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Metagenomic sequencing reveals high reproducibility of human donor microbiota transplanted into germ-free mice via lower gut route 认领 引用
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作者 Yapeng YANG Xiang TAN +12 位作者 Zeyue ZHANG Lifeng LIANG Zhifeng WU Jinhui HE Yuqing WANG Miaomiao DONG Jixia ZHENG Hang ZHANG Shuaifei FENG Wei CHENG Bota CUI Hong WEI Qinjin LI 《Journal of Zhejiang University-SCIENCE B》 SCIE CAS CSCD 2026年第4期375-389,共15页
Human flora-associated(HFA)mice are often used to simulate the structure of human intestinal microbiota and to study the causal relationships between diseases and gut microbiota.However,several factors affect the colo... Human flora-associated(HFA)mice are often used to simulate the structure of human intestinal microbiota and to study the causal relationships between diseases and gut microbiota.However,several factors affect the colonization efficiency of human microbiota in germ-free(GF)mice,and the differential effects of gavage and lower gut transplantation on colonization are still unclear.In this study,we explored the reproducibility of the recipient-to-donor gut microbiota community structure and function under different transplantation routes and the differences in microbial colonization between recipients via gavage transplantation(GT_mice group)and lower gut transplantation(LGT_mice group).High-throughput sequencing of the metagenome was performed on the feces of each subject,and the composition of microbiome of each group was analyzed.As expected,the introduction of human fecal microbiota into GF mice via lower gut transplantation had a high transfer efficiency,which was evident from the similar species community structure to that of the donor(Adonis R2=0.713960 for LGT_mice group–donor group;Adonis R2=0.774095 for GT_mice group–donor group)and a higher bacterial colonization rate.The findings provide unique insights into improving the accuracy of constructing humanized microbiota transplantation models,aiding our understanding of the relationships between the human gut microbiota and disease. 展开更多
关键词 Fecal microbiota transplantation Germ-free mice Lower gut Gavage Metagenome
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Early diabetes-like phenotypes in germ-free mice induced by gut microbiota from patients with type 2 diabetes 认领 引用
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作者 Jianghao Feng Xing Liu +4 位作者 Hua Zhu Yun Yang Wei Liu Xiaoliang Jiang Zhiwei Yang 《Animal Models and Experimental Medicine》 CAS CSCD 2026年第6期1202-1216,共15页
Background:The contribution of gut microbiota to the early stage of type 2 diabetes(T2D)remains incompletely understood.This study established a germ-free mouse model colonized with gut microbiota from donors with T2D... Background:The contribution of gut microbiota to the early stage of type 2 diabetes(T2D)remains incompletely understood.This study established a germ-free mouse model colonized with gut microbiota from donors with T2D to determine whether diabetes-associated microbiota could induce early diabetes-like phenotypes.Methods:Human fecal samples were collected from 18 healthy donors and 14 donors with T2D for microbiota profiling.Based on these features,samples from 12 healthy donors and 3 donors with T2D were selected,pooled within each group,and transplanted into germ-free mice,generating a healthy microbiota recipient group(HM,n=14)and a diabetes-associated microbiota recipient group(DM,n=13).Glucose homeostasis was assessed over 10 weeks using fasting blood glucose and intraperitoneal glucose tolerance tests.Gut microbial succession was analyzed by 16S rRNA sequencing.Fecal and plasma metabolomics were performed to identify metabolic and their associations with microbial changes.Results:DM mice developed an early diabetes-like phenotype characterized by progressive impairment of glucose tolerance,reduced insulin levels,and mild renal alterations,without sustained overt fasting hyperglycemia.Microbial divergence emerged before stable metabolic dysfunction and was accompanied by persistent dysbiosis in DM mice.Integrated metabolomic analysis identified coordinated alterations in fecal and plasma metabolites,with cholic acid and L-Dopa decreased in both compartments.L-Dopa showed consistent associations with altered genera,particularly Ruminococcus and Sellimonas.Conclusions:Transplanting diabetes-associated human gut microbiota effectively induced early glucose dysregulation in germ-free recipient mice.This model provides a framework for studying microbiota-associated events during early T2D-related metabolic deterioration. 展开更多
关键词 germ-free mice metabolomics microbiomics microbiota transplantation type 2 diabetes
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Single-cell RNA-seq provides insight into the underdeveloped immune system of germ-free mice 认领 引用
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作者 Yi-Fei Sheng Wei Cheng +15 位作者 Yin Zhang Qi-Jun Liao Juan Shen Rui-Zhen Zhao Tai-Liang Chai Chao Wu Wei-Ning Hu Xiang Huang Bo Wei Shan-Shan Pan Yang-Rui Zhang Rou-Xi Chen Jun-Pu Mei Hong Wei Li-Juan Han Xiao-Dong Fang 《Zoological Research》 SCIE CAS CSCD 2025年第4期812-824,共13页
Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking micr... Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking microbiota absence to systemic immune deficits remain incompletely defined.Here,droplet-based single-cell RNA sequencing of bone marrow and peripheral blood from both germ-free and specific pathogen-free mice was performed,identifying 25 transcriptionally distinct cell types.Neutrophil apoptosis was elevated in germ-free mice,potentially due to the absence of niacin dehydrogenase,a metabolite primarily produced by Pseudomonas.In addition,germ-free mice exhibited increased excretion of 5’-methylthioadenosine,enhanced ERK activation driven by reactive oxygen species,and disruption of bone marrow stromal antigen 2 signaling.Monocytes and CD8+T cells from germ-free mice showed diminished responses to interferon-β and interferon-γ,consistent with heightened viral susceptibility.These findings establish a microbiota-dependent regulatory pathway linking immunodeficiency to microbial absence in germ-free mice,confirmed through complementary validation techniques. 展开更多
关键词 Germ-free mice Microbiota Single-cell RNA sequencing Underdeveloped immune system
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Investigation of the metabolites of five major constituents from Berberis amurensis in normal and pseudo germ-free rats 认领 引用 被引量：4
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作者 LIAO Cui-Ping LIU Xing-Chao +7 位作者 DONG Shi-Qi AN Ming ZHAO Lu ZHANG Ai-Jie LIU Jian-Feng HOU Wen-Bin FAN Hui-Rong LIU Chang-Xiao 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2021年第10期758-771,共14页
Berberis amurensis(Berberidaceae)is a traditional Chinese medicine,which is often used to treat hypertension,inflammation,dysentery and enteritis.It contains alkaloids,mainly including berberine,berbamine,magnoflorine... Berberis amurensis(Berberidaceae)is a traditional Chinese medicine,which is often used to treat hypertension,inflammation,dysentery and enteritis.It contains alkaloids,mainly including berberine,berbamine,magnoflorine,jatrorrhizine and palmatine.Berberis amurensis extracts(BAEs)is often orally taken.Oral herbs might be metabolized by intestinal bacteria in the small intestine.However,the interaction between the herb and the gut microbiota is still unknown.In the current study,UPLC/Q-TOFMS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats.As a result,a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation,dehydrogenation,methylation,hydroxylation,sulfation and glucuronidation.Only 29 metabolites existed in pseudo germ-free rats.Dehydrogenated metabolites(M29,M30,M34 and M36),methylated metabolites(M33,M41 and M46)and other metabolites were not detected in pseudo germ-free rats.The result implied that the intestinal bacteria have an influence on the metabolism of BAEs.Furthermore,this investigation might contribute to the understanding of the metabolism of BAEs,and further promote its clinical application. 展开更多
关键词 Berberis amurensis Berberidaceae Pseudo germ-free rat Intestinal flora UPLC/Q-TOF-MS/MS
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Carrageenan oligosaccharides and associated carrageenan-degrading bacteria induce intestinal inflammation in germ-free mice 认领 引用 被引量：2
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作者 Yeshi Yin Miaomiao Li +9 位作者 Weizhong Gu Benhua Zeng Wei Liu Liying Zhu Xionge Pi Donald A.Primerano Hongwei D.Yu Hong Wei Guangli Yu Xin Wang 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2021年第9期815-824,共10页
Carrageenans(CGNs)are widely used in foods and pharmaceuticals although their safety remains controversial.To investigate the effects of CGNs and CGN-degrading bacteria in the human colon,we screened for CGN degradati... Carrageenans(CGNs)are widely used in foods and pharmaceuticals although their safety remains controversial.To investigate the effects of CGNs and CGN-degrading bacteria in the human colon,we screened for CGN degradation by human fecal microbiota,and for inflammatory response to CGNs and/or CGN-degrading bacteria in germ free mice.Thin-layer chromatography indicated that high molecular weight(MW)CGNs(!100 kDa)remained undegraded in the presence of human fecal microbiota,whereas low MW CGNs,i.e.,k-carrageenan oligosaccharides(KCO,~4.5 kDa)were degraded when exposed to seven of eight human fecal samples,although sulfate groups were not removed during degradation.Bacteroides xylanisolvens and Escherichia coli isolates from fecal samples apparently degraded KCO synergistically,with B.xylanisolvens serving as the primary degrader.Combined treatment of KCO with KCO-degrading bacteria led to greater pro-inflammatory effects in the colon and rectum of germ-free mice than either KCO or bacteria alone.Similarly,p-p38-,CD3-,and CD79a-positive immune cells were more abundant in combined treatment group mice than in either single treatment group.Our study shows that KCO-degrading bacteria and the low MW products of KCO can promote proinflammatory effects in mice,and represent two key markers for evaluating CGN safety in foods or medicines. 展开更多
关键词 Carrageenans Carrageenan oligosaccharides Oligosaccharide degrading bacteria Intestinal inflammatory Germ-free mouse
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Impaired inactivation of digestive proteases:The possible key factor for the high susceptibility of germ-free and antibiotic-treated animals to gut epithelial injury 认领 引用
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作者 Xiaofa Qin 《World Journal of Gastrointestinal Pathophysiology》 2017年第1期1-2,共2页
Recent study shows that germ-free and antibiotic-treated animals are highly susceptible to gut epithelial injury. This paper addresses that impaired inactivation of digestive proteases may be the key factor for the in... Recent study shows that germ-free and antibiotic-treated animals are highly susceptible to gut epithelial injury. This paper addresses that impaired inactivation of digestive proteases may be the key factor for the increased susceptibility. 展开更多
关键词 Digestive proteases Germ-free Antibiotics Gut microbiota Gut epithelial injury
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The metabolism of constituents of Huangqin- Tang decoction,a traditional Chinese medicinal preparation,in conventional, germ-free and gnotobiote mice 认领 引用
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《中国实验方剂学杂志》 CAS 2002年第S1期
IntroductionIntestinalbacteriaplayanessentialroleinthemetabolismofmanyglycosidesinvariousmedicinalherbstotheiraglycones[1] .Someglycosidesofherbsareconsideredtobemaincompo nentsinmanifestationoftheirmedicineeffects[2 ... IntroductionIntestinalbacteriaplayanessentialroleinthemetabolismofmanyglycosidesinvariousmedicinalherbstotheiraglycones[1] .Someglycosidesofherbsareconsideredtobemaincompo nentsinmanifestationoftheirmedicineeffects[2 ] .Inpreviouspaper ,usinganHPLCmethodes tablishedinourlaboratory ,1 5chemicalcomponentsincludingtheoriginalcompoundsinthetra ditionalChinesemedicinalpreparationHuangqin TangandtheirmetabolitesbyHIBweresi multaneouslyidentifiedanddetermined .TheresultsshowedthattheglycosidesofHuangqin TangBG ,WG... 展开更多
关键词 Huangqin-Tang decoction metabolism intestinal bacteria germ-free mice gnotobiote mice
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Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization 认领 引用 被引量：17
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作者 Hana Kozakova Martin Schwarzer +11 位作者 Ludmila Tuckova Dagmar Srutkova Elzbieta Czarnowska Ilona Rosiak Tomas Hudcovic Irma Schabussova Petra Hermanova Zuzana Zakostelska Tamara Aleksandrzak-Piekarczyk Anna Koryszewska-Baginska Helena Tlaskalova-Hogenova Bozena Cukrowska 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2016年第2期251-262,共12页
Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobaci... Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v I using a gnotobiotic mouse model. We showed that Lactobacillus （L.） rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 （TLR2） and nucleotide-binding oligomerization domain-containing protein 2 （NOD2） receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free （GF） mice with a mixture of all three strains （Lmix） improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v I allergen showed significantly lower levels of allergen-specific IgE, IgG 1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor （TGF）-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans, 展开更多
关键词 allergic sensitization germ-free intestinal barrier Lactobacillus probiotics
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Gut microbiota absence and transplantation affect growth and intestinal functions:An investigation in a germ-free pig model 认领 引用 被引量：13
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作者 Hua Zhou Jing Sun +11 位作者 Bing Yu Zuohua Liu Hong Chen Jun He Xiangbing Mao Ping Zheng Jie Yu Junqiu Luo Yuheng Luo Hui Yan Liangpeng Ge Daiwen Chen 《Animal Nutrition》 SCIE CAS CSCD 2021年第2期295-304,共10页
This study was conducted to investigate host-microbiota interactions and explore the effects of maternal gut microbiota transplantation on the growth and intestinal functions of newborns in a germ-free(GF)pig model.Tw... This study was conducted to investigate host-microbiota interactions and explore the effects of maternal gut microbiota transplantation on the growth and intestinal functions of newborns in a germ-free(GF)pig model.Twelve hysterectomy-derived GF Bama piglets were reared in 6 sterile isolators.Among them,6 were considered as the GF group,and the other 6 were orally inoculated with healthy sow fecal suspension as fecal microbiota transplanted(FMT)group.Another 6 piglets from natural birth were regarded as the conventional(CV)group.The GF and FMT groups were hand-fed with Co60-y-irradiated sterile milk powder,while the CV group was reared by lactating Bama sows.All groups were fed for 21 days.Then,all piglets and then were switched to sterile feed for another 21 days.Results showed that the growth performance,nutrient digestibility,and concentrations of short-chain fatty acids in the GF group decreased(P<0.05).Meanwhile,the serum urea nitrogen concentration and digesta pH values in the GF group increased compared with those in the FMT and CV groups(P<0.05).Compared with the CV group,the GF group demonstrated upregulation in the mRNA expression levels of intestinal barrier function-related genes in the small intestine(P<0.05).In addition,the mRNA abundances of intestinal development and absorption-related genes in the small intestine and colon were higher in the GF group than in the CV and FMT groups(P<0.05).The FMT group exhibited greater growth performance,lipase activity,and nutrient digestibility(P<0.05),higher mRNA expression levels of intestinal development and barrier-related genes in the small intestine(P<0.05),and lower mRNA abundances of pro-inflammatory factor in the colon and jejunum(P<0.05)than the CV group.In conclusion,the absence of gut microbes impaired the growth and nutrient digestibility,and healthy sow gut microbiota transplantation increased the growth and nutrient digestibility and improved the intestinal development and barrier function of newborn piglets,indicating the importance of intestinal microbes for intestinal development and functions. 展开更多
关键词 Germ-free Host microbiota interaction Maternal gut microbiota transplantation Growth performance Intestinal function Pig model
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Consistent Alterations of Human Fecal Microbes After Transplantation into Germ-free Mice 认领 引用 被引量：8
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作者 Yanze Li Wenming Cao +2 位作者 Na L Gao Xing-Ming Zhao Wei-Hua Chen 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2022年第2期382-393,共12页
Fecal microbiota transplantation(FMT)of human fecal samples into germ-free(GF)mice is useful for establishing causal relationships between the gut microbiota and human phenotypes.However,due to the intrinsic differenc... Fecal microbiota transplantation(FMT)of human fecal samples into germ-free(GF)mice is useful for establishing causal relationships between the gut microbiota and human phenotypes.However,due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms,it may not be possible to replicate human phenotypes in mice through FMT;similarly,treatments that are effective in mouse models may not be effective in humans.In this study,we aimed to identify human gut microbes that undergo significant and consistent changes(i.e.,in relative abundances)after transplantation into GF mice in multiple experimental settings.We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human–mouse pairs.Strikingly,on average,we found that only 47%of the human gut microbes could be re-established in mice at the species level,among which more than 1/3 underwent significant changes(referred to as“variable taxa”).Most of the human gut microbes that underwent significant changes were consistent across multiple human–mouse pairs and experimental settings.Consequently,about 1/3 of human samples changed their enterotypes,i.e.,significant changes in their leading species after FMT.Mice fed with a controlled diet showed a lower enterotype change rate(23.5%)than those fed with a noncontrolled diet(49.0%),suggesting a possible solution for rescue.Most of the variable taxa have been reported to be implicated in human diseases,with some recognized as the causative species.Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes,provide useful information for researchers using mice in gut microbiota studies,and call for additional validations after FMT.An online database named FMT-DB is publicly available at http://gffzz31fc3efd07a444b1hpuo5v9v9wu0b6kvn.ffgz.tsg.suse.edu.cn/#/. 展开更多
关键词 Germ-free mice Fecal microbiota transplantation Gut microbe Enterotype 16S rDNA
Characterizing the influence of gut microbiota on host tryptophan metabolism with germ-free pigs 认领 引用 被引量：3
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作者 Bingnan Liu Dongming Yu +7 位作者 Jing Sun Xiaoyan Wu Zhongquan Xin Baichuan Deng Lijuan Fan Jian Fu Liangpeng Ge Wenkai Ren 《Animal Nutrition》 SCIE CAS CSCD 2022年第4期190-200,共11页
Intestinal microbes are closely associated with host health,depending on metabolic crosstalk between the microbiota and host.Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal ... Intestinal microbes are closely associated with host health,depending on metabolic crosstalk between the microbiota and host.Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal microbiota and host;however,our understanding about the influence of intestinal microbiota on host tryptophan metabolism is limited.Thus,we established germ-free(GF)pig models to systemically explore the influence of intestinal microbiota on tryptophan metabolism.Five GF pigs were kept in GF conditions throughout the experiment(GF group).Six GF pigs were transplanted with fecal microbiota from donor sows to act as control pigs.Compared with control pigs,the GF pigs had remarkable alterations in tryptophan metabolism.The differential metabolites(P<0.05)were mainly found in the liver,circulation system and large intestine.Notably,the alteration of metabolites in tryptophan metabolism varied among organs,especially for the serotonin pathway.In GF pigs,tryptophan and kynurenine in the large intestine and 5-hydroxytryptophan in most organs were increased(P<0.05),while metabolites in the indole pathway in most organs were decreased(P<0.05).Collectively,our study reveals changes in tryptophan metabolism in GF pigs,highlighting the critical role of gut microbes in shaping host tryptophan metabolism. 展开更多
关键词 Germ-free pig Gut microbiota Tryptophan Indole Kynurenine
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Evaluation of the Mechanisms Underlying Amino Acid and Microbiota Interactions in Intestinal Infections Using Germ-Free Animals 认领 引用 被引量：3
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作者 Yapeng Yang Peng Bin +5 位作者 Shiyu Tao Guoqiang Zhu Zhifeng Wu Wei Cheng Wenkai Ren Hong Wei 《Infectious Microbes & Diseases》 CSCD 2021年第2期79-86,共8页
Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorgani... Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorganisms colonize the intestinal tract of healthy people,which together with the intestinal epithelium constitute the biological barrier of the intestinal tract to resist infectious diseases.As an“invisible organ,”the intestinal flora is closely related to human nutrition metabolism and intestinal infections.A variety of intestinal flora participates in the nutritional metabolism of amino acids,and the small molecular substances produced by the amino acid metabolism through the intestinal flora can enhance intestinal immunity and resist bacterial infections.In turn,amino acids can also regulate the composition of the intestinal flora,maintain the steady-state of the intestinal flora,protect the intestinal barrier,and inhibit colonization by pathogenic bacteria.As a model animal with a clear microbial background,germ-free(GF)animals can clarify the mechanisms of interactions between intestinal microbes and amino acid metabolism in intestinal infections by combining genetic engineering technology and multi-omics studies.This article reviews related researches on the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections and discusses the advantages of GF animal models for studying the underlying mechanisms.The GF animal model is helpful to further study the intervention effects of amino acid metabolism of targeted intestinal flora on intestinal infections. 展开更多
关键词 germ-free animal intestinal barrier intestinal flora intestinal immunity intestinal infection metabolism of amino acids
Establishment of an efficient germ-free animal system to support functional microbiome research 认领 引用 被引量：13
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作者 Jian Li Hong Wei 《Science China(Life Sciences)》 SCIE CAS CSCD 2019年第10期1400-1403,共4页
Germ-free animals are indispensable models for human and animal functional microbiome research Germ-free animals are animals that typically have no microorganisms living in or on them. These animals have become irrepl... Germ-free animals are indispensable models for human and animal functional microbiome research Germ-free animals are animals that typically have no microorganisms living in or on them. These animals have become irreplaceable research tools for studying the relationships among single bacteria strains, multiple bacteria strains and hosts. 展开更多
关键词 bacteria irreplaceable Germ-free
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Dietary nitrate drives gastritis by modulating gastric microbiota and metabolites 认领 引用
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作者 Lanping Jiang Tianhui Li +10 位作者 Jiayu Wu Harry Cheuk Hay Lau Chi Chun Wong Xingyu Zhou Alvin Ho Kwan Cheung Qinyao Wei Jing Ren Xiang Zhang Qing Li Yongzhan Nie Jun Yu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第5期717-736,共20页
Objective:Dietary nitrate has been increasingly recognized as a potential carcinogen associated with gastritis.In this study the mechanistic role of a high-nitrate diet(NaD)in driving gastritis was elucidated with a f... Objective:Dietary nitrate has been increasingly recognized as a potential carcinogen associated with gastritis.In this study the mechanistic role of a high-nitrate diet(NaD)in driving gastritis was elucidated with a focus on modulation of the gastric microbiota composition and metabolomic profiles.Methods:Animals were randomly assigned to two dietary intervention groups using a C57BL/6 mouse model:a NaD containing 7.5%nitrate;or a standard normal diet(ND).Gastric microbiota composition was characterized based on full-length 16S rRNA sequencing and gastric metabolite profiles were analyzed using high-performance liquid chromatography-mass spectrometry(HPLC/MS).Finally,the roles of the microbiome and metabolites in gastritis development were validated using the human gastric epithelial cell line(GES-1),as well as conventional and germ-free mouse models.Results:NaD induced gastritis in conventional mice compared to ND-fed mice.In addition,NaD incited the infiltration of macrophages and neutrophils with elevated levels of inflammatory cytokine genes(IL-17a,Ccl20,Cxcl5,IL-6,and Ccl2).A significant shift in the composition of the gastric microbiota occurred with an increase in pathogenic bacteria(Enterococcus gallinarum,Prevotella timonensis,and Mycobacterium gordona)and a decrease in probiotics(Roseburia hominis,Clostriduim scindens,and Faecalibacterium prausnitzii).Furthermore,NaD induced alterations in the metabolic profile,marked by an elevated level of 5-hydroxyindoleacetate(5-HIAA),a key downstream metabolite of the tryptophan metabolic pathway.Notably,5-HIAA also upregulated the levels of inflammatory cytokines in the human gastric epithelial GES-1 cell line.In addition,both E.gallinarum colonization and 5-HIAA exposure significantly increased inflammatory responses in conventional and germ-free mouse models.Conclusions:NaD drives gastritis in mice by inducing gastric microbial dysbiosis and metabolomic dysregulation with elevated 5-HIAA. 展开更多
关键词 Nitrate diet gastritis Enterococcus gallinarum 5-HIAA germ-free mouse
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无菌动物模型在结直肠癌及中医药研究中的应用进展 认领 引用 被引量：1
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作者 钱紫星 李家旋 +3 位作者 饶显俊 黄国栋 刘然 魏玮 《中国中药杂志》 CAS CSCD 北大核心 2026年第1期32-39,共8页
结直肠癌(CRC)是全球高发的恶性肿瘤,其发生发展与肠道菌群紊乱密切相关。无菌(GF)动物模型通过提供无固有微生物的独特环境,成为精准解析肠道菌群在CRC发生、发展中因果作用及药物疗效机制的工具。该综述旨在系统阐述GF动物模型在CRC... 结直肠癌(CRC)是全球高发的恶性肿瘤,其发生发展与肠道菌群紊乱密切相关。无菌(GF)动物模型通过提供无固有微生物的独特环境,成为精准解析肠道菌群在CRC发生、发展中因果作用及药物疗效机制的工具。该综述旨在系统阐述GF动物模型在CRC研究中的应用进展,重点总结利用该模型揭示的特定微生物促进CRC发生发展的关键机制。同时聚焦中医药在该领域的研究动态,系统阐述GF动物模型在中医药抗CRC研究中的应用。通过对CRC无菌动物模型的深入解析,未来可能开发出基于中医药、微生物组的精准诊断和治疗策略,为CRC的防治提供新的方向和思路。 展开更多
关键词 无菌动物 肠道菌群 中医药 结直肠癌
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无菌中国地鼠模型建立 认领 引用
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作者 郭亚茜 刘凯慧 +2 位作者 杜晓鹏 王昭华 朱华 《中国实验动物学报》 CAS CSCD 北大核心 2026年第2期206-212,共7页
目的 使用剖宫产净化(cesarean section purification)方法建立无菌中国地鼠模型。方法 供胎母鼠选择SPF级中国地鼠,雌雄按1∶1进行交配,见栓后与雄鼠分开饲养。代乳母鼠的合笼时间早于供胎母鼠1~2 d。怀孕的中国地鼠临产时在超净工作... 目的 使用剖宫产净化(cesarean section purification)方法建立无菌中国地鼠模型。方法 供胎母鼠选择SPF级中国地鼠,雌雄按1∶1进行交配,见栓后与雄鼠分开饲养。代乳母鼠的合笼时间早于供胎母鼠1~2 d。怀孕的中国地鼠临产时在超净工作台内进行子宫摘除术,传入净化用隔离包内,剥离子宫获得待净化乳鼠,使用无菌级ICR小鼠进行代乳,成功离乳后转入饲养用隔离包内。每月对饲养用隔离包进行无菌状态检测。结果 共实施2次剖宫产手术,第1次代乳失败;第2次代乳成功,获得仔鼠9只,离乳存活率56%,依照GB/T 14926.41-2001进行无菌中国地鼠状态检测均为合格。结论 通过剖宫产净化技术,使用无菌级ICR小鼠进行代乳,达到微生物净化目的,获得无菌化中国地鼠模型。 展开更多
关键词 中国地鼠 无菌动物 剖宫产净化 隔离器
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联合抗生素对伪无菌模型大鼠的肠道菌群及其代谢的影响 认领 引用
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作者 贺莉 颜家朝 喻京生 《中国现代医学杂志》 CAS 2026年第3期32-43,共12页
目的比较联合抗生素经灌胃与自由饮水两种给药复制大鼠伪无菌模型的效果,为优化伪无菌模型复制方法提供参考。方法将SD大鼠随机分为正常组、抗生素灌胃组和抗生素饮水组,每组5只。抗生素灌胃组采用含200 mg/mL氨苄西林、200 mg/mL甲硝唑... 目的比较联合抗生素经灌胃与自由饮水两种给药复制大鼠伪无菌模型的效果,为优化伪无菌模型复制方法提供参考。方法将SD大鼠随机分为正常组、抗生素灌胃组和抗生素饮水组,每组5只。抗生素灌胃组采用含200 mg/mL氨苄西林、200 mg/mL甲硝唑、200 mg/mL新霉素和100 mg/mL万古霉素的混悬液,按1 mL/kg体积每日灌胃;抗生素饮水组在灭菌饮用水中加入0.5 g/L氨苄西林、0.5 g/L甲硝唑、0.5 g/L新霉素和0.25 g/L万古霉素,大鼠自由饮水,干预14 d。干预后第5、10、14天,无菌取大鼠粪便进行菌群培养;14 d后取大鼠粪便进行16S核糖体rDNA(16S rDNA)测序;分离肝脏、脾脏、肾脏、胸腺称重,取各组大鼠结肠组织进行苏木精-伊红(HE)染色及免疫组织化学染色。结果与正常组比较,在有氧和厌氧培养条件下,第5天起抗生素灌胃组和抗生素饮水组粪便菌落显著减少,伪无菌大鼠模型复制成功并稳定维持到第14天。与正常组比较,抗生素饮水组第2~6天体重均下降(P0.05);抗生素灌胃组第6天体重高于正常组(P0.05)。各组大鼠结肠免疫组织化学结果显示,与正常组比较,抗生素灌胃组与抗生素饮水组中紧密连接蛋白闭锁小带蛋白-1(ZO-1)、闭合蛋白(Occludin)在肠上皮和腺上皮细胞细胞质及细胞膜呈阳性表达,棕黄色染色较多。基于16S rDNA测序的α多样性分析显示:与正常组比较,抗生素灌胃组和抗生素饮水组的ACE、Sobs及Shannon指数均降低(P0.05);正常组厚壁菌门、拟杆菌门及放线菌门丰度高于抗生素灌胃组和抗生素饮水组(均P<0.05)。抗生素饮水组摩根菌属丰度高于抗生素灌胃组和正常组(均P<0.05);抗生素灌胃组埃希-志贺菌属丰度高于抗生素饮水组和正常组(P<0.05);正常组乳酸杆菌属、拟杆菌属及norank_f__Muribaculaceae属丰度高于抗生素灌胃组和抗生素饮水组(均P<0.05)。基于KEGG的菌群功能预测分析结果显示:在碳水化合物代谢、氨基酸代谢、能量代谢、萜类化合物和聚酮类化合物代谢、辅助因子和维生素代谢等多个途径上,3组预测丰度的总体比较,差异均有统计学意义(P<0.05)。结论联合抗生素经灌胃和自由饮水给药均可在14 d内有效复制SD大鼠伪无菌模型,但抗生素灌胃组与抗生素饮水组均出现条件致病菌异常繁殖现象,这提示抗生素干预可能通过筛选压力改变菌群结构,使原本处于低丰度的潜在致病菌获得生长优势。这为研究者根据实验目标菌群选择适宜的抗生素给药策略复制伪无菌模型提供了参考。 展开更多
关键词 16s rDNA测序 伪无菌大鼠 肠道屏障 闭锁小带蛋白-1 闭合蛋白 抗生素联合使用
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肠道微生物对无菌鸡生长性能、肠道发育与机体代谢影响的研究进展 认领 引用
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作者 暴雨婷 侯飞雪 +6 位作者 张翠珍 朱懿可 刘文静 刘瑾 冯佳露 黎观红 周华 《中国家禽》 CAS 北大核心 2026年第9期134-139,共6页
肠道微生物在宿主生长发育和代谢调控中发挥关键作用。无菌鸡作为完全排除背景微生物干扰的理想模型,具备繁殖周期短和成本可控等优势。在此基础上构建携带特定微生物的悉生动物模型,可用于探究特定微生物致病机制和宿主-微生物的互作... 肠道微生物在宿主生长发育和代谢调控中发挥关键作用。无菌鸡作为完全排除背景微生物干扰的理想模型,具备繁殖周期短和成本可控等优势。在此基础上构建携带特定微生物的悉生动物模型,可用于探究特定微生物致病机制和宿主-微生物的互作研究。无菌鸡因缺乏肠道微生物,在生长性能、肠道发育及机体代谢等方面呈现独特表型。肠道微生物不仅通过辅助营养摄取和调节氮代谢促进鸡的生长发育和蛋白质沉积,还通过调控宿主基因表达及介导胆汁酸代谢等途径影响宿主的脂质沉积。文章综述了肠道微生物对无菌鸡生长性能、肠道发育及机体代谢影响的研究进展,以期为家禽营养调控和肠道健康研究提供理论依据。 展开更多
关键词 无菌鸡 常规鸡 肠道微生物 动物模型
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基于铜死亡相关长链非编码RNA的睾丸生殖细胞肿瘤预后模型构建与验证 认领 引用
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作者 盛正成 尤嘉玮 +4 位作者 陈宇豪 周昱霖 沈天一 周文泉 商学军 《中华男科学杂志》 CAS CSCD 2026年第7期591-597,共7页
目的筛选铜死亡相关长链非编码RNA(lncRNA)并构建预后模型,为睾丸生殖细胞肿瘤(TGCT)患者提供精准预后评估工具。方法整合TCGA转录组数据及临床信息,通过共表达分析筛选与铜死亡基因显著相关的lncRNA(|R|>0.5,P<0.05)。在训练集... 目的筛选铜死亡相关长链非编码RNA(lncRNA)并构建预后模型,为睾丸生殖细胞肿瘤(TGCT)患者提供精准预后评估工具。方法整合TCGA转录组数据及临床信息,通过共表达分析筛选与铜死亡基因显著相关的lncRNA(|R|>0.5,P<0.05)。在训练集中采用LASSO回归构建风险评分模型,并在测试集中验证。通过时间依赖性受试者工作特征(ROC)曲线、Kaplan-Meier生存分析、单因素及多因素Cox回归评估模型效能。结果共筛选出11个与铜死亡基因显著相关的lncRNA,LASSO回归进一步确定3个关键lncRNA(AC002456.2、AC004069.2、AC005498.3)构建风险评分模型。在测试集中,模型预测1、2、3年无复发生存期(RFS)的曲线下面积(AUC)分别为0.691、0.599和0.749。高风险组患者RFS显著短于低风险组(P<0.05),训练集和测试集的中位RFS时间分别为328 d vs 810 d和430 d vs 816 d。多因素Cox回归显示,风险评分分组(P=0.01)和S分期是RFS的独立预后因素。风险评分与T分期、S分期显著相关(P<0.05)。结论本研究成功构建了一个基于3个铜死亡相关lncRNA的预后模型。该模型能有效预测TGCT患者的RFS,为个体化预后评估提供了新工具,并为探索铜死亡相关lncRNA的调控机制提供参考。 展开更多
关键词 睾丸生殖细胞肿瘤 铜死亡 长链非编码RNA 预后模型 无复发生存 TCGA数据库
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Effects of capsaicin on intestinal health under antibiotic exposure 认领 引用
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作者 Qingying Fang Leilei Yu +2 位作者 Fengwei Tian Wei Chen Qixiao Zhai 《Food Science and Human Wellness》 SCIE CAS CSCD 2025年第7期2530-2541,共12页
Antibiotic exposure has adverse effects on intestinal immunity,metabolism,and gut microbiota(GM)composition,particularly by disturbing GM composition without short-term recovery.Capsaicin,a dietary irritant,is general... Antibiotic exposure has adverse effects on intestinal immunity,metabolism,and gut microbiota(GM)composition,particularly by disturbing GM composition without short-term recovery.Capsaicin,a dietary irritant,is generally avoided during antibiotic therapy,but its mechanism remains unclear.To explore the effects of capsaicin on intestinal health during antibiotic administration,we conducted experiments in specifi c pathogen free(SPF)and germ-free(GF)mice and correlation analyses using 16S rRNA sequencing and nontargeted metabolomics to explore the protective role of the intestinal biological barrier.The results showed that additional supplementation of capsaicin under antibiotic exposure did not cause serious damage to the intestine,but had potential adverse effects on the structure,function,and metabolites of GM,including increasing the abundance of opportunistic pathogens(Mucispirillum and Aeromonas),enriching metabolic pathways(arachidonic acid metabolism and lipopolysaccharide biosynthesis),and metabolites associated with colon infl ammation(N-acetylhistamine).In the absence of GM barrier,the benefi cial function of capsaicin on the intestine was weakened and even induced adverse effects,suggesting that GM may have a certain mediating mechanism in the physiological function of capsaicin. 展开更多
关键词 Capsaicin Antibiotic exposure Gut microbiota Germ-free mice 16S rRNA Untargeted metabolomics
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