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Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside

《医学前沿（英文）》 2022年第16卷第5期页码 686-700 doi: 10.1007/s11684-022-0957-7

摘要： Systemic lupus erythematosus (SLE) is a complicated autoimmune disease affecting multiple systems and organs. It is highly heterogeneous, and it preferentially affects women at childbearing age, causing worldwide social burden. The pathogenesis of SLE mostly involves genetic predisposition, epigenetic dysregulation, overactivation of the immune system, and environment factors. Human microbiome, which is mostly composed of microbiota colonized in the gut, skin, and oral cavity, provides a natural microbiome barrier against environmental risks. The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases. However, the role of microbiota in autoimmunity remains largely unknown until recently, when the technological and methodological progress facilitates further microbiota research in SLE. In this review, the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.

关键词： systemic lupus erythematosus microbiota biotherapy

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Gut microbiota and its implications in small bowel transplantation

null

《医学前沿（英文）》 2018年第12卷第3期页码 239-248 doi: 10.1007/s11684-018-0617-0

摘要：

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host–microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

关键词： gut microbiota small bowel transplantation acute rejection chronic rejection mucosal immunity biomarker microbiota-targeted therapy

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Altered intestinal microbiota associated with colorectal cancer

Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia

《医学前沿（英文）》 2019年第13卷第4期页码 461-470 doi: 10.1007/s11684-019-0695-7

摘要： The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal–luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in which is a butyrate-producing genera of bacteria, and a significant increase in in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identiﬁed. The observed abundance of bacterial species belonging to and may serve as a promising biomarker for the early detection of CRC.

关键词： colorectal cancer (CRC) gut microbiota intestinal Eubacterium Devosia

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Clinical factors associated with composition of lung microbiota and important taxa predicting clinical

《医学前沿（英文）》 2022年第16卷第3期页码 389-402 doi: 10.1007/s11684-021-0856-3

摘要： Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R²=0.033; P=0.018), followed by acute kidney injury (AKI; R²=0.032; P=0.011) and plasma MIP-1β level (R²=0.027; P=0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients’ lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

关键词： severe community-acquired pneumonia lung microbiota clinical improvements 7-category ordinal scale Prevotellaceae

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通过调控肠道菌群治疗慢性疾病

洪斌, 蒋建东

《工程（英文）》 2022年第18卷第11期页码 17-20 doi: 10.1016/j.eng.2021.08.015

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Untargeted metabolomic analysis of pregnant women exposure to perfluorooctanoic acid at different degrees

《环境科学与工程前沿（英文）》 2023年第17卷第3期 doi: 10.1007/s11783-023-1628-x

摘要：

● Metabolome can distinguish pregnant women exposure to PFOA at different degrees.

关键词： Perfluorooctanoic acid Exposure Pregnant women Metabolomic GSH Microbiota metabolism

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微生态如何影响人体健康？

李兰娟

《工程（英文）》 2017年第3卷第1期页码 1-1 doi: 10.1016/J.ENG.2017.01.021

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肠道菌群与肿瘤发生及肝病

吕桂帅, 程宁涛, 王红阳

《工程（英文）》 2017年第3卷第1期页码 110-114 doi: 10.1016/J.ENG.2017.01.017

摘要：

一个多世纪以前，科学家们就首次发现了肿瘤区域中细菌的存在。但是，微生物在肿瘤发生中的作用近年来才被认识到。近几十年来，与肠道菌群失调相关的疾病代表了全世界最严重的一些公共卫生问题。大量的流行病学研究表明，肠道菌群与某些常见肿瘤密切相关。然而，肠道菌群与肿瘤相关联的具体分子机制仍不明确。研究表明，肠道菌群的改变有助于确定肝癌、酒精相关肝病、非酒精性脂肪肝和肝硬化的发生和发展。鉴于益生菌是一种可通过调节免疫系统促进人类健康的药物，其可能会为肝细胞癌(HCC) 和非酒精性脂肪肝的治疗提供新方向。本文总结了肠道菌群在肿瘤及肝病中的研究进展，综述了肠道菌群与肿瘤和肝病之间的关系。此外，考虑到细菌内稳态的重要性，我们也对益生菌进行了概述，旨在为相关疾病的治疗提供指导。

关键词：肠道菌群稳态失调肿瘤发生肝细胞癌非酒精性脂肪性肝病

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从农场到微生物工程：微生态与过敏性疾病

Dominique Angèle Vuitton, Jean-Charles Dalphin

《工程（英文）》 2017年第3卷第1期页码 98-109 doi: 10.1016/J.ENG.2017.01.019

摘要：

第二次世界大战之后，IgE 依赖性过敏性疾病的发生呈稳步上升趋势，在人类发展史上，这种现象是很罕见的。许多大规模横断面研究、纵向队列研究及基础实验性研究均指出，在生活方式及生活环境的重大演变过程中人类的一些与过敏相关的“保护性因素”正逐渐消失。其中被广泛认可的观念是：肠道微生态在免疫调节方面扮演着重要角色。本文综述了暴露在不同微生物组成的农场环境对过敏性疾病的保护作用。此外，传统生活环境中的微生物如何促进儿童免疫系统的正常发育，以及此种相互作用在现代生活方式下的不可逆性缺失同样被阐明。“农场效应”的保护作用主要包括：母亲怀孕期间或婴儿期接触动物、谷仓、马厩，饮用未加工的牛奶和其他奶制品。除农场环境中的微生物总量之外，微生物的生物多样性似乎对于这种保护也至关重要，这可能归因于农场环境对机体肠道菌群生物多样性的贡献。过敏性疾病专科医生和儿科医生临床应用传统益生菌(如乳杆菌和双岐杆菌)对过敏性疾病的预防作用并未达到满意的预期效果。小鼠呼吸道过敏性疾病模型研究表明，牛棚中存在着对过敏性疾病起重要预防作用的微生物，如鲁氏不动杆菌(A.lwoffii) F78、乳酸乳球菌(L. lactis) G121 和松鼠葡萄球菌(S.sciuri)W620。然而，在对农场环境的卓有成效的研究基础上，研发新一代益生菌仍需要微生物学家、免疫学家和生物工程师以及儿科医生、过敏性疾病专科医生、临床试验专家和伦理委员会之间的密切合作。

关键词：过敏农场生物多样性免疫调节微生态转化研究

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Structural shifts in the intestinal microbiota of rats treated with cyclosporine A after orthotropic

Junjun Jia, Xinyao Tian, Jianwen Jiang, Zhigang Ren, Haifeng Lu, Ning He, Haiyang Xie, Lin Zhou, Shusen Zheng

《医学前沿（英文）》 2019年第13卷第4期页码 451-460 doi: 10.1007/s11684-018-0675-3

摘要： Understanding the effect of immunosuppressive agents on intestinal microbiota is important to reduce the mortality and morbidity from orthotopic liver transplantation (OLT). We investigated the relationship between the commonly used immunosuppressive agent cyclosporine A (CSA) and the intestinal microbial variation in an OLT model. The rat samples were divided as follows: (1) N group (normal control); (2) I group (isograft LT, Brown Norway [BN] rat to BN); (3) R group (allograft LT, Lewis to BN rat); and (4) CSA group (R group treated with CSA). The intestinal microbiota was assayed by denaturing gradient gel electrophoresis profiles and by using real-time polymerase chain reaction. The liver histopathology and the alanine/aspartate aminotransferase ratio after LT were both ameliorated by CSA. In the CSA group, the numbers of rDNA gene copies of cluster I, cluster XIV, and Enterobacteriaceae decreased, whereas those of increased compared with the R group. Cluster analysis indicated that the samples from the N, I, and CSA groups were clustered, whereas the other clusters contained the samples from the R group. Hence, CSA ameliorates hepatic graft injury and partially restores gut microbiota following LT, and these may benefit hepatic graft rejection.

关键词： microbial community liver transplantation immunosuppressive agents cyclosporine A

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人体微生态与健康

王保红, 姚铭飞, 吕龙贤, 凌宗欣, 李兰娟

《工程（英文）》 2017年第3卷第1期页码 71-82 doi: 10.1016/J.ENG.2017.01.008

摘要：

数以万亿计的微生物寄生于人体表面和体内，并与人类起演变多种环境因素可影响胃肠道微生的平衡，这些改变与人体健康和疾病密切相关本文重点关注人体微生与宿主之间的相互作用，总体概括微生物在人体基本生命过程中以及主要疾病中起的作用，如感染性疾病肝脏疾病胃肠道肿瘤、代谢疾病呼吸系统疾病精神或心理疾病和自身免疫疾病等。我们还综述了微生物研究相关术的重要进展，如DNA 测序、代谢组学和基于计算生物信息学的蛋白质组学目前对人类微生态的研究已经更加复杂和全面建议研究应更多关注–宿主微生物的相互作用和因果关系，这有助于我们更好地了解肠道微生物在人类健康和疾病中的作用，并为临床实践提供新的治疗靶点和方法。

关键词：微生物健康传染病肝病胃肠道恶性肿瘤代谢紊乱微生物技术益生菌

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Arbuscular mycorrhizal associations and the major regulators

Li XUE, Ertao WANG

《农业科学与工程前沿（英文）》 2020年第7卷第3期页码 296-306 doi: 10.15302/J-FASE-2020347

摘要：

Plants growing in natural soils encounter diverse biotic and abiotic stresses and have adapted with sophisticated strategies to deal with complex environments such as changing root system structure, evoking biochemical responses and recruiting microbial partners. Under selection pressure, plants and their associated microorganisms assemble into a functional entity known as a holobiont. The commonest cooperative interaction is between plant roots and arbuscular mycorrhizal (AM) fungi. About 80% of terrestrial plants can form AM symbiosis with the ancient phylum Glomeromycota. A very large network of extraradical and intraradical mycelium of AM fungi connects the underground biota and the nearby carbon and nutrient fluxes. Here, we discuss recent progress on the regulators of AM associations with plants, AM fungi and their surrounding environments, and explore further mechanistic insights.

关键词： AM symbiosis signal regulators nutrients phosphate microbiota

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生命早期微生物群的发育与人类的健康和疾病 Review

吕晗莹, 张立将, 韩玉秋, 伍莉, 王保红

《工程（英文）》 2022年第12卷第5期页码 101-114 doi: 10.1016/j.eng.2020.12.014

摘要：

人类微生物群在生命早期的定植对健康具有长期的影响。最初肠道微生物群的状态决定了人类从婴儿期到成年期的生长发育，因此是人类长期发育的一个关键窗口期。本文旨在总结生命早期共生肠道微生物群的最新发现及其在代谢、过敏和自身免疫疾病相关的疾病（包括肥胖症、糖尿病、过敏性疾病、自闭症、炎症性肠病和发育迟缓）中的重要作用。本文讨论了肠道微生物群发育过程和塑造肠道微生物群的各种因素，以及肠道微生物群在生命早期建立过程中与宿主生理系统之间的串扰（尤其是肠道免疫发育和稳态，以及神经发育过程中的中枢神经系统），以破译与生命早期肠道微生物组相关的疾病机制。此外，还考察了以微生物群为靶向的治疗方法，并显示出这些方法对于上述疾病具有一定的治疗潜力。肠道微生物组正确的成熟过程取决于遗传、营养和环境因素，必须详细检查，以监测健康的肠道微生物组发育，并通过新型益生菌或粪便微生物群移植等方法进行干预，尽可能以此纠正错误的发育过程。

关键词：微生物儿科疾病益生菌神经发育肠道免疫系统发育

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Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy

《医学前沿（英文）》 2022年第16卷第3期页码 307-321 doi: 10.1007/s11684-022-0927-0

摘要： The discovery of immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4, has played an important role in the development of cancer immunotherapy. However, immune-related adverse events often occur because of the enhanced immune response enabled by these agents. Antibiotics are widely applied in clinical treatment, and they are inevitably used in combination with immune checkpoint inhibitors. Clinical practice has revealed that antibiotics can weaken the therapeutic response to immune checkpoint inhibitors. Studies have shown that the gut microbiota is essential for the interaction between immune checkpoint inhibitors and antibiotics, although the exact mechanisms remain unclear. This review focuses on the interactions between immune checkpoint inhibitors and antibiotics, with an in-depth discussion about the mechanisms and therapeutic potential of modulating gut microbiota, as well as other new combination strategies.

关键词： tumor immunotherapy immune checkpoint inhibitor antibiotics gut microbiota drug–drug interaction

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Calorie restriction and its impact on gut microbial composition and global metabolism

Xiaojiao Zheng, Shouli Wang, Wei Jia

《医学前沿（英文）》 2018年第12卷第6期页码 634-644 doi: 10.1007/s11684-018-0670-8

摘要：

Calorie restriction (CR) is a dietary regimen that reduces calorie intake without incurring malnutrition or a reduction in essential nutrients. It has long been recognized as a natural strategy for promoting health, extending longevity, and prevents the development of metabolic and age-related diseases. In the present review, we focus on the general effect of CR on gut microbiota composition and global metabolism. We also propose mechanisms for its beneficial effect. Results showed that probiotic and butyrate-producing microbes increased their relative abundance, whereas proinflammatory strains exhibited suppressed relative abundance following CR. Analyses of the gut microbial and host metabolisms revealed that most host microbial co-metabolites were changed due to CR. Examples of dramatic CR-induced changes in host metabolism included a decrease in the rate of lipid biosynthesis and an increase in the rates of fatty acid catabolism, β-oxidation, glycogenolysis, and gluconeogenesis. The observed phenotypes and the further verification of the direct link between gut microbiota and metabolome may benefit patients that are at risk for developing metabolic disease. Thus, improved gut microbiota composition and metabolome are potential biomarkers for determining the effectiveness of dietary interventions for age-related and metabolic diseases.

关键词： caloric restriction gut microbiota metabolome