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1.
Nat Commun ; 11(1): 4844, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973204

RESUMO

Akkermansia muciniphila is a mucin-degrading bacterium commonly found in the human gut that promotes a beneficial effect on health, likely based on the regulation of mucus thickness and gut barrier integrity, but also on the modulation of the immune system. In this work, we focus in OgpA from A. muciniphila, an O-glycopeptidase that exclusively hydrolyzes the peptide bond N-terminal to serine or threonine residues substituted with an O-glycan. We determine the high-resolution X-ray crystal structures of the unliganded form of OgpA, the complex with the glycodrosocin O-glycopeptide substrate and its product, providing a comprehensive set of snapshots of the enzyme along the catalytic cycle. In combination with O-glycopeptide chemistry, enzyme kinetics, and computational methods we unveil the molecular mechanism of O-glycan recognition and specificity for OgpA. The data also contribute to understanding how A. muciniphila processes mucins in the gut, as well as analysis of post-translational O-glycosylation events in proteins.


Assuntos
Microbioma Gastrointestinal/fisiologia , Mucinas/metabolismo , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase/química , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase/metabolismo , Verrucomicrobia/metabolismo , Animais , Sítios de Ligação , Cristalografia por Raios X , Glicopeptídeos/química , Humanos , Mamíferos , Simulação de Acoplamento Molecular , Mucina-1/metabolismo , Polissacarídeos/química , Conformação Proteica , Alinhamento de Sequência , Verrucomicrobia/enzimologia
2.
Medicine (Baltimore) ; 99(39): e22273, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991426

RESUMO

BACKGROUND: Coronavirus disease (COVID-19) sparked global concern for its outbreak and pandemic. It caused severe respiratory tract infections and a significant proportion of patients with gastrointestinal symptoms. Several studies have investigated the intestinal flora of COVID-19. However, so far there has been no evidence demonstrating the evidence on the association of COVID-19 with intestinal flora through meta-analysis. A systematic and comprehensive understanding of their relationship is essential to provide public health prevention or treatment strategy. METHODS AND ANALYSIS: This systematic review and meta-analysis will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies (cohort studies, case-control, and cross-sectional studies) and clinical trials will be eligible. Studies eligible for inclusion must contain participants with COVID-19. Systematic searches will be conducted in PubMed, EMBASE, Cochrane Library, Ovid, EBSCO, World Health Organization COVID-19 database, China National Knowledge Internet, WanFang Data, Chinese Scientific and Technological Journal Database, and Chinese Biomedical Databases. A pre-designed search strategy of medical subject headings and free text terms for COVID-19 and intestinal flora will be used. Two reviewers will independently screen the titles and abstracts, followed by full-text screening. Discrepancies will be resolved by consensus with a third reviewer. The reviewers will then extract data from each eligible article based on PECOS (Population, Exposure, Comparator, Outcomes, and Study design). The risk of bias and quality of included studies will be assessed using an appropriate tool. A random-effects meta-analysis will be considered where there are sufficiently homogeneous studies; otherwise, a narrative synthesis will be conducted. Heterogeneity among studies will be assessed using I statistics. If substantial heterogeneity detected, subgroup analyses and meta-regression will be conducted to look for the potential causes. ETHICS AND DISSEMINATION: Ethical approval is not required as we will use data from published articles. Findings will be published in a peer-reviewed journal.PROSPERO registration number: CRD42020191640.


Assuntos
Infecções por Coronavirus/patologia , Microbioma Gastrointestinal/fisiologia , Pneumonia Viral/patologia , Betacoronavirus , Humanos , Estudos Observacionais como Assunto , Pandemias , Projetos de Pesquisa
3.
Nat Commun ; 11(1): 4457, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901017

RESUMO

Innate lymphoid cells (ILCs) and CD4+ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4+ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4+ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.


Assuntos
Ácidos Graxos Voláteis/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Interleucinas/biossíntese , Animais , Butiratos/imunologia , Butiratos/metabolismo , Butiratos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Citrobacter rodentium , Colite/imunologia , Colite/microbiologia , Colite/prevenção & controle , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/prevenção & controle , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Microbioma Gastrointestinal/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Técnicas In Vitro , Interleucinas/deficiência , Interleucinas/genética , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Regiões Promotoras Genéticas , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo
4.
Nat Commun ; 11(1): 4766, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958778

RESUMO

Germline telomere maintenance defects are associated with an increased incidence of inflammatory diseases in humans, yet whether and how telomere dysfunction causes inflammation are not known. Here, we show that telomere dysfunction drives pATM/c-ABL-mediated activation of the YAP1 transcription factor, up-regulating the major pro-inflammatory factor, pro-IL-18. The colonic microbiome stimulates cytosolic receptors activating caspase-1 which cleaves pro-IL-18 into mature IL-18, leading to recruitment of interferon (IFN)-γ-secreting T cells and intestinal inflammation. Correspondingly, patients with germline telomere maintenance defects exhibit DNA damage (γH2AX) signaling together with elevated YAP1 and IL-18 expression. In mice with telomere dysfunction, telomerase reactivation in the intestinal epithelium or pharmacological inhibition of ATM, YAP1, or caspase-1 as well as antibiotic treatment, dramatically reduces IL-18 and intestinal inflammation. Thus, telomere dysfunction-induced activation of the ATM-YAP1-pro-IL-18 pathway in epithelium is a key instigator of tissue inflammation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Inflamação/patologia , Telômero/patologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antibacterianos/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Caspase 1/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Criança , Colo/metabolismo , Colo/microbiologia , Colo/patologia , Gastroenteropatias/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-18/genética , Interleucina-18/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Mutantes , Fosforilação , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Transdução de Sinais , Telomerase/genética , Telomerase/metabolismo
5.
Medicine (Baltimore) ; 99(39): e22273, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: covidwho-811173

RESUMO

BACKGROUND: Coronavirus disease (COVID-19) sparked global concern for its outbreak and pandemic. It caused severe respiratory tract infections and a significant proportion of patients with gastrointestinal symptoms. Several studies have investigated the intestinal flora of COVID-19. However, so far there has been no evidence demonstrating the evidence on the association of COVID-19 with intestinal flora through meta-analysis. A systematic and comprehensive understanding of their relationship is essential to provide public health prevention or treatment strategy. METHODS AND ANALYSIS: This systematic review and meta-analysis will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies (cohort studies, case-control, and cross-sectional studies) and clinical trials will be eligible. Studies eligible for inclusion must contain participants with COVID-19. Systematic searches will be conducted in PubMed, EMBASE, Cochrane Library, Ovid, EBSCO, World Health Organization COVID-19 database, China National Knowledge Internet, WanFang Data, Chinese Scientific and Technological Journal Database, and Chinese Biomedical Databases. A pre-designed search strategy of medical subject headings and free text terms for COVID-19 and intestinal flora will be used. Two reviewers will independently screen the titles and abstracts, followed by full-text screening. Discrepancies will be resolved by consensus with a third reviewer. The reviewers will then extract data from each eligible article based on PECOS (Population, Exposure, Comparator, Outcomes, and Study design). The risk of bias and quality of included studies will be assessed using an appropriate tool. A random-effects meta-analysis will be considered where there are sufficiently homogeneous studies; otherwise, a narrative synthesis will be conducted. Heterogeneity among studies will be assessed using I statistics. If substantial heterogeneity detected, subgroup analyses and meta-regression will be conducted to look for the potential causes. ETHICS AND DISSEMINATION: Ethical approval is not required as we will use data from published articles. Findings will be published in a peer-reviewed journal.PROSPERO registration number: CRD42020191640.


Assuntos
Infecções por Coronavirus/patologia , Microbioma Gastrointestinal/fisiologia , Pneumonia Viral/patologia , Betacoronavirus , Humanos , Estudos Observacionais como Assunto , Pandemias , Projetos de Pesquisa
6.
Medicine (Baltimore) ; 99(37): e21950, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925728

RESUMO

INTRODUCTION: Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal (GI) symptoms, recently described as a disturbance of the brain-gut-microbiota (BGM) axis. To gain a better understanding of the mechanisms underlying the poorly understood etiology of IBS, we have designed a multifaceted study that aim to stratify the complex interaction and dysfunction between the brain, the gut, and the microbiota in patients with IBS. METHODS: Deep phenotyping data from patients with IBS (n = 100) and healthy age- (between 18 and 65) and gender-matched controls (n = 40) will be collected between May 2019 and December 2021. Psychometric tests, questionnaires, human biological tissue/samples (blood, faeces, saliva, and GI biopsies from antrum, duodenum, and sigmoid colon), assessment of gastric accommodation and emptying using transabdominal ultrasound, vagal activity, and functional and structural magnetic resonance imaging (MRI) of the brain, are included in the investigation of each participant. A subgroup of 60 patients with IBS-D will be further included in a 12-week low FODMAP dietary intervention-study to determine short and long-term effects of diet on GI symptoms, microbiota composition and functions, molecular GI signatures, cognitive, emotional and social functions, and structural and functional brain signatures. Deep machine learning, prediction tools, and big data analyses will be used for multivariate analyses allowing disease stratification and diagnostic biomarker detection. DISCUSSION: To our knowledge, this is the first study to employ unsupervised machine learning techniques and incorporate systems-based interactions between the central and the peripheral components of the brain-gut-microbiota axis at the levels of the multiomics, microbiota profiles, and brain connectome of a cohort of 100 patients with IBS and matched controls; study long-term safety and efficacy of the low-FODMAP diet on changes in nutritional status, gut microbiota composition, and metabolites; and to investigate changes in the brain and gut connectome after 12 weeks strict low-FODMAP-diet in patients with IBS. However, there are also limitations to the study. As a restrictive diet, the low-FODMAP diet carries risks of nutritional inadequacy and may foster disordered eating patterns. Strict FODMAP restriction induces a potentially unfavourable gut microbiota, although the health effects are unknown. TRIAL REGISTRATION NUMBER: NCT04296552 (ClinicalTrials.gov).


Assuntos
Dieta com Restrição de Carboidratos/métodos , Microbioma Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/dietoterapia , Síndrome do Intestino Irritável/microbiologia , Adolescente , Adulto , Idoso , Encéfalo/microbiologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Cognição/fisiologia , Feminino , Fermentação , Humanos , Síndrome do Intestino Irritável/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
7.
Chemosphere ; 254: 126891, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957291

RESUMO

Gut microbiota executes many beneficial functions. In this study, the relationship between gut microbiota and ovarian development in the swimming crab P. trituberculatus was explored for the first time. A total of 28 phyla and 422 genera were identified across all samples. However, 105 differential operational taxonomic units, and four differential phyla (Gemmatimonadetes, Actinobacteria, Firmicutes, Marinimicrobia_(SAR406_clade)) were identified. At the genus level, 42 differential genera were identified and 144 bacterial indicators were identified. A key finding was that the relative abundance of 139 indicator bacteria detected in the anisomycin-2 mg/kg group (AK group) was higher than that of blank group (BK group), control group (CK group), SP600125-15 mg/kg group (SK group). In addition, the relative abundance of three indicator bacteria (OTU_236, OTU_1395, OTU_552) detected in the SK group was higher than that of the BK, CK and AK groups. It was also found that the relative abundance of 20 differential genera (Methyloversatilis, Coprococcus_1, Erysipelotrichaceae_UCG_003, Rikenella, Corynebacterium, Ruminiclostridium, Fusicatenibacter, [Eubacterium]_ruminantium_group, Rikenellaceae_RC9_gut_group, Bifidobacterium, Lachnospiraceae_NK4A136_group, Ruminococcaceae_UCG_014, Christensenellaceae_R_7_group, uncultured_Bacteroidales_bacterium, Coprococcus_2, Desulfovibrio, Aggregatibacter, Ambiguous_taxa, Alloprevotella and Ruminococcaceae_NK4A214_group) in the SK, BK, CK, and AK group samples were increasing. These differential genera may reveal the relationship between gut microbial communities and ovarian development in P. trituberculatus after injection with the JNK pathway inhibitor SP600125 or the activator anisomycin. In summary, this study provides a new understanding into the relationship between gut microbiota and ovarian development in response to stimulation with inhibitor or activator.


Assuntos
Braquiúros/fisiologia , Microbioma Gastrointestinal/fisiologia , Animais , Bactérias/genética , Feminino , Microbioma Gastrointestinal/genética , Microbiota , RNA Ribossômico 16S/genética , Natação
8.
Nat Commun ; 11(1): 4120, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807798

RESUMO

Lysine acetylation (Kac), an abundant post-translational modification (PTM) in prokaryotes, regulates various microbial metabolic pathways. However, no studies have examined protein Kac at the microbiome level, and it remains unknown whether Kac level is altered in patient microbiomes. Herein, we use a peptide immuno-affinity enrichment strategy coupled with mass spectrometry to characterize protein Kac in the microbiome, which successfully identifies 35,200 Kac peptides from microbial or human proteins in gut microbiome samples. We demonstrate that Kac is widely distributed in gut microbial metabolic pathways, including anaerobic fermentation to generate short-chain fatty acids. Applying to the analyses of microbiomes of patients with Crohn's disease identifies 52 host and 136 microbial protein Kac sites that are differentially abundant in disease versus controls. This microbiome-wide acetylomic approach aids in advancing functional microbiome research.


Assuntos
Doença de Crohn/metabolismo , Microbioma Gastrointestinal/fisiologia , Lisina/metabolismo , Acetilação , Voluntários Saudáveis , Humanos , Análise Multivariada , Proteômica , Espectrometria de Massas em Tandem
9.
Medicine (Baltimore) ; 99(31): e21612, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756217

RESUMO

BACKGROUND: Emerging evidence indicates the role of gut microbiota in the development of cardiovascular diseases. Thus, gut microbiota is increasingly recognized as a potential therapeutic target of cardiovascular disease. However, the effects of gut microbiome-targeted therapies on cardiometabolic outcomes in children and adolescents remain unclear. METHODS: We plan to perform a systematic search from PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Two authors will independently select the relevant studies and extract data according to a previously defined data extraction sheet. We will use the Stata 14.0 statistical software and RevMan V.5.3 software to conduct data analyses. RESULTS AND CONCLUSION: The results of this study will be published in a peer-reviewed journal and provide more evidence for the application of gut microbiome-targeted therapies in children and adolescents for the intervention of cardiovascular risk factors in clinical practice. PROTOCOL REGISTRATION NUMBER: INPLASY202060050.


Assuntos
Doenças Cardiovasculares/epidemiologia , Suplementos Nutricionais , Probióticos/administração & dosagem , Simbióticos/administração & dosagem , Adolescente , Glicemia , Pressão Sanguínea , Criança , Pré-Escolar , Feminino , Microbioma Gastrointestinal/fisiologia , Hemoglobina A Glicada , Humanos , Lactente , Insulina/metabolismo , Lipídeos/sangue , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
10.
Nat Commun ; 11(1): 4322, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859898

RESUMO

Gut microbial and metabolite alterations have been linked to the pathogenesis of inflammatory bowel diseases. Here we perform a multi-omics microbiome and metabolite analysis of a longitudinal cohort of Crohn's disease patients undergoing autologous hematopoietic stem cell transplantation, and investigational therapy that induces drug free remission in a subset of patients. Via comparison of patients who responded and maintained remission, responded but experienced disease relapse and patients who did not respond to therapy, we identify shared functional signatures that correlate with disease activity despite the variability of gut microbiota profiles at taxonomic level. These signatures reflect the disease state when transferred to gnotobiotic mice. Taken together, the integration of microbiome and metabolite profiles from human cohort and mice improves the predictive modelling of disease outcome, and allows the identification of a network of bacteria-metabolite interactions involving sulfur metabolism as a key mechanism linked to disease activity in Crohn's disease.


Assuntos
Doença de Crohn/metabolismo , Doença de Crohn/microbiologia , Microbioma Gastrointestinal/fisiologia , Enxofre/metabolismo , Adolescente , Adulto , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Doença de Crohn/tratamento farmacológico , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Interleucina-10/genética , Masculino , Metagenoma , Camundongos , Camundongos Knockout , RNA Ribossômico 16S/genética , Indução de Remissão , Adulto Jovem
11.
Nat Commun ; 11(1): 4321, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859904

RESUMO

Bacterial colonization of the human intestine requires firm adhesion of bacteria to insoluble substrates under hydrodynamic flow. Here we report the molecular mechanism behind an ultrastable protein complex responsible for resisting shear forces and adhering bacteria to cellulose fibers in the human gut. Using single-molecule force spectroscopy (SMFS), single-molecule FRET (smFRET), and molecular dynamics (MD) simulations, we resolve two binding modes and three unbinding reaction pathways of a mechanically ultrastable R. champanellensis (Rc) Dockerin:Cohesin (Doc:Coh) complex. The complex assembles in two discrete binding modes with significantly different mechanical properties, with one breaking at ~500 pN and the other at ~200 pN at loading rates from 1-100 nN s-1. A neighboring X-module domain allosterically regulates the binding interaction and inhibits one of the low-force pathways at high loading rates, giving rise to a catch bonding mechanism that manifests under force ramp protocols. Multi-state Monte Carlo simulations show strong agreement with experimental results, validating the proposed kinetic scheme. These results explain mechanistically how gut microbes regulate cell adhesion strength at high shear stress through intricate molecular mechanisms including dual-binding modes, mechanical allostery and catch bonds.


Assuntos
Aderência Bacteriana/fisiologia , Microbioma Gastrointestinal/fisiologia , Fenômenos Mecânicos , Fenômenos Físicos , Bactérias , Aderência Bacteriana/genética , Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Trato Gastrointestinal/microbiologia , Técnicas de Inativação de Genes , Humanos , Cinética , Simulação de Dinâmica Molecular , Método de Monte Carlo , Ligação Proteica , Conformação Proteica , Imagem Individual de Molécula , Estresse Mecânico
12.
Nat Commun ; 11(1): 4236, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843654

RESUMO

The impact of commensal bacteria on the host arises from complex microbial-diet-host interactions. Mapping metabolic interactions in gut microbial communities is therefore key to understand how the microbiome influences the host. Here we use an interdisciplinary approach including isotope-resolved metabolomics to show that in Drosophila melanogaster, Acetobacter pomorum (Ap) and Lactobacillus plantarum (Lp) a syntrophic relationship is established to overcome detrimental host diets and identify Ap as the bacterium altering the host's feeding decisions. Specifically, we show that Ap uses the lactate produced by Lp to supply amino acids that are essential to Lp, allowing it to grow in imbalanced diets. Lactate is also necessary and sufficient for Ap to alter the fly's protein appetite. Our data show that gut bacterial communities use metabolic interactions to become resilient to detrimental host diets. These interactions also ensure the constant flow of metabolites used by the microbiome to alter reproduction and host behaviour.


Assuntos
Dieta , Drosophila melanogaster/microbiologia , Drosophila melanogaster/fisiologia , Microbioma Gastrointestinal/fisiologia , Acetobacter/crescimento & desenvolvimento , Acetobacter/metabolismo , Aminoácidos/deficiência , Aminoácidos/metabolismo , Animais , Apetite , Feminino , Preferências Alimentares , Interações entre Hospedeiro e Microrganismos , Ácido Láctico/metabolismo , Lactobacillus plantarum/crescimento & desenvolvimento , Lactobacillus plantarum/metabolismo , Redes e Vias Metabólicas , Metabolômica , Consórcios Microbianos , Reprodução
13.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(5): 516-520, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842435

RESUMO

Colorectal cancer is one of the most common malignant tumors of digestive tract. There are a large number of microorganisms in the digestive tract. Under normal physiological conditions, intestinal microorganisms can help with digestion and absorption, resist pathogen invasion and regulate the proliferation of intestinal mucosal cells. However, intestinal microflora imbalance will affect the intestinal microenvironment and intestinal cell function, and is closely related to the incidence and progression of colorectal cancer. Firstly, this paper introduces the changes of intestinal flora in patients with colorectal cancer, and then summarizes the mode of intestinal flora participating in the occurrence of colorectal cancer from the macro level. Then, we elaborate the involvement of intestinal flora in colorectal cancer from the aspects of cytokine-dependent chronic inflammation, DNA damage of intestinal epithelial cells, carcinogenic metabolites of intestinal flora and cellular enzymes, and changes of intestinal immune system. The pathogenesis of colorectal cancer provides a reference for further study of the pathogenesis of colorectal cancer. Finally, from the perspective of intestinal flora and colorectal cancer treatment, we analyze the significance of probiotics and bacterial flora transplantation for the treatment of colorectal cancer, and provide some new treatment ideas and methods that may be useful for the treatment of colorectal cancer.


Assuntos
Carcinogênese , Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal/fisiologia , Intestinos/microbiologia , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/terapia , Transplante de Microbiota Fecal , Humanos , Intestinos/patologia , Intestinos/fisiopatologia , Probióticos/uso terapêutico , Microambiente Tumoral/fisiologia
14.
Ecotoxicol Environ Saf ; 204: 111119, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32798757

RESUMO

The rapid spread of antibiotic resistance genes (ARGs) is a great challenge to the ecological safety and human health. The intestine of humans and animals is an important site for the increase and spread of ARGs due to the great diversity and abundance of microorganisms in the intestinal microecology. ARGs, including the intracellular (iARGs) and the extracellular (eARGs) ARGs, are usually introduced into the intestinal tract through the diet, and the iARGs are colonized and spread in the intestinal microbiota with the help of the host bacteria. However, whether the eARGs can enter the intestinal microorganisms in the absence of host bacteria is not known. Here, we show the transformation and the diffusion of the ampramycin resistance gene (Ap) carried by the free plasmid RK2 in the intestinal microbiota of mice. After two days of consecutive gavage with free RK2, the intracellular Ap gene increases from days 0-8 in the feces of mice, and has remained constant. Bacterial transformation happens in the small intestine, including proximal and distal jejuna and proximal and distal ilea, at the early stage (first two days), and the intracellular RK2 is diffused into the intestinal microbiota of mice by conjugation on days 2-8 day, which is based on the distribution of eARG and iARG and the mRNA expression levels of trbBp, trfAp, korA, korB, and trbA. The characteristics of ARGs susceptible microbiota for transformation are analyzed using 16s rRNA gene sequencing, transmission electron microscopy, and flow cytometric. The ingestion of RK2 affects the composition of intestinal microbiota especially for Proteobacteria, and the antibiotic residue promotes the increase in Escherichia coli. These findings are important to assess the risk of ARGs, especially the eARGs in the intestinal microecology.


Assuntos
Resistência Microbiana a Medicamentos/genética , Microbioma Gastrointestinal/fisiologia , Genes Bacterianos , Camundongos/microbiologia , Animais , Antibacterianos , Bactérias , Escherichia coli/efeitos dos fármacos , Fezes , Humanos , Intestinos , Microbiota , Plasmídeos , RNA Ribossômico 16S/genética
15.
Am J Gastroenterol ; 115(10): 1707-1715, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32852340

RESUMO

INTRODUCTION: Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. DISCUSSION: We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Ácido Gástrico/metabolismo , Inquéritos Epidemiológicos/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Adolescente , Adulto , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/estatística & dados numéricos , Fatores de Confusão Epidemiológicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Refluxo Gastroesofágico/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Azia/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Adulto Jovem
16.
PLoS One ; 15(8): e0237775, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813739

RESUMO

Nile tilapia, Oreochromis niloticus is the third most commonly farmed finfish species in the world, accounting for nearly 5% of global aquaculture production. In the past few decades much of the success of this species has been attributed to the development and distribution of Genetically Improved Farmed Tilapia (GIFT). Despite the increasing availability of GIFT, the productivity of small-scale farming remains highly variable, particularly in developing nations. Commercial fish-feed pellets can increase fish farm productivity; however, many small-scale farmers rely on other means of feeding fish due to the high cost and limited availability of commercial fish feed pellets. Therefore, understanding how locally-sourced feeds affect the production of GIFT is an important step towards improving feeding practices, particularly for farmers with low financial capital. This study used stable isotope analysis (SIA) and 16S rRNA gene sequencing to compare the effects of a locally-sourced vegetable-based diet and commercial pellet-based diets on the relative condition, nutrient assimilation patterns and gastrointestinal microbiota of GIFT. GIFT fed a locally-sourced diet were smaller, and in a significantly poorer condition than those fed with commercial fish feeds. SIA showed no differences in dietary carbon between the two diets; however, δ13C, poor fish condition and the abundance of specific bacterial taxa (of such as Fusobacteria) were correlated. SIA revealed that GIFT fed locally-sourced diets that predominantly consisted of vegetables were significantly enriched in δ15N despite a perceived lack of dietary protein. This enrichment suggests that GIFT fed a locally-sourced diet may be supplementing their diet via cannibalism, a behaviour representative of poor farming practice. Overall this study highlights the need to increase the availability of suitable GIFT feeds in developing nations. The development a low-cost feed alternative could improve the success of small-scale GIFT farmers in PNG, increasing both food and income security within the region.


Assuntos
Ração Animal , Animais Geneticamente Modificados/metabolismo , Aquicultura/métodos , Ciclídeos/metabolismo , Microbioma Gastrointestinal/fisiologia , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/microbiologia , Aquicultura/economia , Aquicultura/organização & administração , Canibalismo , Ciclídeos/genética , Ciclídeos/microbiologia , DNA Bacteriano/isolamento & purificação , Suplementos Nutricionais/economia , Eficiência Organizacional/economia , Fazendas/economia , Fazendas/organização & administração , New South Wales , Nutrientes/metabolismo , RNA Ribossômico 16S/genética
17.
PLoS One ; 15(8): e0237182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764797

RESUMO

Necrotizing enterocolitis is the most common gastrointestinal disorder in premature neonates. This disease is characterized by massive epithelial necrosis, gut barrier dysfunction and improper mucosal defense development. Studies have shown that probiotic administration can decrease NEC incidence and mortality. The proposed mechanisms of probiotics for the prevention of NEC are: promotion of intestinal development; improved barrier function through decreased apoptosis and improved mucin production; decreased expression of proinflammatory cytokines IL6, IL8, and TNFα, and modulation of microbiota dysbiosis in preterm infants. However, reported sepsis in the immunocompromised preterm host has deterred routine prophylactic administration of probiotics in the neonatal intensive care unit. We hypothesize that maternal administration of probiotics to pregnant mouse dams can recapitulate the beneficial effects observed in neonates fed with probiotics directly. We exposed pregnant mice to the probiotics and monitored the changes in the developing intestines of the offspring. Pregnant mice were fed daily with the probiotics Lactobacillus acidophilus and Bifidobacterium infantis (LB) from embryonic day15 to 2-week-old postnatally. Intraperitoneal administration of IL-1ß in the pups was used to model proinflammatory insults. Sera were collected at 2 weeks of age and evaluated for inflammatory cytokines by enzyme-linked-immunosorbent-assay and gut permeability by Fluorescein isothiocyanate-dextran tracer assay. Ileal tissues were collected for the evaluation of apoptosis and proliferation of the intestinal epithelium; as well as mucin and tight junction integrity at mucosal surface by immunofluorescent staining. We find that maternal LB exposure facilitated intestinal epithelial cell differentiation, prevented loss of mucin and preserved the intestinal integrity and barrier function and decreased serum levels of IL-1ß, TNF-α and IL-6 in the preweaned offsprings. in LB exposed pups. We demonstrate that maternal probiotic supplementation promotes gut maturation in developing offspring. This is potentially a safe alternative therapy to induce intestinal maturation and prevent prematurity-associated neonatal disorders.


Assuntos
Enterocolite Necrosante/prevenção & controle , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/crescimento & desenvolvimento , Exposição Materna , Probióticos/administração & dosagem , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/microbiologia , Bifidobacterium longum subspecies infantis , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/microbiologia , Enterocolite Necrosante/patologia , Fezes/microbiologia , Feminino , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Interleucina-1beta/administração & dosagem , Interleucina-1beta/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Lactobacillus acidophilus , Camundongos
18.
PLoS One ; 15(7): e0236936, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735609

RESUMO

The Roux-en-Y gastric bypass (RYGB) remains the most effective treatment for morbidly obese patients to lower body weight and improve glycemic control. There is recent evidence that the mycobiome (fungal microbiome) can aggravate disease severity in a number of diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and hepatitis; moreover, a dysbiotic fungal microbiota has been reported in the obese. We characterized fungal and bacterial microbial composition in fecal samples of 16 morbidly obese patients before and three months after RYGB surgery and compared with nine healthy controls. We found that RYGB surgery induced a clear alteration in structure and composition of the gut fungal and bacterial microbiota. Beta diversity analysis revealed significant differences in bacterial microbiota between obese patients before surgery and healthy controls (P < 0.005) and a significant, unidirectional shift in RYGB patients after surgery (P < 0.001 vs. before surgery). In contrast, there was no significant difference in fungal microbiota between groups but individually specific changes after RYGB surgery. Interestingly, RYGB surgery induced a significant reduction in fungal alpha diversity namely Chao1, Sobs, and Shannon diversity index (P<0.05, respectively) which contrasts the trend for uniform changes in bacteria towards increased richness and diversity post-surgery. We did not observe any inter-kingdom relations in RYGB patients but in the healthy control cohort and there were several correlations between fungi and bacteria and clinical parameters (P<0.05, respectively) that warrant further research. Our study identifies changes in intestinal fungal communities in RYGB patients that are distinct to changes in the bacterial microbiota.


Assuntos
Derivação Gástrica , Microbioma Gastrointestinal , Obesidade Mórbida , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , DNA Intergênico , Fezes/microbiologia , Feminino , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Genes Bacterianos , Genes Fúngicos , Humanos , Masculino , Metagenômica , Microbiota , Pessoa de Meia-Idade , Micobioma , Obesidade Mórbida/microbiologia , Obesidade Mórbida/cirurgia , Projetos Piloto , RNA Ribossômico 16S/genética
19.
Am J Gastroenterol ; 115(10): 1707-1715, 2020 10.
Artigo em Inglês | MEDLINE | ID: covidwho-732653

RESUMO

INTRODUCTION: Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. DISCUSSION: We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Ácido Gástrico/metabolismo , Inquéritos Epidemiológicos/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Adolescente , Adulto , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/estatística & dados numéricos , Fatores de Confusão Epidemiológicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Refluxo Gastroesofágico/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Azia/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Adulto Jovem
20.
Cell Rep ; 32(3): 107915, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32649864

RESUMO

Coronaviruses cause several human diseases, including severe acute respiratory syndrome. The global coronavirus disease 2019 (COVID-19) pandemic has become a huge threat to humans. Intensive research on the pathogenic mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed-notably to identify potential drug targets. Clinical studies of patients with COVID-19 have shown that gastrointestinal disorders appear to precede or follow the respiratory symptoms. Here, we review gastrointestinal disorders in patients with COVID-19, suggest hypothetical mechanisms leading to gut symptoms, and discuss the potential consequences of gastrointestinal disorders on the outcome of the disease. Lastly, we discuss the role of the gut microbiota during respiratory viral infections and suggest that targeting gut dysbiosis may help to control the pathogenesis of COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Gastroenteropatias/patologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/patologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Betacoronavirus/fisiologia , Disbiose/tratamento farmacológico , Disbiose/patologia , Gastroenteropatias/virologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/virologia , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Síndrome Respiratória Aguda Grave/virologia
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