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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

The Relationship Between the Gut Microbiome and Neurodegen-erative diseases

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Neuroscience Bulletin 2021年第10期37卷 1510-1522页

作者： Xueling Zhu Bo Li Pengcheng Lou Tingting Dai Yang Chen Aoxiang Zhuge Yin Yuan 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 HospitalZhejiang University School of MedicineHangzhou 310003China Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesBeijing 100730China The First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310003China

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology.Also,microbiome-based therapies have been used to improve health status and treat diseases.In addition,aging and neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease,have become topics of intense interest in biomedical research.Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease.But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear.As technology advances,new techniques for studying the microbiome will be developed and refined,and the relationship between diseases and gut microbiota will be revealed.This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases,highlighting assay techniques for the gut microbiome,and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

关键词： Gut microbiome Neurodegenerative diseases Aging 16S rRNA sequencing Multi-omics Microbiome-based therapies

What Can We Do in the Game Between Bacterial Antibiotic Resistance and Antibiotic Application?

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infectious Microbes & diseases 2022年第4期4卷 137-138页

作者： Qiong Zhang Yueyue He Xiang Li Shimiao Shao 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 Medicine Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhouZhejiangChina

It has been more than 80 years since penicillin was applied for the treatment of human bacterial infections.During this period,new antibiotics have been discovered and applied continuously.However,in order to copewith the threat of antibiotics,bacteria have also evolved by accumulating adaptive mutations or acquiring and spreading drug resistance genes.Today,the global high rate of drug resistance,1 multiple drug resistance2 and even the emergence of“super bugs”3 have posed new challenges to the treatment of bacterial infections.

关键词： Antibiotic resistance treatment

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感染微生物与疾病(英文) 2023年第3期5卷 120-126页

作者： Fei-Xiang Liu Zi-Bei Dong Min Zhao Ya-Hui Gao Xiang Li Ya-Nan Jiang Yi-Ming Li Yu-Xin Zheng Zhen Wang Yan-Chen Feng Ya-Li Liu Cerebropathy Hospital The First Affiliated Hospital of Henan University of Chinese MedicineZhengzhouChina The First Clinical Medical School Henan University of Chinese MedicineZhengzhouChina 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 MedicineHangzhouChina Research Units of Infectious disease and Microecology Chinese Academy ofMedical SciencesHangzhouChina Traditional ChineseMedicine(Zhong Jing)School Henan University of Chinese MedicineZhengzhouChina.

Coronavirus disease 2019(COVID-19)has affected the quality of sleep for various populations,causing anxiety and depression world-wide.COVID-19–related insomnia(COVIDRI)appears to be more common in certain populations,including females,urban residents and other individuals who reside in high-risk COVID-19–related areas,lack higher socioeconomic and educational levels,have a history of underlying mental illness,have no access to social support and work,or have been mandated for isolation.Among vulnerable pop-ulations,pregnant women,adolescents and children are more likely to suffer from anxiety and depression,which leads to irregular sleep-wake cycles and significantly poor sleep quality.Insomnia in COVID-19 patients is associated with decreased immune levels,ex-cessive psychological stress and severe anxiety.The COVIDRI incidence and severity among frontline healthcare workers is high,espe-cially among females and those working in isolation wards and intensive care units.The factors related to COVIDRI for college students during home study are stress from upcoming graduation,disharmonious family relationships and inadaptability to online education.For military personnel,anxiety and depression are the main causes of poor sleep quality.Based on the characteristics of different popula-tions,active Chinese and Western medications,non-drug therapy,psychological counseling and suitable sleep management are vital measures to strengthen immunity,alleviate insomnia and limit recurrence.

关键词： COVID-19 insomnia anxiety depression.

Identification of Persister Drug Combination Clinafloxacin+Cefuroxime+Gentamicin That Eradicates Persistent Pseudomonas aeruginosa Infection in a Murine Cystic Fibrosis Model

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infectious Microbes & diseases 2023年第1期5卷 21-28页

作者： Yuting Yuan Rebecca Yee Naina Gour Xinzhong Dong Jie Feng Wanliang Shi Ying Zhang Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public HealthBaltimoreMarylandUSA The Solomon H.Snyder Department of Neuroscience and the Center for Sensory Biology Johns Hopkins University School of MedicineBaltimoreMarylandUSA State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhouZhejiangChina Jinan Microecological Biomedicine Shandong Laboratory JinanShandongChina

Pseudomonas aeruginosa can cause persistent infections,such as biofilm infections,in cystic fibrosis patients,which are difficult to cure due to non-growing persister bacteria that are not effectively killed by the current treatments.While antibiotic activity against growing P.aeruginosa is well documented,their activity against non-growing stationary phase cultures is less clear.Here,we evaluated six major classes of antibiotics,including cell wall and cell membrane inhibitors,protein synthesis inhibitors,DNA synthesis inhibitors,RNA synthesis inhibitors,sulfa drugs and nitrofurantoin,for their activity against growing and non-growing P.aeruginosa.We foundthat cell wall and cell membrane inhibitors(cefuroxime and colistin),DNA synthesis inhibitors(clinafloxacin)and sulfa drugs(sulfamethoxazole)had good activity against stationary-phase bacteria,while protein synthesis inhibitors(gentamicin),RNA synthesis inhibitor(rifampin)and nitrofurantoin showed relatively poor activity.Clinafloxacin was the only drug able to completely eradicate stationary-phase bacteria within four days.The cefuroxime+gentamicin+clinafloxacin combination was able to kill all bacteria from a biofilm within two days,whereas the clinically used drug combination cefuroxime+gentamicin/colistin only partially killed the biofilmbacteria.In amurine persistent cystic fibrosis lung infectionmodel,only the cefuroxime+gentamicin+clinafloxacin drug combination eradicated all bacteria from the lungs,whereas clinafloxacin alone,cefuroxime+clinafloxacin or the currently recommended drug combination cefuroxime+gentamicin failed to do so.The complete eradication is a property of the clinafloxacin combination,as the otherwise identical levofloxacin combination did not clear the bacterial loads from the lungs.Our findings offer new therapeutic options for more effective treatment of persistent P.aeruginosa infections,with possible implications for treating other persistent infections.

关键词： Pseudomonas aeruginosa persisters stationary-phase bacteria biofilm clinafloxacin cystic fibrosis

infectious Microbes&diseases Contributing to COVID-19 Prevention and Control

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infectious Microbes & diseases 2023年第1期5卷 1-2页

作者： Qiong Zhang Yueyue He Xiang Li Shimiao Shao Stijn van der Veen 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 HospitalSchool of MedicineZhejiang UniversityHangzhouChina Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhouZhejiangChina Department of Microbiology and Department of Dermatology of Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering HangzhouChina

Since the start of the outbreak of coronavirus disease 2019(COVID-19)in January 2020,the pandemic has been raging on for 3 years,with a devastating impact on human health,resulting globally in 663,248,631 confirmed infections and 6,709,387 confirmed deaths as of January 19,2023.1 Facing this remarkably fast developing pandemic with limited knowledge on many aspects of the disease,including transmission,effective infection control,morbidity and treatment,researchers and practitioners worldwide have switched their focus to COVID-19–related research and practices.According to incomplete statistics,more than 330,000 COVID-19–related publications have been indexed in PubMed by January 19,2023,2 which carried out comprehensive and multifaceted studies on COVID-19.These research findings have played a key role in controlling the spread of COVID-19,treating severe and/or critical cases,and reducing the morbidity and mortality.

关键词： fir COV incomplete

An Evaluation Method of Human Gut Microbial Homeostasis by Testing Specific Fecal Microbiota

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Engineering 2023年第10期29卷 110-119页

作者： Zhongwen Wu Xiaxia Pan Yin Yuan Pengcheng Lou Lorina Gordejeva Shuo Ni Xiaofei Zhu Bowen Liu Lingyun Wu Lanjuan Li Bo 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 Jinan Microecological Biomedicine Shandong Laboratory Jinan 250000China Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesBeijing 100730China School of Medicine Zhejiang UniversityHangzhou 310000China Department of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200233China Department of infectious diseases Hangzhou Ninth People’s HospitalHangzhou 310003China Department of Radiation Oncology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

research on microecology has been carried out with broad perspectives in recent decades,which has enabled a better understanding of the gut microbiota and its roles in human health and disease.It is of great significance to routinely acquire the status of the human gut microbiota;however,there is no method to evaluate the gut microbiome through small amounts of fecal microbes.In this study,we found ten predominant groups of gut bacteria that characterized the whole microbiome in the human gut from a large-sample Chinese cohort,constructed a real-time quantitative polymerase chain reaction(qPCR)method and developed a set of analytical approaches to detect these ten groups of predominant gut bacterial species with great maneuverability,efficiency,and quantitative features.Reference ranges for the ten predominant gut bacterial groups were established,and we found that the concentration and pairwise ratios of the ten predominant gut bacterial groups varied with age,indicating gut microbial dysbiosis.By comparing the detection results of liver cirrhosis(LC)patients with those of healthy control subjects,differences were then analyzed,and a classification model for the two groups was built by machine learning.Among the six established classification models,the model established by using the random forest algorithm achieved the highest area under the curve(AUC)value and sensitivity for predicting LC.This research enables easy,rapid,stable,and reliable testing and evaluation of the balance of the gut microbiota in the human body,which may contribute to clinical work.

关键词： Gut microbiota Machine learning Microbial dysbiosis Quantitative polymerase chain reaction Chinese cohort

Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules

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Bioactive Materials 2022年第9期7卷 305-315页

作者： Bo Li Xin Li Xiaodong Chu Pengcheng Lou Yin Yuan Aoxiang Zhuge Xueling Zhu Yangfan Shen Jinghua Pan Liyuan Zhang Lanjuan Li Zhongwen Wu 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 UniversityHangzhou310003China Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesBeijing100730China Department of Pharmacology The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310003China Department of General Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou510632China School of Engineering and Applied Sciences Harvard University9 Oxford StCambridgeMAUSA02138 School of Petroleum Engineering State Key Laboratory of Heavy Oil ProcessingChina University of Petroleum(East China)Qingdao266580China

In-situ oral delivery of therapeutic antibodies,like monoclonal antibody,for chronic inflammation treatment is the most convenient approach compared with other administration routes.Moreover,the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation.However,the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions.Moreover,these antibodies have short serum half-lives,thus,require to be frequently administered with high doses to be effective,leading to low patient tolerance.Here,we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier.By encapsulating antibodies in these microcapsules,antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route,achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model.Moreover,the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery,implying the restoration of micro-ecology of the intestine.These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.

关键词： Antibody oral delivery Hydrogel thin-shell microcapsules Microfluidic Gut microbiota Colonic inflammation Micro-ecology restoration

Exploring the multicomponent synergy mechanism of Zuogui Wan(左归丸) on postmenopausal osteoporosis by a systems pharmacology strategy

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Journal of Traditional Chinese Medicine 2024年第3期44卷 489-495页

作者： FENG Yanchen LIU Yali DANG Xue LIN Zixuan ZHANG Yunke CHE Zhiying LI Xiang PAN Xiaolong LIU Feixiang ZHENG Pan Traditional Chinese Medicine (Zhong Jing) School Henan University of Chinese Medicine Hospital of Encephalopathy the First Affiliated Hospital of Henan University of Chinese Medicine 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 MedicineResearch Units of Infectious Disease and MicroecologyChinese Academy of Medical Sciences

OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan(左归丸, ZGW) in treating postmenopausal osteoporosis(PMOP). METHODS: The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology(TCMSP). In addition, the target gene sets of PMOP were derived from the Gene Cards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes(STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient(MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated(Sham) group and the four ovariectomized(OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle(OVX, 1 m L water/100 g weight), 17β-estradiol(E2, 50 μg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3(ZGW-L) and high dose of 4.6(ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immunosorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. RESULTS: A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8(CXCL8), C-C chemokine receptor type 2(CCR2), alpha-2a active receptor(ADRA2A), melatonin receptor type 1B(MTNR1B), and amyloid-beta A4 protein(APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of β-C-terminal telopeptide of type I collagen(β-CTX) and increased serum levels of bone-specific al

关键词： network pharmacology osteoporosis, postmenopausal Zuogui Wan