived with disability. This research seeks to evaluate the bacterial composition of the intestinal microbiota of two similar groups: one with chronic low back pain (PG) and the control group (CG). Clinical data from 73 participants and bacterial genome sequencing data from stool samples were analyzed. There were 40 individuals in PG and 33 in CG, aged between 20 and 50 years and with a body mass index of up to 30 kg/m2. Thus, the intragroup alpha diversity and intergroup beta diversity were analyzed. The significant results (p < 0.05) showed greater species richness in PG compared to CG. Additionally, a greater abundance of the species Clostridium difficile in PG was found along with 52 species with significantly different average relative abundances between groups (adjusted p < 0.05), with 36 more abundant species in PG and 16 in CG. We are the first to unveil significant differences in the composition of the intestinal bacterial microbiota of individuals with chronic low back pain who are non-elderly, non-obese and without any other serious chronic diseases. It could be a reference for a possible intestinal bacterial microbiota signature in chronic low back pain.
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  • 文章类型: Journal Article
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  • 文章类型: Letter
    这是肠道微生物组和大肠癌之间的第一个文献计量学分析,分析现状和未来趋势。未来的年度出版物产量将不断增加。未来的研究热点将集中在新药开发上,发病机制研究和靶向治疗。
    This was the first bibliometric analysis between intestinal microbiome and colorectal cancer, analyzing the current status and future trends. The annual publication output would be constantly increasing in the future. Future research hotspots would focus on the new drugs development, pathogenesis research and targeted therapy.
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