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Bacterial extracellular vesicles at the interface of gut microbiota and immunity 肠道微生物群与免疫界面上的细菌胞外囊泡
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-28 DOI: 10.1080/19490976.2024.2396494
Inês Melo-Marques, Sandra Morais Cardoso, Nuno Empadinhas
Bacterial extracellular vesicles (BEVs) are nano-sized lipid-shielded structures released by bacteria and that play an important role in intercellular communication. Their broad taxonomic origins a...
细菌胞外囊泡(BEVs)是细菌释放的纳米级脂质屏蔽结构,在细胞间通信中发挥着重要作用。它们在分类学上有广泛的渊源。
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引用次数: 0
Changes in intestinal permeability and gut microbiota following diet-induced weight loss in patients with metabolic dysfunction-associated steatohepatitis and liver fibrosis 代谢功能障碍相关性脂肪性肝炎和肝纤维化患者节食减肥后肠道通透性和肠道微生物群的变化
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-28 DOI: 10.1080/19490976.2024.2392864
Dimitrios A. Koutoukidis, Sandi Yen, Paula Gomez Castro, Mariya Misheva, Susan A. Jebb, Paul Aveyard, Jeremy W. Tomlinson, Ferenc E. Mozes, Jeremy F. Cobbold, Jethro S. Johnson, Julian R. Marchesi
Weight loss improves metabolic dysfunction-associated steatohepatitis (MASH). We investigated whether there were associated changes in intestinal permeability, short-chain fatty acids (SCFAs), and ...
减肥能改善代谢功能障碍相关性脂肪性肝炎(MASH)。我们研究了肠道通透性、短链脂肪酸(SCFAs)和脂肪肝的相关变化。
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引用次数: 0
FMT rescues mice from DSS-induced colitis in a STING-dependent manner FMT 以 STING 依赖性方式挽救小鼠免于 DSS 引起的结肠炎
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-26 DOI: 10.1080/19490976.2024.2397879
Dan Pu, Yao Yao, Chuan Zhou, Ruixian Liu, Zhihong Wang, Yan Liu, Dandan Wang, Binbin Wang, Yaohe Wang, Zhanju Liu, Zhe Zhang, Baisui Feng
Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in ...
粪便微生物群移植(FMT)是目前治疗炎症性肠病(IBD)的一种很有前景的疗法。然而,临床研究表明,粪便微生物群移植在治疗炎症性肠病(IBD)方面存在明显的个体差异。
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引用次数: 0
Intestinal deguelin drives resistance to acetaminophen-induced hepatotoxicity in female mice. 雌性小鼠肠道 deguelin 对乙酰氨基酚诱导的肝毒性具有抗性。
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-21 DOI: 10.1080/19490976.2024.2404138
Shenhai Gong,Yunong Zeng,Ze Wang,Yanru Li,Rong Wu,Lei Li,Hongbin Hu,Ping Qin,Zhichao Yu,Xintao Huang,Peiheng Guo,Hong Yang,Yi He,Zhibin Zhao,Weidong Xiao,Xiaoshan Zhao,Lei Gao,Shumin Cai,Zhenhua Zeng
Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI), with gender-specific differences in susceptibility. However, the mechanism underlying this phenomenon remains unclear. Our study reveals that the gender-specific differences in susceptibility to APAP-induced hepatotoxicity are due to differences in the gut microbiota. Through microbial multi-omics and cultivation, we observed increased gut microbiota-derived deguelin content in both women and female mice. Administration of deguelin was capable of alleviating hepatotoxicity in APAP-treated male mice, and this protective effect was associated with the inhibition of hepatocyte oxidative stress. Mechanistically, deguelin reduced the expression of thyrotropin receptor (TSHR) in hepatocytes with APAP treatment through direct interaction. Pharmacologic suppression of TSHR expression using ML224 significantly increased hepatic glutathione (GSH) in APAP-treated male mice. These findings suggest that gut microbiota-derived deguelin plays a crucial role in reducing APAP-induced hepatotoxicity in female mice, offering new insights into therapeutic strategies for DILI.
对乙酰氨基酚(APAP)过量是药物性肝损伤(DILI)的主要病因,其易感性存在性别差异。然而,这一现象的机制仍不清楚。我们的研究发现,对 APAP 引起的肝毒性的易感性的性别差异是由肠道微生物群的差异造成的。通过微生物多组学和培养,我们观察到女性和雌性小鼠肠道微生物群衍生的脱氢甘油酯含量都有所增加。服用去瓜尔林能够减轻经 APAP 处理的雄性小鼠的肝毒性,这种保护作用与抑制肝细胞氧化应激有关。从机理上讲,deguelin 通过直接相互作用降低了经 APAP 处理的肝细胞中促甲状腺激素受体(TSHR)的表达。使用 ML224 对 TSHR 的表达进行药物抑制,可显著提高 APAP 处理的雄性小鼠肝脏谷胱甘肽(GSH)的含量。这些研究结果表明,肠道微生物群衍生的deguelin在降低APAP诱导的雌性小鼠肝毒性方面发挥着至关重要的作用,为DILI的治疗策略提供了新的思路。
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引用次数: 0
Akkermansia in the gastrointestinal tract as a modifier of human health 胃肠道中的 Akkermansia 是人类健康的调节剂
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-21 DOI: 10.1080/19490976.2024.2406379
Maria E. Panzetta, Raphael H. Valdivia
Akkermansia sp are common members of the human gut microbiota. Multiple reports have emerged linking the abundance of A. muciniphila to health benefits and disease risk in humans and animals. This ...
Akkermansia sp 是人类肠道微生物群的常见成员。已有多份报告指出,粘多糖与人类和动物的健康益处和疾病风险有关。这 ...
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引用次数: 0
A new perspective in intestinal microecology: lifting the veil of exercise regulation of cardiometabolic diseases. 肠道微生态学的新视角:揭开运动调节心脏代谢疾病的面纱。
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-21 DOI: 10.1080/19490976.2024.2404141
Can Gao,Jinwen Wei,Changxu Lu,Lijie Wang,Dan Dong,Mingli Sun
Cardiometabolic diseases (CMDs), encompassing cardiovascular and metabolic dysfunctions, characterized by insulin resistance, dyslipidemia, hepatic steatosis, and inflammation, have been identified with boosting morbidity and mortality due to the dearth of efficacious therapeutic interventions. In recent years, studies have shown that variations in gut microbiota and its own metabolites can influence the occurrence of CMDs. Intriguingly, the composition and function of the gut microbiota are susceptible to exercise patterns, thus affecting inflammatory, immune, and metabolic responses within the host. In this review, we introduce the key mechanisms of intestinal microecology involved in the onset and development of CMDs, discuss the relationship between exercise and intestinal microecology, and then analyze the role of intestinal microecology in the beneficial effects of exercise on CMDs, aiming at elucidating the gut-heart axis mechanisms of exercise mediated protective effect on CMDs, building avenues for the application of exercise in the management of CMDs.
心血管代谢疾病(CMDs)包括心血管和代谢功能障碍,以胰岛素抵抗、血脂异常、肝脂肪变性和炎症为特征,由于缺乏有效的治疗干预措施,其发病率和死亡率不断上升。近年来的研究表明,肠道微生物群及其自身代谢产物的变化可影响 CMD 的发生。有趣的是,肠道微生物群的组成和功能易受运动模式的影响,从而影响宿主体内的炎症、免疫和代谢反应。在这篇综述中,我们介绍了肠道微生态参与CMD发病和发展的关键机制,讨论了运动与肠道微生态之间的关系,然后分析了肠道微生态在运动对CMD的有益影响中的作用,旨在阐明运动介导的肠道-心脏轴对CMD的保护作用机制,为运动在CMD管理中的应用开辟途径。
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引用次数: 0
End-to-end donor screening and manufacturing controls: complementary quality-based strategies to minimize patient risk for donor-derived microbiome therapeutics. 端到端供体筛选和生产控制:基于质量的互补策略,最大限度地降低供体微生物组疗法的患者风险。
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-18 DOI: 10.1080/19490976.2024.2402550
Jason Goldsmith,Sarah Tomkovich,John G Auniņš,Barbara H McGovern,Jennifer C Mahoney,Brooke R Hasson,Christopher W J McChalicher,David S Ege
Advances in microbiome therapeutics have been motivated by a deeper understanding of the role that the gastrointestinal microbiome plays in human health and disease. The FDA approval of two stool-derived live biotherapeutic products (LBPs), REBYOTA® 150 mL enema (fecal microbiota, live-jslm; formerly RBX2660) and VOWST® oral capsules (fecal microbiota spores, live-brpk; formerly SER-109), for the prevention of recurrent CDI in adults following antibiotic treatment for recurrent CDI provides promise and insights for the development of LBPs for other diseases associated with microbiome dysfunction. Donor-derived products carry risk of disease transmission that must be mitigated through a robust donor screening program and downstream manufacturing controls. Most published recommendations for donor screening practices are prescriptive and do not include a systematic, risk-based approach for donor stool-derived products. A general framework for an end-to-end donor screening program is needed using risk management strategies for donor-derived microbiome therapeutic using a matrixed approach, combining the elements of donor screening with manufacturing controls that are designed to minimize risk to patients. A donor screening paradigm that incorporates medical history, physical examination, laboratory testing, and donor sample inspection are only the first steps in reducing risk of transmission of infectious agents. Manufacturing controls are the cornerstone of risk mitigation when screening unwittingly fails. Failure Mode and Effects Analysis (FMEA) can be used as a tool to assess for residual risk that requires further donor or manufacturing controls. Together, a well-reasoned donor program and manufacturing controls are complementary strategies that must be revisited and reexamined frequently with constant vigilance to mitigate risk to patients. In the spirit of full disclosure and informed consent, physicians should discuss any limitations in the donor screening and manufacturing processes with their patients prior to treatment with microbiome-based therapeutics.
对胃肠道微生物组在人类健康和疾病中所起作用的深入了解推动了微生物组疗法的发展。美国食品及药物管理局(FDA)批准了两种粪便来源的活生物治疗产品(LBPs),即 REBYOTA® 150 mL 灌肠剂(粪便微生物群,活-jslm;前身为 RBX2660)和 VOWST® 口服胶囊(粪便微生物群孢子,活-brpk;前身为 SER-109),用于预防成人在接受抗生素治疗后复发的 CDI,这为开发治疗其他与微生物群功能障碍相关疾病的 LBPs 提供了希望和启示。供体衍生产品存在疾病传播风险,必须通过健全的供体筛选计划和下游生产控制措施来降低风险。大多数已发布的供体筛查实践建议都是指令性的,并不包括针对供体粪便衍生产品的系统性、基于风险的方法。我们需要一个端到端供体筛选计划的总体框架,采用矩阵式方法对供体衍生的微生物组疗法进行风险管理策略,将供体筛选要素与旨在最大限度降低患者风险的生产控制相结合。包括病史、体格检查、实验室检测和供体样本检查在内的供体筛选模式只是降低传染源传播风险的第一步。当筛查无意中失败时,生产控制是降低风险的基石。失效模式及影响分析 (FMEA) 可用作评估残余风险的工具,需要对供体或生产进行进一步控制。合理的供体计划和生产控制是相辅相成的策略,必须经常重新审视和检查,时刻保持警惕,以降低患者面临的风险。本着充分披露和知情同意的精神,医生应在使用基于微生物组的疗法治疗前与患者讨论供体筛选和生产过程中的任何限制。
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引用次数: 0
Gut microbiota-derived butyrate selectively interferes with growth of carbapenem-resistant Escherichia coli based on their resistance mechanism. 根据耐碳青霉烯类大肠杆菌的耐药机制,源自肠道微生物群的丁酸盐可选择性地干扰耐碳青霉烯类大肠杆菌的生长。
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-18 DOI: 10.1080/19490976.2024.2397058
Eva Happ,Kora Schulze,Zinia Afrin,Sabrina Woltemate,Pia Görner,Stefan Ziesing,Dirk Schlüter,Robert Geffers,Volker Winstel,Marius Vital
We investigated consequences of resistance acquisition in Escherichia coli clinical isolates during anaerobic (continuous culture) growth and examined their sensitivity to butyrate, a hallmark metabolite of healthy gut microbiota. Strains were stratified based on carrying either a carbapenemase (CARB) or displaying porin malfunctioning (POR). POR displayed markedly altered growth efficiencies, lower membrane stability and increased sensitivity to butyrate compared with CARB. Major differences in global gene expression between the two groups during anaerobic growth were revealed involving increased expression of alternative substrate influx routes, the stringent response and iron acquisition together with lower expression of various stress response systems in POR. Longitudinal analyses during butyrate wash-in showed common responses for all strains as well as specific features of POR that displayed strong initial "overshoot" reactions affecting various stress responses that balanced out over time. Results were partly reproduced in a mutant strain verifying porin deficiencies as the major underlying mechanism for results observed in clinical isolates. Furthermore, direct competition experiments confirmed butyrate as key for amplifying fitness disadvantages based on porin malfunctioning. Results provide new (molecular) insights into ecological consequences of resistance acquisition and can assist in developing measures to prevent colonization and infection based on the underlying resistance mechanism.
我们研究了大肠埃希菌临床分离株在厌氧(连续培养)生长过程中获得耐药性的后果,并考察了它们对健康肠道微生物群的标志性代谢产物丁酸盐的敏感性。根据菌株是否携带碳青霉烯酶(CARB)或是否显示孔蛋白功能失常(POR)对其进行了分层。与 CARB 菌株相比,POR 菌株的生长效率明显改变,膜稳定性降低,对丁酸盐的敏感性增加。在厌氧生长过程中,两组之间的整体基因表达存在重大差异,其中 POR 的替代底物流入途径、严格反应和铁获取的表达增加,而各种应激反应系统的表达较低。在丁酸盐冲洗过程中进行的纵向分析表明,所有菌株都有共同的反应,而 POR 则有一些特殊的特征,表现出强烈的初始 "过冲 "反应,影响了各种应激反应,但随着时间的推移逐渐趋于平衡。结果在一个突变菌株中得到了部分重现,验证了孔蛋白缺陷是临床分离物中观察到的结果的主要基本机制。此外,直接竞争实验证实,丁酸盐是扩大基于孔蛋白功能失常的适应性劣势的关键。研究结果为获得抗药性的生态后果提供了新的(分子)见解,有助于根据潜在的抗药性机制制定预防定植和感染的措施。
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引用次数: 0
Molecular serotyping of diarrheagenic Escherichia coli with a MeltArray assay reveals distinct correlation between serotype and pathotype. 利用熔融阵列检测法对致泻性大肠埃希菌进行分子血清分型,发现血清型与病理型之间存在明显的相关性。
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-18 DOI: 10.1080/19490976.2024.2401944
Chen Du,Yiqun Liao,Congcong Ding,Jiayu Huang,Shujuan Zhou,Yiyan Xu,Zhaohui Yang,Xiaolu Shi,Yinghui Li,Min Jiang,Le Zuo,Minxu Li,Shengzhe Bian,Na Xiao,Liqiang Li,Ye Xu,Qinghua Hu,Qingge Li
Diarrheagenic Escherichia coli serotypes are associated with various clinical syndromes, yet the precise correlation between serotype and pathotype remains unclear. A major barrier to such studies is the reliance on antisera-based serotyping, which is culture-dependent, low-throughput, and cost-ineffective. We have established a highly multiplex PCR-based serotyping assay, termed the MeltArray E. coli serotyping (EST) assay, capable of identifying 163 O-antigen-encoding genes and 53 H-antigen-encoding genes of E. coli. The assay successfully identified serotypes directly from both simulated and real fecal samples, as demonstrated through spike-in validation experiments and a retrospective study. In a multi-province study involving 637 E. coli strains, it revealed that the five major diarrheagenic pathotypes have distinct serotype compositions. Notably, it differentiated 257 Shigella isolates into four major Shigella species, distinguishing them from enteroinvasive E. coli based on their distinct serotype profiles. The assay's universality was further corroborated by in silico analysis of whole-genome sequences from the EnteroBase. We conclude that the MeltArray EST assay represents a paradigm-shifting tool for molecular serotyping of E. coli, with potential routine applications for comprehensive serotype analysis, disease diagnosis, and outbreak detection.
腹泻性大肠埃希菌血清型与各种临床综合征有关,但血清型与病理型之间的确切相关性仍不清楚。此类研究的一个主要障碍是依赖抗血清进行血清分型,这种方法依赖培养、通量低、成本效益差。我们建立了一种基于 PCR 的高度多重血清分型检测方法,称为 MeltArray 大肠杆菌血清分型(EST)检测方法,能够鉴定大肠杆菌的 163 个 O 抗原编码基因和 53 个 H 抗原编码基因。通过尖峰验证实验和一项回顾性研究,该测定法成功地从模拟和真实粪便样本中直接鉴定出血清型。在一项涉及 637 株大肠杆菌的多省研究中,它揭示了五种主要腹泻致病型具有不同的血清型组成。值得注意的是,它将 257 株志贺氏菌分离物分为四大志贺氏菌种,并根据其不同的血清型特征将它们与肠道入侵性大肠杆菌区分开来。对 EnteroBase 中的全基因组序列进行的硅分析进一步证实了该检测方法的普遍性。我们的结论是,MeltArray EST 检测法是大肠杆菌分子血清型分型的一种范式转换工具,有望常规应用于全面的血清型分析、疾病诊断和疫情检测。
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引用次数: 0
Empowering probiotics with high xanthine transport for effective hyperuricemia management. 增强益生菌的高黄嘌呤转运能力,有效控制高尿酸血症。
IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-17 DOI: 10.1080/19490976.2024.2399213
Zhen-Ping Zou,Ju-Ling Li,Yi-Fan Zhang,Ying Zhou,Bang-Ce Ye
Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.
高尿酸血症是一种常见的代谢性疾病,容易引发各种并发症。治疗高尿酸血症的传统药物疗法往往会产生显著的不良反应,给临床带来巨大挑战。因此,当务之急是开发新型、安全、有效的高尿酸血症预防和治疗策略。在这里,我们开发了一种益生菌大肠杆菌 Nissle 1917 菌株,命名为 YES301,它含有合理设计的黄嘌呤导入因子 XanQ,能有效吸收黄嘌呤和次黄嘌呤,从而降低血清尿酸浓度,并改善小鼠高尿酸血症模型的肾功能损伤。重要的是,YES301 的疗效与传统降尿酸药物别嘌醇相当,而且不良反应更少,生物安全性更高。这些发现凸显了工程益生菌通过降低肠道嘌呤水平治疗高尿酸血症的巨大潜力。
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引用次数: 0
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