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1.
Medicine (Baltimore) ; 99(40): e22442, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019428

RESUMO

Delivery methods during childbirth and their related gut microbiota profiles have important impacts on health later in life, they can contribute to the development of diseases such as obesity, whose highest prevalence rate is found among the Mexican child population. Coincidentally, Mexico has one of the highest global average annual rate increase in cesarean births (C-section). Since Mexico leads the world in childhood obesity, studying the relationship between childbirth delivery methods and gut microbiota profiles in this vulnerable population may be used to identify early risk factors for obesity in other developed and developing countries. The objective of this study is to determine the association between child delivery method and gut microbiota profiles in healthy Mexican newborns.Fecal samples of 57 term infants who participated in a randomized clinical trial in 2013 to study the safety of Agave fructans in newborns, were used in this study. DNA samples were extracted and used to characterize the microbiota composition using high-throughput 16S rRNA gene sequencing. The samples were further divided based on childbirth delivery method, as well as early diet. Gut microbiota profiles were determined and analyzed using cluster analysis followed by multiple correspondence analysis.An unusual high abundance of Proteobacteria was found in the gut microbiota of all Mexican infants studied, regardless of delivery method. Feces from infants born by C-section had low levels of Bacteroidetes, high levels of Firmicutes, especially Clostridium and Enterococcus, and a strikingly high ratio of Firmicutes/Bacteroidetes (F:B). Profiles enriched in Bacteroidetes and low F:B ratios, were strongly associated with vaginal delivery.The profile of gut microbiota associated with feces from Mexican infants born by C-section, may be added to the list of boosting factors for the worrying obesity epidemic in Mexico.


Assuntos
Cesárea/estatística & dados numéricos , Microbioma Gastrointestinal , Obesidade/epidemiologia , Cesárea/efeitos adversos , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Fatores de Risco
2.
BMC Infect Dis ; 20(1): 659, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894092

RESUMO

BACKGROUND: Diarrheagenic Escherichia coli (DEC) are among the leading pathogens associated with endemic diarrhea in low income countries. Yet, few epidemiological studies have focused the contribution of enterohemorrhagic E. coli (EHEC), enteroinvasive E. coli (EIEC) and diffusely adherent E. coli (DAEC). METHODS: We assessed the contribution of EHEC, EIEC and DAEC isolated from stool samples from a case-control study conducted in children aged < 5 years in Southern Mozambique between December 2007 and November 2012. The isolates were screened by conventional PCR targeting stx1 and stx2 (EHEC), ial and ipaH (EIEC), and daaE (DAEC) genes. RESULTS: We analyzed 297 samples from cases with less-severe diarrhea (LSD) matched to 297 controls, and 89 samples from cases with moderate-to-severe diarrhea (MSD) matched to 222 controls, collected between November 3, 2011 and November 2, 2012. DEC were more common among LSD cases (2.7%, [8/297] of cases vs. 1.3% [4/297] of controls; p = 0.243]) than in MSD cases (0%, [0/89] of cases vs. 0.4%, [1/222] of controls; p = 1.000). Detailed analysis revealed low frequency of EHEC, DAEC or EIEC and no association with diarrhea in all age strata. Although the low frequency, EIEC was predominant in LSD cases aged 24-59 months (4.1% for cases vs. 0% for controls), followed by DAEC in similar frequency for cases and controls in infants (1.9%) and lastly EHEC from one control. Analysis of a subset of samples from previous period (December 10, 2007 and October 31, 2011) showed high frequency of DEC in controls compared to MSD cases (16.2%, [25/154] vs. 11.9%, [14/118], p = 0.383, respectively). Among these, DAEC predominated, being detected in 7.7% of cases vs. 17.6% of controls aged 24-59 months, followed by EIEC in 7.7% of cases vs. 5.9% of controls for the same age category, although no association was observed. EHEC was detected in one sample from cases and two from controls. CONCLUSIONS: Our data suggests that although EHEC, DAEC and EIEC are less frequent in endemic diarrhea in rural Mozambique, attention should be given to their transmission dynamics (e.g. the role on sporadic or epidemic diarrhea) considering that the role of asymptomatic individuals as source of dissemination remains unknown.


Assuntos
Diarreia/epidemiologia , Escherichia coli Êntero-Hemorrágica/genética , Infecções por Escherichia coli/epidemiologia , Saúde da População Rural , Estudos de Casos e Controles , Pré-Escolar , Diarreia/microbiologia , Doenças Endêmicas , Escherichia coli Êntero-Hemorrágica/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Moçambique/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , População Rural
3.
Nat Commun ; 11(1): 4822, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973149

RESUMO

Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.


Assuntos
Acetato de Abiraterona/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Verrucomicrobia/efeitos dos fármacos , Acetato de Abiraterona/metabolismo , Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/farmacologia , Androgênios/metabolismo , Bactérias/metabolismo , Fezes/microbiologia , Humanos , Masculino , RNA Ribossômico 16S/genética , Verrucomicrobia/genética , Verrucomicrobia/metabolismo , Vitamina K 2/metabolismo , Vitamina K 2/farmacologia
4.
Medicine (Baltimore) ; 99(39): e22298, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991434

RESUMO

RATIONALE: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model. PATIENT CONCERNS: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection. DIAGNOSES: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis. INTERVENTIONS: The patient was treated with a total of 4 individual courses of FMT. OUTCOMES: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors. LESSONS: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.


Assuntos
Transplante de Microbiota Fecal/métodos , Hemorragia Gastrointestinal/terapia , Proctite/etiologia , Lesões por Radiação/complicações , Assistência ao Convalescente , Doença Crônica , Colonoscopia/métodos , Diarreia/etiologia , Fezes/microbiologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Proctite/diagnóstico , Proctite/patologia , RNA Ribossômico 16S/genética , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/patologia , Doadores de Tecidos , Resultado do Tratamento
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(8): 1328-1334, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32867445

RESUMO

Objective: To understand the characteristics and differences of diarrhea-related symptoms caused by different pathogens, and the clinical features of various pathogens causing diarrhea. Methods: Etiology surveillance program was conducted among 20 provinces of China from 2010 to 2016. The acute diarrhea outpatients were collected from clinics or hospitals. A questionnaire was used to survey demographics and clinical features. VFeces samples were taken for laboratory detection of 22 common diarrhea pathogens, to detect and analyze the clinical symptom pattern characteristics of the patient's. Results: A total of 38 950 outpatients were enrolled from 20 provinces of China. The positive rates of Rotavirus and Norovirus were the highest among the five diarrhea-causing viruses (Rotavirus: 18.29%, Norovirus: 13.06%). In the isolation and culture of 17 diarrhea-causing bacterial, Escherichia coli showed the highest positive rates (6.25%). The clinical features of bacterial diarrhea and viral diarrhea were mainly reflected in the results of fecal traits and routine examination, but pathogenic Vibrio infection was similar to viral diarrhea. Conclusion: Infectious diarrhea presents different characteristics due to various symptoms which can provide a basis for clinical diagnosis.


Assuntos
Disenteria/microbiologia , Disenteria/virologia , Vigilância da População , China/epidemiologia , Disenteria/epidemiologia , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Fezes/virologia , Humanos , Norovirus/isolamento & purificação , Rotavirus/isolamento & purificação
6.
Nat Commun ; 11(1): 4635, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934239

RESUMO

Providing insight into one's health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, we introduce the Gut Microbiome Health Index (GMHI), a biologically-interpretable mathematical formula for predicting the likelihood of disease independent of the clinical diagnosis. GMHI is formulated upon 50 microbial species associated with healthy gut ecosystems. These species are identified through a multi-study, integrative analysis on 4347 human stool metagenomes from 34 published studies across healthy and 12 different nonhealthy conditions, i.e., disease or abnormal bodyweight. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of disease presence (or absence) compared to α-diversity indices. Validation on 679 samples from 9 additional studies results in a balanced accuracy of 73.7% in distinguishing healthy from non-healthy groups. Our findings suggest that gut taxonomic signatures can predict health status, and highlight how data sharing efforts can provide broadly applicable discoveries.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Nível de Saúde , Bactérias/classificação , Bactérias/genética , Fezes/microbiologia , Humanos , Metagenoma , Microbiota
7.
BMC Infect Dis ; 20(1): 682, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942989

RESUMO

BACKGROUND: Enterobacter cloacae species is responsible for nosocomial outbreaks in vulnerable patients in neonatal intensive care units (NICU). The environment can constitute the reservoir and source of infection in NICUs. Herein we report the impact of preventive measures implemented after an Enterobacter cloacae outbreak inside a NICU. METHODS: This retrospective study was conducted in one level 3 NICU in Lyon, France, over a 6 year-period (2012-2018). After an outbreak of Enterobacter cloacae infections in hospitalized neonates in 2013, several measures were implemented including intensive biocleaning and education of medical staff. Clinical and microbiological characteristics of infected patients and evolution of colonization/infection with Enterobacter spp. in this NICU were retrieved. Moreover, whole genome sequencing was performed on 6 outbreak strains. RESULTS: Enterobacter spp. was isolated in 469 patients and 30 patients developed an infection including 2 meningitis and 12 fatal cases. Preventive measures and education of medical staff were not associated with a significant decrease in patient colonisation but led to a persistent decreased use of cephalosporin in the NICU. Infection strains were genetically diverse, supporting the hypothesis of multiple hygiene defects rather than the diffusion of a single clone. CONCLUSIONS: Grouped cases of infections inside one setting are not necessarily related to a single-clone outbreak and could reveal other environmental and organisational problematics. The fight against implementation and transmission of Enterobacter spp. in NICUs remains a major challenge.


Assuntos
Enterobacter cloacae/patogenicidade , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/prevenção & controle , Controle de Infecções/métodos , Surtos de Doenças/prevenção & controle , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , França , Humanos , Higiene , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Estudos Retrospectivos , Sequenciamento Completo do Genoma
8.
Chemosphere ; 258: 127392, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947654

RESUMO

Discharge of urban stormwater containing organic matter, heavy metals and sometime human feces, to the natural aquatic reservoirs without any treatment is not only an environmental problem. It can lead to prevalence of antibiotic resistant bacteria in stormwater systems and transmission of antibiotic resistance genes to the environment. We performed antibiotic resistome identification and virus detection in stormwater samples from Stockholm, using publicly available metagenomic sequencing MinION data. A MinION platform offers low-cost, precise environmental metagenomics analysis. 37 groups of antibiotic resistant bacteria (ARB), 11 resistance types with 26 resistance mechanisms - antibiotic resistance genes (ARGs) giving tolerance to the aminoglycoside, beta-lactams, fosmidomycin, MLS, multidrug and vancomycin were identified using ARGpore pipeline. The majority of the identified bacteria species were related to the natural environment such as soil and were not dangerous to human. Alarmingly, human pathogenic bacteria carrying resistance to antibiotics currently used against them (Bordetella resistant to macrolides and multidrug resistant Propionibacterium avidum) were also found in the samples. Most abundant viruses identified belonged to Caudovirales and Herpesvirales and they were not carrying ARGs. Unlike the virome, resistome and ARB were not unique for stormwater sampling points. This results underline the need for extensive monitoring of the microbial community structure in the urban stormwater systems to assess antimicrobial resistance spread.


Assuntos
Farmacorresistência Bacteriana/genética , Metagenoma , Bactérias/efeitos dos fármacos , Monitoramento Ambiental , Fezes/microbiologia , Genes Bacterianos/efeitos dos fármacos , Humanos , Macrolídeos , Metagenômica/métodos , Microbiota/efeitos dos fármacos , Águas Residuárias/microbiologia , beta-Lactamas
9.
Medicine (Baltimore) ; 99(35): e21488, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871870

RESUMO

BACKGROUND: Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors. Exposure to protein pump inhibitors (PPIs) was recently found to be associated with an increased risk for subsequent diagnosis of celiac disease. We aimed to investigate potential mechanisms for this link by examining the relationship between PPI use and gluten-related immune responses in the context of changes in gut microbiome. METHODS: We performed a post hoc analysis of blood and fecal samples from a recent randomized trial in order to assess the potential association between PPI use and development of celiac disease serology in conjunction with alterations in gastrointestinal microbial composition. The study included 12 healthy participants who were administered a PPI (Omeprazole; 40 mg twice daily) for 4 or 8 weeks. RESULTS: The analysis did not reveal an overall significant change in levels of serologic markers of celiac disease for the study cohort in response to PPI treatment. However, one individual developed a marked increase in the celiac disease-specific autoantibody response to transglutaminase 2 in conjunction with enhanced immune reactivity to gluten during the trial. Genotyping revealed positivity for the celiac disease-associated HLA-DQ2 and -DQ8 alleles. Furthermore, the observed elevation in antibody responses was closely associated with a sharp increase in fecal abundance of bacteria of the order Actinomycetales. CONCLUSIONS: The results of this exploratory analysis support further investigation of molecular mechanisms involved in the contribution of PPIs to celiac disease risk through the potential enhancement of gluten immunopathology and changes in gut microbial population.


Assuntos
Doença Celíaca/sangue , Doença Celíaca/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Actinomycetales/crescimento & desenvolvimento , Adulto , Alelos , Doença Celíaca/epidemiologia , Doença Celíaca/metabolismo , Fezes/microbiologia , Feminino , Proteínas de Ligação ao GTP/sangue , Proteínas de Ligação ao GTP/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Genótipo , Glutens/efeitos adversos , Glutens/imunologia , Antígenos HLA-DQ/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Prevalência , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Transglutaminases/sangue , Transglutaminases/efeitos dos fármacos
10.
Mikrobiyol Bul ; 54(3): 368-377, 2020 Jul.
Artigo em Turco | MEDLINE | ID: mdl-32755514

RESUMO

Clostridioides difficile, a gram-positive, anaerobic, spore forming bacillus known as Clostridium difficile according to the previous taxonomy, is the most important agent of antibiotic-associated diarrhea. C.difficile infections have become a major health problem for many countries. The rate of antimicrobial resistant C.difficile isolates is rapidly increasing all around the world. Yet there is limited data on this subject in our country. The aim of this study was to determine the antimicrobial susceptibility profiles of C.difficile strains isolated from stool samples in Marmara University Pendik Training and Research Hospital Microbiology Laboratory. A total of 93 toxigenic C.difficile, defined by serological and molecular techniques, were included in this study. Antimicrobial susceptibility profiles of isolates were determined by using agar dilution method according to the Clinical and Laboratory Standards Institute (CLSI; M11-A7). The following antimicrobials commonly used for the treatment of C.difficile infections or applied previously in C.difficile epidemiological studies were tested: metronidazole, vancomycin, meropenem, ceftriaxone, ampicillin-sulbactam, clindamycin, erythromycin, moxifloxacin, tetracycline, doxycycline, tigecycline and linezolid. The minimum inhibitory concentration (MIC) results were interpreted according to the breakpoints described by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoints recommended by CLSI were applied for ceftriaxone, clindamycin, tetracycline and moxifloxacin since there were no EUCAST breakpoints for these antimicrobials. MIC50 and MIC90 values were determined for three antimicrobials (linezolid, erythromycin, doxycycline) whose breakpoints were not described by EUCAST or CLSI guidelines. All isolates were susceptible to metronidazole, vancomycin, ampicillin-sulbactam, meropenem and tetracycline. Susceptibility to ceftriaxone, clindamycin and moxifloxacin was found in 58.1%, 35.5% and 20.4% of the isolates, respectively. MIC50 and MIC90 values of tigecycline, erythromycin linezolid, doxycycline were 0.125-0.25 mg/L, 1-2 mg/L, 2-2 mg/L, 0.062- 0.125 mg/L, respectively. This study shows the current antimicrobial susceptibility patterns of C.difficile isolates in our hospital and will also be the reference data for clinical laboratories in our country where anaerobic culture and susceptibility tests are not performed in routine practice. In conclusion, two main antimicrobial agents commonly used in the treatment of C.difficile infections, metronidazole and vancomycin, seem to be effective. However, high resistance rates against to the certain tested antimicrobials highlight the need for further surveillance to monitor the emergence of resistance.


Assuntos
Antibacterianos , Clostridium difficile , Antibacterianos/farmacologia , Clostridium difficile/efeitos dos fármacos , Fezes/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Turquia , Universidades
11.
PLoS Negl Trop Dis ; 14(8): e0008440, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745137

RESUMO

Invasive Non-typhoidal Salmonella (iNTS) disease is a major public health challenge, especially in Sub-Saharan Africa (SSA). In Kenya, mortality rates are high (20-25%) unless prompt treatment is instituted. The most common serotypes are Salmonella enterica serotype Typhimurium (S. Typhimurium) and Salmonella enterica serotype Enteritidis (S. Enteritidis). In a 5 year case-control study in children residing in the Mukuru informal settlement in Nairobi, Kenya, a total of 4201 blood cultures from suspected iNTS cases and 6326 fecal samples from age-matched controls were studied. From the laboratory cultures we obtained a total of 133 S. Typhimurium isolates of which 83(62.4%) came from cases (53 blood and 30 fecal) and 50(37.6%) from controls (fecal). A total of 120 S. Enteritidis consisted of 70(58.3%) from cases (43 blood and 27 fecal) and 50(41.7%) from controls (fecal). The S. Typhimurium population fell into two distinct ST19 lineages constituting 36.1%, as well as ST313 lineage I (27.8%) and ST313 lineage II (36.1%) isolates. The S. Enteritidis isolates fell into the global epidemic lineage (46.6%), the Central/Eastern African lineage (30.5%), a novel Kenyan-specific lineage (12.2%) and a phylogenetically outlier lineage (10.7%). Detailed phylogenetic analysis revealed a high level of relatedness between NTS from blood and stool originating from cases and controls, indicating a common source pool. Multidrug resistance was common throughout, with 8.5% of such isolates resistant to extended spectrum beta lactams. The high rate of asymptomatic carriage in the population is a concern for transmission to vulnerable individuals and this group could be targeted for vaccination if an iNTS vaccine becomes available.


Assuntos
Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Salmonella enteritidis/genética , Estudos de Casos e Controles , Pré-Escolar , Farmacorresistência Bacteriana Múltipla/genética , Fezes/microbiologia , Feminino , Genótipo , Humanos , Lactente , Quênia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Filogenia , Áreas de Pobreza , Infecções por Salmonella/sangue , Salmonella enteritidis/isolamento & purificação
12.
BMC Bioinformatics ; 21(1): 345, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778056

RESUMO

BACKGROUND: Comparing the composition of microbial communities among groups of interest (e.g., patients vs healthy individuals) is a central aspect in microbiome research. It typically involves sequencing, data processing, statistical analysis and graphical display. Such an analysis is normally obtained by using a set of different applications that require specific expertise for installation, data processing and in some cases, programming skills. RESULTS: Here, we present SHAMAN, an interactive web application we developed in order to facilitate the use of (i) a bioinformatic workflow for metataxonomic analysis, (ii) a reliable statistical modelling and (iii) to provide the largest panel of interactive visualizations among the applications that are currently available. SHAMAN is specifically designed for non-expert users. A strong benefit is to use an integrated version of the different analytic steps underlying a proper metagenomic analysis. The application is freely accessible at http://shaman.pasteur.fr/ , and may also work as a standalone application with a Docker container (aghozlane/shaman), conda and R. The source code is written in R and is available at https://github.com/aghozlane/shaman . Using two different datasets (a mock community sequencing and a published 16S rRNA metagenomic data), we illustrate the strengths of SHAMAN in quickly performing a complete metataxonomic analysis. CONCLUSIONS: With SHAMAN, we aim at providing the scientific community with a platform that simplifies reproducible quantitative analysis of metagenomic data.


Assuntos
Classificação , Internet , Metagenômica/métodos , Software , Estatística como Assunto , Interface Usuário-Computador , Líquidos Corporais/microbiologia , Pré-Escolar , Fezes/microbiologia , Humanos , Metagenoma , Microbiota , RNA Ribossômico 16S/genética , Fluxo de Trabalho
13.
BMC Infect Dis ; 20(1): 557, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736605

RESUMO

BACKGROUND: Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. METHODS: This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 µg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. RESULTS: Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07-69.88, p = 0.01). CONCLUSIONS: High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Fezes/microbiologia , beta-Lactamases/biossíntese , Adolescente , Adulto , Antibacterianos/uso terapêutico , Ceftazidima , Estudos Transversais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta , Tanzânia/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
14.
PLoS Negl Trop Dis ; 14(8): e0008536, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804926

RESUMO

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.


Assuntos
Diarreia/diagnóstico , Diarreia/epidemiologia , Disenteria Bacilar/diagnóstico , Disenteria Bacilar/epidemiologia , Bangladesh/epidemiologia , Brasil/epidemiologia , Diarreia/microbiologia , Disenteria , Disenteria Bacilar/microbiologia , Fezes/microbiologia , Feminino , Humanos , Incidência , Índia/epidemiologia , Lactente , Recém-Nascido , Intestinos , Masculino , Nepal/epidemiologia , Paquistão , Peru/epidemiologia , Prevalência , Shigella/genética , Shigella/isolamento & purificação , África do Sul/epidemiologia , Tanzânia/epidemiologia
15.
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
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(5): 509-515, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842434

RESUMO

Fecal microbiota transplant (FMT) has become an effective method for the treatment of recurrent C. difficile infection. In addition, it has shown certain effects in other diseases inside and outside the intestine. A large number of clinical trials have been carried out. However, there is still lack of uniform standard for strategies of FMT. In this paper, we discussed the current hot and controversial issues of FMT from the aspects of indication, donor screening, fecal suspension quality control, methodology, follow-up and efficacy judgment, treatment of adverse reaction and ethical supervision based on our team's clinical experience.


Assuntos
Infecções por Clostridium/terapia , Clostridium difficile/isolamento & purificação , Transplante de Microbiota Fecal/métodos , Seleção do Doador , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/normas , Fezes/microbiologia , Humanos , Resultado do Tratamento
17.
Life Sci ; 259: 118200, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758621

RESUMO

AIMS: Diet is one of the factors affecting the pathogenicity of Helicobacter pylori (H. pylori) infection. Choline is a dietary component that is crucial for normal cellular function. However, choline intake imbalance can lead to liver injury, inflammation, and changes of the gut microbiota composition. The study aimed to explore the effects of choline supplementation on liver biology, gut microbiota, and inflammation in H. pylori-infected mice. MAIN METHODS: Liver function was detected by biochemical and histopathological analysis. Serum inflammatory markers were measured using ELISA. Fecal microbial profiles were determined via 16S rRNA sequencing. KEY FINDINGS: The results showed that choline supplementation decreased serum LDL level, while increased the activities of serum AST and ALT in normal BALB/c mice. Besides, choline also reduced hepatic SOD and GSH-Px activities, and elevated hepatic MDA level of H. pylori-infected mice. Moreover, choline markedly enhanced the concentrations of inflammatory factors including LPS, CRP, IL-6, TNF-α, and CXCL1 in H. pylori-infected mice. Meanwhile, choline and H. pylori cotreatment altered the richness and diversity of the mice gut microbiota, and increased the relative abundance of Escherichia_Shigella, which had a significant positive correlation with the levels of LPS, CRP, IL-6, TNF-α and CXCL1. SIGNIFICANCE: Our data suggest, for the first time, that choline can aggravate H. pylori-induced inflammation, which may be associated with the alterations of gut microbiota. This study may provide novel insights into the possible effects of food-derived choline on H. pylori infection-related diseases.


Assuntos
Colina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Fígado/efeitos dos fármacos , Animais , LDL-Colesterol/sangue , Dieta , Fezes/microbiologia , Feminino , Infecções por Helicobacter/patologia , Inflamação/sangue , Fígado/enzimologia , Fígado/patologia , Testes de Função Hepática , Camundongos , Camundongos Endogâmicos BALB C , RNA Ribossômico 16S/genética
18.
Virology ; 548: 200-212, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32763491

RESUMO

The intestinal microbiota is crucial to intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) is high pathogenic to intestines, causing diarrhea, even death in piglets. To investigate the detailed relationship between PEDV infection and intestinal microbiota, the composition and distribution of intestinal microbiota from pigs were first analyzed using 16S rRNA sequencing technology. The results demonstrated that the composition and distribution of microbes in different intestinal segments were quite similar between 1-week-old and 2-week-old piglets but different from 4-week-old (weaned) piglets. Then piglets at different ages were inoculated with PEDV. The results showed that the 1-week-old piglets exhibited the most severe pathogenicity comparing to the other age groups. Further investigations indicated that Lactobacillus, Escherichia coli, and Lactococcus in the intestinal microbiota of piglets were significantly changed by PEDV infection. These results strengthen our understanding of viruses influencing intestinal microbes and remind us of the potential association between PEDV and intestinal microbes.


Assuntos
Infecções por Coronavirus/virologia , Microbioma Gastrointestinal , Vírus da Diarreia Epidêmica Suína/fisiologia , Doenças dos Suínos/virologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Infecções por Coronavirus/microbiologia , Fezes/microbiologia , Intestinos/microbiologia , Vírus da Diarreia Epidêmica Suína/genética , Suínos , Doenças dos Suínos/microbiologia
19.
PLoS One ; 15(8): e0236944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745090

RESUMO

Gut dysbiosis has been implicated in the pathophysiology of a growing number of non-communicable diseases. High through-put sequencing technologies and short chain fatty acid (SCFA) profiling enables surveying of the composition and function of the gut microbiota and provide key insights into host-microbiome interactions. However, a methodological problem with analyzing stool samples is that samples are treated and stored differently prior to submission for analysis potentially influencing the composition of the microbiota and its metabolites. In the present study, we simulated the sample acquisition of a large-scale study, in which stool samples were stored for up to two days in the fridge or at room temperature before being handed over to the hospital. To assess the influence of time and temperature on the microbial community and on SCFA composition in a controlled experimental setting, the stool samples of 10 individuals were exposed to room and fridge temperatures for 24 and 48 hours, respectively, and analyzed using 16S rRNA gene amplicon sequencing, qPCR and nuclear magnetic resonance spectroscopy. To best of our knowledge, this is the first study to investigate the influence of storage time and temperature on the absolute abundance of methanogens, and of Lactobacillus reuteri. The results indicate that values obtained for methanogens, L. reuteri and total bacteria are still representative even after storage for up to 48 hours at RT (20°C) or 4°C. The overall microbial composition and structure appeared to be influenced more by laboratory errors introduced during sample processing than by the actual effects of temperature and time. Although microbial activity was demonstrated by elevated SCFA at both 4°C and RT, SCFAs ratios were more stable over the different conditions and may be considered as long as samples are come from similar storage conditions.


Assuntos
Fezes/química , Fezes/microbiologia , Manejo de Espécimes/métodos , Adulto , Bactérias/genética , Disbiose/microbiologia , Ácidos Graxos Voláteis/análise , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Microbiota , RNA Ribossômico 16S/genética , Temperatura , Fatores de Tempo
20.
Cochrane Database Syst Rev ; 8: CD013359, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853411

RESUMO

BACKGROUND: Every year, at least one million children become ill with tuberculosis and around 200,000 children die. Xpert MTB/RIF and Xpert Ultra are World Health Organization (WHO)-recommended rapid molecular tests that simultaneously detect tuberculosis and rifampicin resistance in adults and children with signs and symptoms of tuberculosis, at lower health system levels. To inform updated WHO guidelines on molecular assays, we performed a systematic review on the diagnostic accuracy of these tests in children presumed to have active tuberculosis. OBJECTIVES: Primary objectives • To determine the diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for (a) pulmonary tuberculosis in children presumed to have tuberculosis; (b) tuberculous meningitis in children presumed to have tuberculosis; (c) lymph node tuberculosis in children presumed to have tuberculosis; and (d) rifampicin resistance in children presumed to have tuberculosis - For tuberculosis detection, index tests were used as the initial test, replacing standard practice (i.e. smear microscopy or culture) - For detection of rifampicin resistance, index tests replaced culture-based drug susceptibility testing as the initial test Secondary objectives • To compare the accuracy of Xpert MTB/RIF and Xpert Ultra for each of the four target conditions • To investigate potential sources of heterogeneity in accuracy estimates - For tuberculosis detection, we considered age, disease severity, smear-test status, HIV status, clinical setting, specimen type, high tuberculosis burden, and high tuberculosis/HIV burden - For detection of rifampicin resistance, we considered multi-drug-resistant tuberculosis burden • To compare multiple Xpert MTB/RIF or Xpert Ultra results (repeated testing) with the initial Xpert MTB/RIF or Xpert Ultra result SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the International Standard Randomized Controlled Trials Number (ISRCTN) Registry up to 29 April 2019, without language restrictions. SELECTION CRITERIA: Randomized trials, cross-sectional trials, and cohort studies evaluating Xpert MTB/RIF or Xpert Ultra in HIV-positive and HIV-negative children younger than 15 years. Reference standards comprised culture or a composite reference standard for tuberculosis and drug susceptibility testing or MTBDRplus (molecular assay for detection of Mycobacterium tuberculosis and drug resistance) for rifampicin resistance. We included studies evaluating sputum, gastric aspirate, stool, nasopharyngeal or bronchial lavage specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), fine needle aspirates, or surgical biopsy tissue (lymph node tuberculosis). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality using the Quality Assessment of Studies of Diagnostic Accuracy - Revised (QUADAS-2). For each target condition, we used the bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We assessed certainty of evidence using the GRADE approach. MAIN RESULTS: For pulmonary tuberculosis, 299 data sets (68,544 participants) were available for analysis; for tuberculous meningitis, 10 data sets (423 participants) were available; for lymph node tuberculosis, 10 data sets (318 participants) were available; and for rifampicin resistance, 14 data sets (326 participants) were available. Thirty-nine studies (80%) took place in countries with high tuberculosis burden. Risk of bias was low except for the reference standard domain, for which risk of bias was unclear because many studies collected only one specimen for culture. Detection of pulmonary tuberculosis For sputum specimens, Xpert MTB/RIF pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 64.6% (55.3% to 72.9%) (23 studies, 493 participants; moderate-certainty evidence) and 99.0% (98.1% to 99.5%) (23 studies, 6119 participants; moderate-certainty evidence). For other specimen types (nasopharyngeal aspirate, 4 studies; gastric aspirate, 14 studies; stool, 11 studies), Xpert MTB/RIF pooled sensitivity ranged between 45.7% and 73.0%, and pooled specificity ranged between 98.1% and 99.6%. For sputum specimens, Xpert Ultra pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 72.8% (64.7% to 79.6%) (3 studies, 136 participants; low-certainty evidence) and 97.5% (95.8% to 98.5%) (3 studies, 551 participants; high-certainty evidence). For nasopharyngeal specimens, Xpert Ultra sensitivity (95% CI) and specificity (95% CI) were 45.7% (28.9% to 63.3%) and 97.5% (93.7% to 99.3%) (1 study, 195 participants). For all specimen types, Xpert MTB/RIF and Xpert Ultra sensitivity were lower against a composite reference standard than against culture. Detection of tuberculous meningitis For cerebrospinal fluid, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 54.0% (95% CI 27.8% to 78.2%) (6 studies, 28 participants; very low-certainty evidence) and 93.8% (95% CI 84.5% to 97.6%) (6 studies, 213 participants; low-certainty evidence). Detection of lymph node tuberculosis For lymph node aspirates or biopsies, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 90.4% (95% CI 55.7% to 98.6%) (6 studies, 68 participants; very low-certainty evidence) and 89.8% (95% CI 71.5% to 96.8%) (6 studies, 142 participants; low-certainty evidence). Detection of rifampicin resistance Xpert MTB/RIF pooled sensitivity and specificity were 90.0% (67.6% to 97.5%) (6 studies, 20 participants; low-certainty evidence) and 98.3% (87.7% to 99.8%) (6 studies, 203 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: We found Xpert MTB/RIF sensitivity to vary by specimen type, with gastric aspirate specimens having the highest sensitivity followed by sputum and stool, and nasopharyngeal specimens the lowest; specificity in all specimens was > 98%. Compared with Xpert MTB/RIF, Xpert Ultra sensitivity in sputum was higher and specificity slightly lower. Xpert MTB/RIF was accurate for detection of rifampicin resistance. Xpert MTB/RIF was sensitive for diagnosing lymph node tuberculosis. For children with presumed tuberculous meningitis, treatment decisions should be based on the entirety of clinical information and treatment should not be withheld based solely on an Xpert MTB/RIF result. The small numbers of studies and participants, particularly for Xpert Ultra, limits our confidence in the precision of these estimates.


Assuntos
Tipagem Molecular/métodos , Tuberculose dos Linfonodos/diagnóstico , Tuberculose Meníngea/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Antibióticos Antituberculose/uso terapêutico , Viés , Criança , Fezes/microbiologia , Conteúdo Gastrointestinal/microbiologia , Humanos , Tipagem Molecular/normas , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose dos Linfonodos/tratamento farmacológico , Tuberculose dos Linfonodos/microbiologia , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Meníngea/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
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