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Integrated analysis of gut microbiome and host immune responses in COVID-19

《医学前沿（英文）》 2022年 第16卷 第2期   页码 263-275 doi: 10.1007/s11684-022-0921-6

摘要： Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词： COVID-19     SARS-COV-2     gut microbiome     immune response    

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Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

《工程（英文）》 doi: 10.1016/j.eng.2023.06.007

摘要： Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host–microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1ΔIEC) and Paneth cell (PC; Axin1ΔPC) to compare with control (Axin1LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1ΔIEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium-induced colitis in vivo. Axin1ΔIEC and Axin1ΔPC mice became more susceptible to dextran sulfate sodium (DSS)-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1Loxp mice. However, the intestinal proliferative cells in Axin1ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1ΔIEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

关键词： Axin1     Bacteria     Microbiome inflammation     Inflammatory bowel disease     Immunity     Microbiome     Paneth cells     Akkermansia muciniphila     Wnt    

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宿主微生物组内的基因组突变——适应性进化或净化选择 Review

张家超, Rob Knight

《工程（英文）》 2023年 第20卷 第1期   页码 96-102 doi: 10.1016/j.eng.2021.11.018

摘要：

二代测序技术转变了人们评估宿主相关微生物区系和微生物组的分类组成功能的能力。未来10 年将会开展更多的人类微生物组研究，特别是那些探索微生物组内基因组突变的研究。本文聚焦于微生物组内菌株之间的共同进化，塑造了宿主肠道微生物种内和种间的菌株水平多样性。还探讨了微生物基因组突变与常见代谢疾病之间的关联，以及病原体和益生菌在入侵和定植过程中的适应性进化。最后，讨论了注释和分析微生物基因组突变方法和算法的研究进展。

关键词： 肠道菌群     基因组突变     适应性进化     净化选择     单核苷酸变异    

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肠道微生态——探索中药临床疗效的新思路 Review

陆艳蒙, 谢娇娇, 彭聪高, 王保红, 王恺岑, 李兰娟

《工程（英文）》 2019年 第5卷 第1期   页码 40-49 doi: 10.1016/j.eng.2018.11.013

摘要：

自古以来，中药在疾病预防、症状缓解和健康改善等方面发挥了重要作用。然而，复杂的成分和尚未明确的机制阻碍了中药的广泛推广和应用。越来越多的研究表明，和人体健康息息相关的肠道微生态与中药的疗效有关，因此从肠道微生态的角度去探索中药可能是打开中药奥秘的金钥匙。肠道菌群主要通过以下4个生理途径中发挥作用：参与宿主代谢、调节系统免疫、维持胃肠道稳态以及影响脑功能和宿主行为。本文回顾了中药与慢性肝病、溃疡性结肠炎、肥胖和2型糖尿病等疾病之间的联系，从肠道微生态的角度阐明其潜在的机制。未来，我们需要进一步的研究和更完善的实验设计，以揭示中药与肠道菌群之间相互作用的具体机制，并为中药的创新研究提供新的思路。

关键词： 中药     肠道菌群     脂肪肝     溃疡性结肠炎     肥胖     糖尿病    

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Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

《医学前沿（英文）》 doi: 10.1007/s11684-023-1029-3

摘要： Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

关键词： tumor prognosis molecular     Microbiome subsets determine     center analysis microbiome     transcriptome data    

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Gut microbial balance and liver transplantation: alteration, management, and prediction

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 123-129 doi: 10.1007/s11684-017-0563-2

摘要：

Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

关键词： gut microbial balance     liver transplantation     ischemia–reperfusion     acute rejection    

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Understanding building-occupant-microbiome interactions toward healthy built environments: A review

Shuai Li, Zhiyao Yang, Da Hu, Liu Cao, Qiang He

《环境科学与工程前沿（英文）》 2021年 第15卷 第4期 doi: 10.1007/s11783-020-1357-3

摘要： Abstract • The built environment, occupants, and microbiomes constitute an integrated ecosystem. • This review summarizes research progress which has focused primarily on microbiomes. • Critical research needs include studying impacts of occupant behaviors on microbiomes. Built environments, occupants, and microbiomes constitute a system of ecosystems with extensive interactions that impact one another. Understanding the interactions between these systems is essential to develop strategies for effective management of the built environment and its inhabitants to enhance public health and well-being. Numerous studies have been conducted to characterize the microbiomes of the built environment. This review summarizes current progress in understanding the interactions between attributes of built environments and occupant behaviors that shape the structure and dynamics of indoor microbial communities. In addition, this review also discusses the challenges and future research needs in the field of microbiomes of the built environment that necessitate research beyond the basic characterization of microbiomes in order to gain an understanding of the causal mechanisms between the built environment, occupants, and microbiomes, which will provide a knowledge base for the development of transformative intervention strategies toward healthy built environments. The pressing need to control the transmission of SARS-CoV-2 in indoor environments highlights the urgency and significance of understanding the complex interactions between the built environment, occupants, and microbiomes, which is the focus of this review.

关键词： Microbiome     Built Environment     Occupant     Health    

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Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

《环境科学与工程前沿（英文）》 2022年 第16卷 第5期 doi: 10.1007/s11783-022-1543-6

摘要：

● Riverine microbiomes exhibited hyperlocal variation within a single transect.

关键词： Microbiome     Freshwater     Taxon accumulation curve     Community assembly    

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Human microbiome and prostate cancer development: current insights into the prevention and treatment

Solmaz Ohadian Moghadam, Seyed Ali Momeni

《医学前沿（英文）》 2021年 第15卷 第1期   页码 11-32 doi: 10.1007/s11684-019-0731-7

摘要： The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.

关键词： microbiome     prostate cancer     prevention     treatment     molecular pathological epidemiology (MPE)     biomarker    

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Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota

Ruiting Han, Junli Ma, Houkai Li

《医学前沿（英文）》 2018年 第12卷 第6期   页码 645-657 doi: 10.1007/s11684-018-0645-9

摘要： Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical “Two-hit” theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a “metabolic organ” that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.

关键词： gut microbiota     NAFLD     obesity     insulin resistance     bile acids     probiotic    

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Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

《环境科学与工程前沿（英文）》 2022年 第16卷 第6期 doi: 10.1007/s11783-022-1560-5

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肝脏移植术后糖尿病患者肠道微生物组的变化 Article

凌琪, 韩玉秋, 马越, 王晓森, 朱铮, 王靖宇, 曹佳莹, 林笑含, 王军, 王保红

《工程（英文）》 2023年 第31卷 第12期   页码 98-111 doi: 10.1016/j.eng.2023.09.006

摘要：

移植后糖尿病（PTDM）会增加肝移植（LT）受者移植失败和死亡的风险。实验研究表明免疫抑制性他克莫司（TAC）介导的肠道生态失调可能导致血糖紊乱，但仍尚未见相关临床研究报道。 因此，本研究通过高通量鸟枪法宏基因组测序和代谢组学分析相结合的方法，对PTDM和非PTDM的肝脏移植受者队列中的肠道微生物组（IM）进行了表征，并破译了IM、TAC剂量和PTDM之间的潜在关联。 通过与非 PTDM 和经典II型糖尿病（T2DM）进行对比分析，确定了PTDM患者的肠道微生物组代表性特征为：变形菌门富集和拟杆菌门减少。有趣的是，与改变的微生物代谢产物相一致，这些微生物在PTDM患者中的丰都变化与TAC的剂量显著关联。 具体来说，与低TAC 谷浓度（< 5 ng∙mL–1） 的移植受体相比较，高 TAC 谷浓度（> 5 ng∙mL–1）移植受者中的有益微生物水平被显著降低；同时，通过检测粪便代谢物发现其中参与α-亚麻酸和花生四烯酸-这些降低糖尿病发生的有益代谢物的显著降低。更进一步，这些微生物标签分子的变化与移植受者的血糖紊乱程度显著有关。 总之，PTDM患者的粪便微生物组和代谢组发生了显著变化，且与 TAC 剂量相关。 这项研究是首个探索PTDM患者的细菌分类学组成变化和细菌基因功能变化，以更好地理解IM对PTDM的影响。

关键词： 移植后糖尿病     他克莫司     红基因组学     代谢组学    

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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    

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Comparative analysis of impact of human occupancy on indoor microbiomes

《环境科学与工程前沿（英文）》 2021年 第15卷 第5期 doi: 10.1007/s11783-020-1383-1

摘要：

• Exposure to indoor microbiomes is a public health concern in educational facilities.

关键词： Built environment     Indoor microbiome     Occupant     Building     Sequencing    

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ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis

《医学前沿（英文）》   页码 972-992 doi: 10.1007/s11684-023-0990-1

摘要： Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H2S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

关键词： inflammatory bowel disease     ADT-OH     intestinal permeability     gut microbiota    

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标题 作者 时间 类型 操作

Integrated analysis of gut microbiome and host immune responses in COVID-19

期刊论文

Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

期刊论文

宿主微生物组内的基因组突变——适应性进化或净化选择

张家超, Rob Knight

期刊论文

肠道微生态——探索中药临床疗效的新思路

陆艳蒙, 谢娇娇, 彭聪高, 王保红, 王恺岑, 李兰娟

期刊论文

Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

期刊论文

Gut microbial balance and liver transplantation: alteration, management, and prediction

null

期刊论文

Understanding building-occupant-microbiome interactions toward healthy built environments: A review

Shuai Li, Zhiyao Yang, Da Hu, Liu Cao, Qiang He

期刊论文

Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

期刊论文

Human microbiome and prostate cancer development: current insights into the prevention and treatment

Solmaz Ohadian Moghadam, Seyed Ali Momeni

期刊论文

Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota

Ruiting Han, Junli Ma, Houkai Li

期刊论文

Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

期刊论文

肝脏移植术后糖尿病患者肠道微生物组的变化

凌琪, 韩玉秋, 马越, 王晓森, 朱铮, 王靖宇, 曹佳莹, 林笑含, 王军, 王保红

期刊论文

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

Xiaojiao Zheng, Shouli Wang, Wei Jia

期刊论文

Comparative analysis of impact of human occupancy on indoor microbiomes

期刊论文

ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis

期刊论文