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Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives

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Frontiers of Medicine 2022年第5期16卷 667-685页

作者： yuqiu han Lanjuan Li Baohong Wang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China

Nonalcoholic fatty liver disease(NAFLD)is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer.Akkermansia muciniphila(A.muciniphila)is a next-generation probiotic that has been reported to improve metabolic disorders.Emerging evidence indicates the therapeutic potential of A.muciniphila for NAFLD,especially in the inflammatory stage,nonalcoholic steatohepatitis.Here,the current knowledge on the role of A.muciniphila in the progression of NAFLD was summarized.A.muciniphila abundancy is decreased in animals and humans with NAFLD.The recovery of A.muciniphila presented benefits in preventing hepatic fat accumulation and inflammation in NAFLD.The details of how microbes regulate hepatic immunity and lipid accumulation in NAFLD were further discussed.The modulation mechanisms by which A.muciniphila acts to improve hepatic inflammation are mainly attributed to the alleviation of inflammatory cytokines and LPS signals and the downregulation of microbiota-related innate immune cells(such as macrophages).This review provides insights into the roles of A.muciniphila in NAFLD,thereby providing a blueprint to facilitate clinical therapeutic applications.

关键词： Akkermansia muciniphila NAFLD NASH steatosis inflammation

The Development of Early Life Microbiota in Human Health and Disease

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Engineering 2022年第5期8卷 101-114页

作者： hanying Lv Lijiang Zhang yuqiu han Li Wu Baohong Wang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China Center of Safety Evaluation Hangzhou Medical College(Zhejiang Academy of Medical Sciences)Hangzhou 310053China Research Units of Infectious Disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China

The colonization of the human microbiota in early life has long-lasting health implications.The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood,and thus represents a crucial window in our long-term development.This review aims to summarize the latest findings on the symbiotic gut microbiota early in life and its vital role in metabolic-,allergic-,and auto-immune-disorder-related diseases,including obesity,diabetes,allergy,autism,inflammatory bowel disease,and stunting.It discusses the development process and various factors shaping the gut micro-biota,as well as the crosstalk between the gut microbiota and the host’s physiological systems(especially intestinal immune development and homeostasis,and the central nervous system in the course of neu-rodevelopment),during the early life establishment of the gut microbiota,in order to decipher the mech-anisms of diseases associated with the intestinal microbiome of early life.In addition,it examines microbiota-targeted therapeutic methods that show promising effects in treating these diseases.The true process of gut microbiome maturation,which depends on genetics,nutrition,and environmental factors,must be scrutinized in order to monitor healthy gut microbiome development and potentially correct unwanted courses by means of intervention via methods such as novel probiotics or fecal microbiota transplantation.

关键词： Microbiota Pediatric diseases Probiotics Neurodevelopment Intestinal immune development

Gut Microbiota-Controlled Tryptophan Metabolism Improves D-Gal/LPS-Induced Acute Liver Failure in C57BL/6 Mice

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Engineering 2022年第7期8卷 134-146页

作者： Zhipeng Zheng Li Wu yuqiu han Jun Chen Shuai Zhu Yuanyuan Yao Baohong Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China

Acute liver failure(ALF)has an abrupt onset with a frequently fatal outcome.Previous studies have found that oral antibiotics prevent drug-induced liver injury in animal experiments,indicating that the gut microbiota plays a critical role in the pathophysiological process.However,the underlying mechanism has not been fully understood.This study explored the comprehensive role of the gut microbiota in ALF using multi-omics.A cocktail of broad-spectrum antibiotics(Abx)pretreatment by gavage for four weeks improved the survival of D-(+)-galactosamine hydrochloride(D-Gal)/lipopolysaccharide(LPS)-induced ALF in C57BL/6 mice.RNA sequencing showed that inflammatory responses were inhibited and metabolic pathways were upregulated in the liver of Abx-treated ALF mice.The 16S rRNA gene sequencing revealed that Abx reshaped the composition and function of the gut microbiota,with an increased proportion of tryptophan(Trp)metabolism.In addition,global metabolic profiling by ultraperformance liquid chromatography–mass spectrometry(UPLC–MS)indicated that the gut microbiota post-Abx intervention reduced Trp excretion,liberated more Trp to the host,and enhanced the kynurenine(Kyn)pathway with increased production of Kyn.As an endogenous aryl hydrocarbon receptor(AhR)ligand,Kyn has anti-inflammatory and immunosuppressive effects.Furthermore,AhR-targeted treatments affected the outcome of ALF mice with or without Abx pretreatment,indicating that AhR directly regulated susceptibility to ALF,at least in part.This study demonstrates that the gut microbiota-dependent control of the Trp metabolism could regulate host susceptibility to ALF by modulating the activity of AhR,and thus provides a promising target for better management of ALF.

关键词： Gut microbiota Antibiotic Tryptophan Kynurenine Aryl hydrocarbon receptor Acute liver failure

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肝脏移植术后糖尿病患者肠道微生物组的变化

Engineering 2023年第12期31卷 98-111页

作者： Qi Ling yuqiu han Yue Ma Xiaosen Wang Zheng Zhu Jingyu Wang Jiaying Cao Lin Xiaohan Jun Wang Baohong Wang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China Department of Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Lab of Combined Multi-Organ Transplantation Ministry of Public HealthHangzhou 310003China CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Shandong First Medical University&Shandong Academy of Medical Sciences Jinan 250117China Research Units of Infectious Disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China

Post-transplant diabetes mellitus(PTDM)increases the risk of graft failure and death in liver transplant(LT)recipients.Experimental studies have indicated that enteric dysbiosis mediated by immunosuppressive tacrolimus(TAC)could contribute to glucose disorders,but no data on human recipients with PTDM have been reported.Here,by combining high-throughput shotgun metagenomics sequencing and metabolomics profiling,we characterized the intestinal microbiome(IM)in LT recipient cohort with or without PTDM and deciphered the potential relationship among IM,TAC dosage,and diabetes.By comparing with both non-PTDM and classical type 2 diabetes mellitus(T2DM),we identified microbial signatures of PTDM,which was characterized by the enriched Proteobacteria and decreased Bacteroidetes.Additionally,the altered microbes,as well as the microbial metabolomics,correlated with the dosage of TAC.Specifically,the levels of beneficial microbes associated with PTDM were lowered in recipients with the high TAC trough concentrations(>5 ng·mL^(-1))than those with low ones(<5 ng·mL^(-1)),which was accompanied by reduced faecal metabolites involved in the biosynthesis of a-linolenic acid and arachidonic acid-lowering factors of developing T2DM.Moreover,these microbial signatures linked with the extent of glucose disorders in LT recipients.In summary,the faecal microbiome and metabolome differed between PTDM and non-PTDM patients,which were linked with TAC dosage.This study was the first to explore taxonomic alterations and bacterial gene functions to better understand the contribution of the IM to PTDM.

关键词： Post-transplant diabetes mellitus Tacrolimus Metagenomics Metabolomics

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders in mice

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Frontiers of Medicine 2019年第4期13卷 471-481页

作者： yuqiu han Xiangyang Jiang Qi Ling Li Wu Pin Wu Ruiqi Tang Xiaowei Xu Meifang Yang Lijiang Zhang Weiwei Zhu Baohong Wang Lanjuan Li National Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Division of Hepatobiliary and Pancreatic Surgery Department of Surgery the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Division of Throat Surgery the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Center of Safety Evaluation Zhejiang Academy of Medical Sciences Hangzhou 310053 China

Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Copyococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

关键词： antibiotics tacrolimus glucose disorders microbiome

大鼠肠道平滑肌胶原条带构建及周期性拉伸培养的体外评价

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中国组织工程研究 2024年第35期28卷 5630-5635页

作者：于朋鑫韩禹秋郭丽娜王秀丽大连医科大学辽宁省大连市116000

背景:肠道平滑肌层是肠道管壁结构的重要组成部分,在组织工程化肠道的仿生构建中备受关注。目的:探索周期性机械拉伸对胶原条带内肠道平滑肌细胞生长活性以及功能基因表达的影响。方法:以自制鼠尾胶原为支架,以大鼠原代肠道平滑肌细胞... 详细信息

背景:肠道平滑肌层是肠道管壁结构的重要组成部分,在组织工程化肠道的仿生构建中备受关注。目的:探索周期性机械拉伸对胶原条带内肠道平滑肌细胞生长活性以及功能基因表达的影响。方法:以自制鼠尾胶原为支架,以大鼠原代肠道平滑肌细胞为种子细胞,同时结合自主设计的胶原条带拉伸培养装置,构建肠道平滑肌细胞胶原条带培养体系,采用Eth D-1/Calcein-AM细胞活性染色、洋红染色、细胞骨架-Ki67免疫荧光染色观察细胞的生长活性与增殖情况,定量RT-PCR检测desmin、α-sma、vimentin功能基因的表达。结果与结论:(1)成功构建肠道平滑肌细胞胶原条带培养体系,条带内肠道平滑肌细胞具有良好的细胞活性;(2)与静态培养相比,周期性拉伸动态培养条件下Ki67阳性表达的细胞数量增多且显著高表达标志性基因desmin、α-sma、vimentin(P<0.001);(3)结果表明:机械力学刺激有利于肠道平滑肌细胞在体外培养过程中维持生长状态,并促进其功能性分化。

关键词：组织工程肠道平滑肌胶原条带动态拉伸胶原支架三维培养

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汉代军戎服饰的形制与功用

中国艺术 2024年第3期 96-103页

作者：吉嘉敏蒋玉秋北京服装学院美术学院

本文采用文献考证与实物研究相结合的二重证据法对汉代军戎服饰的形制与功用进行考证、探究。通过观察分析陕西、江苏、湖南等地出土汉兵马俑的形象,将其与相关文献记载相印证,对汉代军戎服饰形制和功能进行探讨。根据相关文献和实物考... 详细信息

本文采用文献考证与实物研究相结合的二重证据法对汉代军戎服饰的形制与功用进行考证、探究。通过观察分析陕西、江苏、湖南等地出土汉兵马俑的形象,将其与相关文献记载相印证,对汉代军戎服饰形制和功能进行探讨。根据相关文献和实物考证可发现汉代军戎服饰的品类主要有防护类的甲胄及日常穿着的戎服。军戎服饰具有一定的功能性,甲胄可以护体,护腿使将士便于活动,纹饰与徽识利于行军作战中保持部伍的整齐,并起到辨识将士身份、利于调遣的作用。军事对国家治理至关重要,研究军戎服饰对了解汉代的军事实力、作战方式以及社会审美观念等具有重要的意义。

关键词：汉代军戎服饰汉兵马俑服饰服饰形制与功用

Water-trapping and drag-reduction effects of fish Ctenopharyngodon idellus scales and their simulations

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Science China(Technological Sciences) 2017年第7期60卷 1111-1117页

作者： WU LiYan JIAO ZhiBin SONG yuqiu REN WenTao NIU ShiChao han ZhiWu College of Engineering Shenyang Agricultural University Key Laboratory of Bionic Engineering Jilin University

In the last decades, surface drag reduction has been re-emphasized because of its practical values in engineering applications,including vehicles, aircrafts, ships, and fuel pipelines. The bionic study of drag reduction has been attracting scholars' attentions. Here, it was determined that the delicate microstructures on the scales of the fish Ctenopharyngodon idellus exhibit remarkable drag-reduction effect. In addition, the underlying drag-reduction mechanism was carefully investigated. First,exceptional morphologies and structures of the scales were observed and measured using a scanning electron microscope and3-dimensional(3D) microscope. Then, based on the acquired data, optimized 3D models were created. Next, the mechanism of the water-trapping effect of these structures was analyzed through numerical simulations and theoretical calculations. It was determined that there are many microcrescent units with certain distributions on its surface. In fact, these crescents are effective in generating the "water-trapping" effect and forming a fluid-lubrication film, thus reducing the skin friction drag effectively.Contrasting to a smooth surface, the dynamics finite-element analysis indicated that the maximum drag-reduction rate of a bionic surface is 3.014% at 0.66 m/s flow rate. This study can be used as a reference for an in-depth analysis on the bionic drag reduction of boats, underwater vehicles, and so forth.

关键词：水下航行器减阻技术效果模拟草鱼扫描电子显微镜光滑表面捕鱼减阻机理

Replication of Papilio maackii Ménétriés butterfly scale structural color using a magnetron sputtering method

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Chinese Science Bulletin 2012年第34期57卷 4525-4528页

作者： WU LiYan han ZhiWu SONG yuqiu NIU ShiChao Ren LuQuan Department of Engineering Shenyang Agricultural UniversityShenyang 110161China Key Laboratory of Bionic Engineering of Ministry of Education Jilin UniversityChangchun 130025China

The natural butterfly Papilio maackii Ménétriés scales were found, through scanning and transmission electron microscopy, to comprise stacks of thin layers. Replicated scales were then fabricated on a silicon substrate using a magnetron sputtering (MS) method with ITO (In2O3(90%)+SnO2(10%)) and polymethyl methacrylate (PMMA). Finally, the optical effects of the replicated scale were examined by a spectrometer. The results showed that the replicated and natural scales have the similar characteristics in structural colors. As a result, it can be concluded that the MS method reported in this paper is a feasible method for fabricating an artificial biological structural color or other optical elements.

关键词：磁控溅射结构色复制忍冬凤蝶颜色蝴蝶聚甲基丙烯酸甲酯