Short Chain Fatty Acid

短链脂肪酸
  • 文章类型: Journal Article
    在这项研究中,沙棘油(SBO)的影响,血清中的鱼油(FO)和酶合成的结构脂质(SL),研究了Sprague-Dawley(SD)大鼠的短链脂肪酸(SCFAs)和肠道菌群。结果表明,FO,SBO,SL可有效降低SD大鼠血清中高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平。SBO增加血清甘油三酯水平,而FO升高了总胆固醇水平。此外,所有三种膳食脂质都会降低短链脂肪酸的产生,并增强肠道微生物群的多样性。FO增加了肠道微生物群的丰度,包括Romboutsia,乳酸菌,大肠杆菌志贺氏菌,和落叶松科_NK4A136_组。相反,所有三种膳食脂质都降低了克雷伯氏菌和布劳特氏菌的丰度。这些发现为理解SBO和FO的功能以及它们在合成新型SL以调节肠道微生物群的潜在应用提供了基础。
    In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague-Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.
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  • 文章类型: Journal Article
    目的是调查增长绩效,抗氧化酶活性,肠道形态学,免疫细胞分布,短链脂肪酸(SCFA)谱,饲喂含有副干酪乳杆菌NSMJ15的日粮的肉鸡和微生物群。
    在随机完全区组设计中将总共120天大的Ross308雄性肉鸡分配给2种饮食处理。对照组饲喂玉米豆粕对照日粮,补充NSMJ15的组以玉米淀粉为代价,饲喂补充1g/kg副干酪乳杆菌NSMJ15的对照饮食。每种饮食处理具有6个重复,每个笼10只鸟。在第9天记录生长表现。在第10天,选择一只代表中位体重的鸟收集血清进行抗氧化酶活性,免疫细胞分离和形态分析的空肠组织,和盲肠消化进行16SrRNA基因测序和SCFA分析。
    副干酪乳杆菌NSMJ15的补充不影响生长性能,血清抗氧化酶活性,空肠组织形态学与对照组比较。在NSMJ15补充的组中,CD3+CD4+CD8-T细胞的数量增加(p=0.010),与对照组相比,CD3+CD8+TCRγδ+T细胞的数量减少(p=0.022)。与对照组相比,补充副干酪乳杆菌NSMJ15降低了盲肠消化物中的乙酸浓度(p=0.022)。16SrRNA基因测序分析表明,与对照组相比,NSMJ15补充组差异表达(p<0.05)10个扩增子序列变体,而不影响盲肠微生物群的α和β多样性指数。地中海杆菌属和阴杆菌属与CD4+T细胞呈正相关(p<0.05),而Gemmiger属,球菌,塞利莫纳斯,微生物菌群,Blautia与SCFA浓度呈负相关(p<0.05)。
    本研究的结果表明,饲粮中添加副干酪乳杆菌NSMJ15可以通过增加特定微生物属的差异表达来增加肉鸡的CD4T细胞百分比并降低乙酸盐浓度。
    UNASSIGNED: The objective was to investigate growth performance, antioxidant enzyme activity, intestinal morphology, immune cell distribution, short chain fatty acid (SCFA) profile, and microbiota in broiler chickens fed a diet containing Lacticaseibacillus paracasei NSMJ15.
    UNASSIGNED: A total of 120-day-old Ross 308 male broilers were allocated to 2 dietary treatments in a randomized complete block design. A control group was fed a corn-soybean meal control diet, and an NSMJ15-supplemented group was fed a control diet supplemented with 1 g/kg L. paracasei NSMJ15 at the expense of cornstarch. Each dietary treatment had 6 replicates with 10 birds per cage. Growth performance was recorded on day 9. On day 10, one bird representing median body weight was selected to collect serum for antioxidant enzyme activity, jejunal tissue for immune cell isolation and morphometric analysis, and cecal digesta for 16S rRNA gene sequencing and SCFA analysis.
    UNASSIGNED: Supplementation of L. paracasei NSMJ15 did not affect growth performance, serum antioxidant enzyme activity, and jejunal histomorphology compared to the control group. In the NSMJ15-supplemented group, the population of CD3+CD4+CD8- T cells increased (p=0.010), while the population of CD3+CD8+TCRγδ+ T cells decreased (p=0.022) compared to the control group. The L. paracasei NSMJ15 supplementation decreased (p=0.022) acetate concentration in the cecal digesta compared to the control group. The 16S rRNA gene sequencing analysis showed that NSMJ15-supplemented group differentially expressed (p<0.05) 10 more amplicon sequence variants compared to control group without affecting alpha and beta diversity indices of the cecal microbiota. Genera Mediterraneibacter and Negativibacillus were positively (p<0.05) correlated with CD4+ T cells, while genera Gemmiger, Coprococcus, Sellimonas, Massilimicrobiota, and Blautia were negatively (p<0.05) correlated with SCFA concentration.
    UNASSIGNED: The results of the present study suggest dietary L. paracasei NSMJ15 supplementation may increase percentage of CD4+ T cells and decrease acetate concentration in broiler chickens by increasing the differential expression of specific microbial genera.
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  • 文章类型: Journal Article
    G蛋白偶联受体是协调许多生理功能的不同种类的细胞表面受体。G蛋白偶联受体,GPR41和GPR43,有义短链脂肪酸(SCFA),它们是宿主肠道细菌饮食发酵的代谢产物。由于SCFA介导的对宿主肠道健康的有益作用,这些受体作为针对各种疾病的潜在治疗靶标而受到关注。越来越多的证据表明这些受体的活性与慢性代谢性疾病有关,包括肥胖,糖尿病,炎症,和心血管疾病。然而,尽管使用各种策略进行了深入的研究,包括基因敲除(KO)小鼠模型,关于GPR41和GPR43在疾病治疗中的确切作用的证据仍然不一致.这里,我们全面回顾了对GPR41和GPR43活性基础的信号传导机制的功能研究的最新发现,并强调了它们在健康和疾病中的多方面作用.我们预计这些知识将指导未来的研究重点和有效治疗干预措施的发展。
    G-protein-coupled receptors are a diverse class of cell surface receptors that orchestrate numerous physiological functions. The G-protein-coupled receptors, GPR41 and GPR43, sense short-chain fatty acids (SCFAs), which are metabolites of dietary fermentation by the host\'s intestinal bacteria. These receptors have gained attention as potential therapeutic targets against various diseases because of their SCFA-mediated beneficial effects on the host\'s intestinal health. Mounting evidence has associated the activity of these receptors with chronic metabolic diseases, including obesity, diabetes, inflammation, and cardiovascular disease. However, despite intensive research using various strategies, including gene knockout (KO) mouse models, evidence about the precise roles of GPR41 and GPR43 in disease treatment remains inconsistent. Here, we comprehensively review the latest findings from functional studies of the signaling mechanisms that underlie the activities of GPR41 and GPR43, as well as highlight their multifaceted roles in health and disease. We anticipate that this knowledge will guide future research priorities and the development of effective therapeutic interventions.
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  • 文章类型: Journal Article
    目的:关于短链脂肪酸(SCFA)的人类研究,肠道微生物组,2型糖尿病(T2DM)是有限的。在这里,我们探讨了SCFA和T2DM之间的关联以及肠道微生物多样性对农村人群葡萄糖状态的影响。
    结果:我们对河南农村队列进行了横断面研究,并收集了粪便样本。通过16SrRNA和GC-MS测量肠道微生物群组成和粪便SCFA浓度。人口是根据SCFA的三元划分的,和logistic回归模型评估SCFA与T2DM之间的关系。广义线性模型测试了SCFA与肠道微生物多样性对葡萄糖指标(葡萄糖,HbAlc和胰岛素)。与总SCFA的最低三分位数相比,乙酸和丁酸,最高的三元组表现出更低的T2DM患病率,OR和95%CI为0.291(0.085-0.991),0.160(0.044-0.574)和0.171(0.047-0.620),分别。受限制的三次样条显示出近似逆的S形关联。我们还注意到ACE指数与戊酸最高三元对葡萄糖水平的相互作用(P相互作用=0.022),以及Shannon指数与丁酸中三元对胰岛素水平的相互作用(P相互作用=0.034)。Prevotella_9和Odoribacter与T2DM呈负相关,布劳特氏菌属与T2DM呈正相关。这些细菌是常见的产生SCFA的成员。
    结论:SCFA之间的反向S形关联(总SCFA,醋酸盐,观察到丁酸盐)和T2DM。随着肠道微生物多样性的增加,戊酸和丁酸改变葡萄糖状态。
    OBJECTIVE: Human studies about short-chain fatty acids (SCFAs), the gut microbiome, and Type 2 diabetes (T2DM) are limited. Here we explored the association between SCFAs and T2DM and the effects of gut microbial diversity on glucose status in rural populations.
    RESULTS: We performed a cross-sectional study from the Henan Rural Cohort and collected stool samples. Gut microbiota composition and faecal SCFA concentrations were measured by 16S rRNA and GC-MS. The population was divided based on the tertiles of SCFAs, and logistic regression models assessed the relationship between SCFAs and T2DM. Generalized linear models tested the interactions between SCFAs and gut microbial diversity on glucose indicators (glucose, HbAlc and insulin). Compared to the lowest tertile of total SCFA, acetate and butyrate, the highest tertile exhibited lower T2DM prevalence, with ORs and 95% CIs of 0.291 (0.085-0.991), 0.160 (0.044-0.574) and 0.171 (0.047-0.620), respectively. Restricted cubic spline demonstrated an approximately inverse S-shaped association. We also noted interactions of the ACE index with the highest tertile of valerate on glucose levels (P-interaction = 0.022) and the Shannon index with the middle tertile of butyrate on insulin levels (P-interaction = 0.034). Genus Prevotella_9 and Odoribacter were inversely correlated with T2DM, and the genus Blautia was positively associated with T2DM. These bacteria are common SCFA-producing members.
    CONCLUSIONS: Inverse S-shaped associations between SCFAs (total SCFA, acetate, and butyrate) and T2DM were observed. Valerate and butyrate modify glucose status with increasing gut microbial diversity.
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  • 文章类型: Journal Article
    心力衰竭(HF)是一个全球性的公共卫生问题,发病率和死亡率逐年上升。肠道微生物组以多种方式积极影响人体的生理和病理活动。越来越多的研究表明,HF与肠道微生物代谢产物之间存在很强的相关性。我们的综述总结了这些代谢物的特定变化及其与HF进展的联系,旨在考虑调节肠道微生物组并使用其代谢途径治疗HF的新方法,有可能降低HF的发病率和死亡率以及改善预后。
    Heart failure (HF) is a global public health problem, with morbidity and mortality increasing year by year. The gut microbiome actively affects the physiological and pathological activities of the human body in a variety of ways. More and more studies have suggested a strong correlation between HF and gut microbiome metabolites. Our review summarizes the specific alteration of these metabolites and their connection to the progression of HF, aiming at considering new approaches toward regulating the gut microbiome and using its metabolic pathways to treat HF, potentially decreasing the morbidity and mortality of HF as well as improving prognosis.
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  • 文章类型: Journal Article
    蓬勃发展的蘑菇产业设想了经济优势,大量未利用的废物产生(~20%)为价值化创造了机会。壳聚糖,一种生物活性多糖,因其宝贵的治疗潜力而引起了极大的关注。因此,本研究旨在从蘑菇废物(MCH)中提取壳聚糖,以获得其益生元潜力。MCH的结构表征使用NMR,FTIR,和XRD。MCH的CP/MAS-13CNMR谱出现在δ57.67(C2),61.19(C6),75.39(C3/C5),83.53(C4),105.13(C1),23.69(CH3),和174.19(C=O)ppm。FTIR在3361cm-1、1582cm-1和1262cm-1处显示出归因于-NH拉伸的特征峰,酰胺II,和MCH的酰胺III带。MCH的XRD解释在2θ=20.19处表现出单一的强反射,这可能对应于“II型”多晶型物。提取的MCH(〜47kDa)表现出不同程度的脱乙酰作用,从79%到84%。补充益生菌菌株(干酪乳杆菌,L.Helveticus,植物乳杆菌,和鼠李糖)。MCH提高了乳酸菌的生长和SCFA的水平,特别是鼠李糖乳杆菌。MCH还抑制了病原菌的生长(对大肠杆菌和金黄色葡萄球菌的MIC为0.125和0.25mg/mL,分别)和增强益生菌的粘附效率(在补充1%MCH时为3%至8%)。在存在MCH的情况下,鼠李糖乳杆菌对病原体的效率更高,如抗粘连试验所示。这些发现表明,从蘑菇废物中提取的多糖可以用作改善肠道生态失调的益生元。
    The booming mushroom industry envisages economic merits, and massive unutilized waste production (∼ 20 %) creates an opportunity for valorization. Chitosan, a bioactive polysaccharide, has drawn immense attention for its invaluable therapeutic potential. Thus, the present study was conducted to extract chitosan from mushroom waste (MCH) for its prebiotic potential. The structural characterization of MCH was carried out using NMR, FTIR, and XRD. The CP/MAS-13CNMR spectrum of MCH appeared at δ 57.67 (C2), 61.19 (C6), 75.39 (C3/C5), 83.53 (C4), 105.13 (C1), 23.69 (CH3), and 174.19 (C = O) ppm. The FTIR showed characteristic peaks at 3361 cm-1, 1582 cm-1, and 1262 cm-1 attributed to -NH stretching, amide II, and amide III bands of MCH. XRD interpretation of MCH exhibited a single strong reflection at 2θ =20.19, which may correspond to the \"form-II\" polymorph. The extracted MCH (∼ 47 kDa) exhibited varying degrees of deacetylation from 79 to 84 %. The prebiotic activity score of 0.73 to 0.82 was observed for MCH (1 %) when supplemented with probiotic strains (Lactobacillus casei, L. helveticus, L. plantarum, and L. rhamnosus). MCH enhanced the growth of Lactobacillus strains and SCFA\'s levels, particularly in L. rhamnosus. The MCH also inhibited the growth of pathogenic strains (MIC of 0.125 and 0.25 mg/mL against E. coli and S. aureus, respectively) and enhanced the adhesion efficiency of probiotics (3 to 8 % at 1 % MCH supplementation). L. rhamnosus efficiency was higher against pathogens in the presence of MCH, as indicated by anti-adhesion assays. These findings suggested that extracted polysaccharides from mushroom waste can be used as a prebiotic for ameliorating intestinal dysbiosis.
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  • 文章类型: Journal Article
    微生物群领域的当代研究表明,共生细菌影响人类不同器官和系统的生理活动。比如大脑,肺,免疫和代谢系统。这种影响是通过各种过程实现的。其中之一是免疫机制的槽调节。已知微生物群和人类免疫系统之间的相互作用是复杂和模糊的。树突状细胞(DC)是独特的细胞,启动适应性免疫反应的发展和极化。这些细胞还将天然和特异性免疫反应性相互连接。来自微生物群的大量生化信号以不同的微生物群相关分子模式(MAMPs)和细菌代谢物的形式在人类生物体中局部和远处起作用。因此,共生细菌会影响树突状细胞的成熟度和活性,并影响人体的整体免疫反应性。然后确定对病原微生物的反应,炎症,与不同的病理状况相关,甚至影响疫苗接种的有效性。
    Contemporary research in the field of microbiota shows that commensal bacteria influence physiological activity of different organs and systems of a human organism, such as brain, lungs, immune and metabolic systems. This influence is realized by various processes. One of them is trough modulation of immune mechanisms. Interactions between microbiota and the human immune system are known to be complex and ambiguous. Dendritic cells (DCs) are unique cells, which initiate the development and polarization of adaptive immune response. These cells also interconnect native and specific immune reactivity. A large set of biochemical signals from microbiota in the form of different microbiota associated molecular patterns (MAMPs) and bacterial metabolites that act locally and distantly in the human organism. As a result, commensal bacteria influence the maturity and activity of dendritic cells and affect the overall immune reactivity of the human organism. It then determines the response to pathogenic microorganisms, inflammation, associated with different pathological conditions and even affects the effectiveness of vaccination.
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  • 文章类型: Journal Article
    背景:炎症性肠病(IBD)存在致癌风险,随着IBD的持续时间而升级。持续的组织学炎症被认为是结肠炎癌变的驱动因素。有效控制炎症有助于预防和治疗结肠炎相关性结直肠癌(CAC)。安昌玉阳汤(AYD),中药(TCM)配方,起源于中医古老的治疗结肠炎和大肠癌的方剂。AYD已证明在治疗IBD和潜在的抗癌特性方面的功效。
    目的:本研究旨在评估AYD改善AOM/DSS诱导的实验性结肠炎相关癌变的疗效。它进一步寻求通过整合多种组学测序方法来阐明其潜在机制。
    方法:使用氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)建立大鼠结肠炎相关癌变模型。UPLC-MS鉴定了AYD的化学成分。大鼠口服不同剂量的AYD(18.37、9.19和4.59g/kg)53天,以美沙拉嗪作为阳性对照。该研究通过检查腺瘤数量来评估抗癌作用,腺瘤负荷,异常隐窝病灶(ACF),组织病理学损伤,和肿瘤相关蛋白表达。通过体重评估抗炎和修复作用,疾病活动指数(DAI),结肠长度,脾脏指数,炎性细胞因子水平,和紧密连接蛋白表达。通过16SrRNA测序探讨了对肠道菌群和宿主代谢的影响,靶向短链脂肪酸(SCFA)代谢组学,和非靶向结肠代谢组学。通过转录组测序鉴定潜在的AYD靶标,并通过qRT-PCR和蛋白质印迹进行验证。
    结果:AYD显著减少腺瘤数量,腺瘤负荷,肿瘤相关病变,ACF,和肿瘤相关蛋白表达(例如,p53,PCNA)在AOM/DSS诱导的大鼠中,从而阻碍结肠炎相关癌变的进展。AYD还减轻了组织病理学损伤和炎症,促进肠粘膜屏障修复。此外,AYD调节肠道菌群结构,增强的SCFA生产,和调节结肠代谢物。转录组测序揭示了对过氧化物酶体增殖物激活受体(PPAR)信号通路的显著影响。随后的qRT-PCR和蛋白质印迹实验表明AYD在上调PPAR-γ和下调PPAR-α中的影响,PPAR-β/δ,和相关蛋白质(血栓调节蛋白[Thbd],脂肪酸结合蛋白5[Fabp5],硬脂酰辅酶A去饱和酶2[Scd2],磷脂转移蛋白[Pltp])。
    结论:本研究证明了AYD抑制AOM/DSS诱导的实验性结肠炎相关癌变的能力。其机制可能涉及PPAR信号通路的调节,影响肠道菌群和宿主代谢平衡。
    BACKGROUND: Inflammatory bowel disease (IBD) presents a risk of carcinogenesis, which escalates with the duration of IBD. Persistent histological inflammation is considered to be the driving factor of colitis carcinogenesis. Effective control of inflammation is helpful to prevent and treat colitis-related colorectal cancer (CAC). Anchang Yuyang Decoction (AYD), a traditional Chinese medicine (TCM) formula, is originated from the ancient prescription of TCM for treating colitis and colorectal cancer. AYD has demonstrated efficacy in treating IBD and potential anti-carcinogenic properties.
    OBJECTIVE: This research aims to assess the therapeutic efficacy of AYD in ameliorating experimental colitis-related carcinogenesis induced by AOM/DSS. It further seeks to elucidate its potential mechanisms by integrating multiple omics sequencing approaches.
    METHODS: A rat model for colitis-related carcinogenesis was developed using azoxymethane (AOM)/dextran sulfate sodium (DSS). UPLC-MS identified AYD\'s chemical constituents. Rats were administered varying doses of AYD (18.37, 9.19 and 4.59 g/kg) orally for 53 days, with mesalazine as a positive control. The study evaluated anti-carcinogenic effects by examining adenoma number, adenoma load, abnormal crypt foci (ACF), histopathological damage, and tumor-related protein expression. Anti-inflammatory and reparative effects were assessed through body weight, disease activity index (DAI), colon length, spleen index, inflammatory cytokine levels, and tight junction protein expression. The effects on intestinal microbiota and host metabolism were explored through 16S rRNA sequencing, targeted short-chain fatty acid (SCFA) metabonomics, and non-targeted colon metabolomics. Potential AYD targets were identified through transcriptomic sequencing and validated by qRT-PCR and western blotting.
    RESULTS: AYD significantly reduced adenoma number, adenoma load, neoplasm-associated lesions, ACF, and tumor-related protein expression (e.g., p53, PCNA) in AOM/DSS-induced rats, thus impeding colitis-related carcinogenesis progression. AYD also alleviated histopathological damage and inflammation, promoting intestinal mucosal barrier repair. Furthermore, AYD modulated intestinal flora structure, enhanced SCFA production, and regulated colon metabolites. Transcriptomic sequencing revealed a significant impact on the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Subsequent qRT-PCR and western blotting experiments indicated AYD\'s influence in up-regulating PPAR-γ and down-regulating PPAR-α, PPAR-β/δ, and related proteins (thrombomodulin [Thbd], fatty acid binding protein 5 [Fabp5], stearoyl-CoA desaturase 2 [Scd2], phospholipid transfer protein [Pltp]).
    CONCLUSIONS: This study demonstrates AYD\'s ability to inhibit experimental colitis-related carcinogenesis induced by AOM/DSS. Its mechanism likely involves modulation of the PPAR signaling pathway, impacting intestinal microbiota and host metabolic equilibrium.
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  • 文章类型: Journal Article
    苹果皮是一种典型的富含功能成分的木质纤维素食品副产品。在这项工作中,苹果果皮用米曲霉固态发酵,旨在调节其组成和生物活性。结果表明,米曲霉发酵基本上定制了组成,提高了苹果皮的抗氧化活性和益生元潜力。发酵后,1)游离酚类物质增加,抗氧化活性提高;2)果胶物质显著降解,随着可溶性膳食纤维的减少,而不溶性膳食纤维的增加;3)体外发酵能力增加,如总酸产量增加所示。肠道微生物群具有更多促进健康的潜力,如较高的乳酸菌丰度,双歧杆菌,Megamonas和Prevotella-9以及肠杆菌和大肠杆菌志贺氏菌的丰度较低。这项工作有利于苹果皮作为食品配方中潜在成分的改性。
    Apple peel is a typical lignocellulosic food by-product rich in functional components. In this work, apple peel was solid-state fermented with Aspergillus oryzae with an aim to modulate its composition and bioactivity. The results showed that A. oryzae fermentation substantially tailored the composition, improved the antioxidant activity and prebiotic potential of apple peel. Upon the fermentation, 1) free phenolics increased and antioxidant activity improved; 2) the pectin substances degraded significantly, along with a decrease in soluble dietary fiber while an increase in insoluble dietary fiber; 3) the in vitro fermentability increased as indicated by the increase in total acid production. The gut microbiota was shaped with more health-promoting potentials, such as higher abundances of Lactobacillus, Bifidobacterium, Megamonas and Prevotella-9 as well as lower abundances of Enterobacter and Echerichia-Shigella. This work is conducive to the modification of apple peel as a potential ingredient in food formulations.
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  • 文章类型: Journal Article
    肾尿酸结石(UAS)的高复发率对泌尿科医师提出了重大挑战,柠檬酸氢钠钾(PSHC)已被证明是一种有效的口服溶出药物。然而,尚无研究调查PSHC在结石溶解治疗期间对肠道微生物群及其代谢产物的影响.我们前瞻性招募了37名UAS患者和40名健康受试者,其中12名患者完成了为期3个月的药物干预。抽取空腹静脉血,保留中段尿液进行生化检测。收集粪便样品进行16S核糖体RNA(rRNA)基因测序和短链脂肪酸(SCFA)含量测定。UAS患者表现出合并症,如肥胖,高血压,痛风,和血脂异常。UAS患者的肠道微生物群的丰富度和多样性显着降低,拟杆菌属和梭杆菌属为优势属,而下颗粒属和双歧杆菌属富集较差。PSHC干预后,结石大小显著减少,同时血尿酸降低和尿pH值升高.干预后病原菌梭杆菌的丰度显著下调,而在产生SCFA的细菌中观察到了一种上调,导致丁酸含量显著升高。在PSHC干预后,与微生物群内脂肪酸合成和氨基酸代谢相关的功能显示出上调。相关分析显示结石病原菌丰度与结石形成的临床因素呈正相关,而与SCFA含量呈负相关。我们的初步研究表明,肠道微生物群和代谢物的改变是PSHC干预的关键生理适应。微生物群和SCFA的靶向调节有望提高药物治疗效果和预防结石复发。KEYPOINTS:•BacteroidesandFusobacteriumwereidentifiedasdominantgeneriaforUASpatients•AfterPSHCintervention,梭杆菌减少,丁酸含量增加•PSHC干预后,微生物群增加脂肪酸合成的能力。
    The high recurrence rate of renal uric acid stone (UAS) poses a significant challenge for urologists, and potassium sodium hydrogen citrate (PSHC) has been proven to be an effective oral dissolution drug. However, no studies have investigated the impact of PSHC on gut microbiota and its metabolites during stone dissolution therapy. We prospectively recruited 37 UAS patients and 40 healthy subjects, of which 12 patients completed a 3-month pharmacological intervention. Fasting vein blood was extracted and mid-stream urine was retained for biochemical testing. Fecal samples were collected for 16S ribosomal RNA (rRNA) gene sequencing and short chain fatty acids (SCFAs) content determination. UAS patients exhibited comorbidities such as obesity, hypertension, gout, and dyslipidemia. The richness and diversity of the gut microbiota were significantly decreased in UAS patients, Bacteroides and Fusobacterium were dominant genera while Subdoligranulum and Bifidobacterium were poorly enriched. After PSHC intervention, there was a significant reduction in stone size accompanied by decreased serum uric acid and increased urinary pH levels. The abundance of pathogenic bacterium Fusobacterium was significantly downregulated following the intervention, whereas there was an upregulation observed in SCFA-producing bacteria Lachnoclostridium and Parasutterella, leading to a significant elevation in butyric acid content. Functions related to fatty acid synthesis and amino acid metabolism within the microbiota showed upregulation following PSHC intervention. The correlation analysis revealed a positive association between stone pathogenic bacteria abundance and clinical factors for stone formation, while a negative correlation with SCFAs contents. Our preliminary study revealed that alterations in gut microbiota and metabolites were the crucial physiological adaptation to PSHC intervention. Targeted regulation of microbiota and SCFA holds promise for enhancing drug therapy efficacy and preventing stone recurrence. KEY POINTS: • Bacteroides and Fusobacterium were identified as dominant genera for UAS patients • After PSHC intervention, Fusobacterium decreased and butyric acid content increased • The microbiota increased capacity for fatty acid synthesis after PSHC intervention.
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