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      The fecal, oral, and skin microbiota of children with Chagas disease treated with benznidazole

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          Abstract

          Background

          Chagas disease is still prevalent in rural areas of South America. In endemic areas of Bolivia, school children are screened for the program of Chagas disease eradication of the Ministry of Health, and positive children are treated. Here, we compared the fecal, oral and skin microbiomes of children with or without Chagas disease, and before and after benznidazol treatment of infected children.

          Methods

          A total of 543 Bolivian children (5–14 years old) were tested for Chagas disease, and 20 positive children were treated with Benznidazole. Fecal samples and oral and skin swabs were obtained before and after treatment, together with samples from a group of 35 uninfected controls. The 16S rRNA genes were sequenced and analyzed using QIIME to determine Alpha diversity differences and community distances, and linear discriminant analyses to determine marker taxa by infection status or treatment.

          Results

          Twenty out of 543 children screened were seropositive for Chagas disease (3.7%) and were included in the study, together with 35 control children that were seronegative for the disease. Fecal samples, oral and skin swabs were taken at the beginning of the study and after the anti-protozoa therapy with Benznidazole to the chagasic children. Infected children had higher fecal Firmicutes ( Streptococcus, Roseburia, Butyrivibrio, and Blautia), and lower Bacteroides and also showed some skin -but not oral- microbiota differences. Treatment eliminated the fecal microbiota differences from control children, increasing Dialister (class Clostridia) and members of the Enterobacteriaceae, and decreasing Prevotella and Coprococcus, with minor effects on the oral and skin bacterial diversity.

          Conclusions

          The results of this study show differences in the fecal microbiota associated with Chagas disease in children, and also evidence that treatment normalizes fecal microbiota (makes it more similar to that in controls), but is associated with oral and skin microbiota differences from control children. Since microbiota impacts in children, it is important to determine the effect of drugs on the children microbiota, since dysbiosis could lead to physiological effects which might be avoidable with microbiota restoration interventions.

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          Most cited references21

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          EMPeror: a tool for visualizing high-throughput microbial community data

          Background As microbial ecologists take advantage of high-throughput sequencing technologies to describe microbial communities across ever-increasing numbers of samples, new analysis tools are required to relate the distribution of microbes among larger numbers of communities, and to use increasingly rich and standards-compliant metadata to understand the biological factors driving these relationships. In particular, the Earth Microbiome Project drives these needs by profiling the genomic content of tens of thousands of samples across multiple environment types. Findings Features of EMPeror include: ability to visualize gradients and categorical data, visualize different principal coordinates axes, present the data in the form of parallel coordinates, show taxa as well as environmental samples, dynamically adjust the size and transparency of the spheres representing the communities on a per-category basis, dynamically scale the axes according to the fraction of variance each explains, show, hide or recolor points according to arbitrary metadata including that compliant with the MIxS family of standards developed by the Genomic Standards Consortium, display jackknifed-resampled data to assess statistical confidence in clustering, perform coordinate comparisons (useful for procrustes analysis plots), and greatly reduce loading times and overall memory footprint compared with existing approaches. Additionally, ease of sharing, given EMPeror’s small output file size, enables agile collaboration by allowing users to embed these visualizations via emails or web pages without the need for extra plugins. Conclusions Here we present EMPeror, an open source and web browser enabled tool with a versatile command line interface that allows researchers to perform rapid exploratory investigations of 3D visualizations of microbial community data, such as the widely used principal coordinates plots. EMPeror includes a rich set of controllers to modify features as a function of the metadata. By being specifically tailored to the requirements of microbial ecologists, EMPeror thus increases the speed with which insight can be gained from large microbiome datasets.
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            Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

            Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
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              The theory of disappearing microbiota and the epidemics of chronic diseases

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                Author and article information

                Contributors
                Role: InvestigationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Methodology
                Role: Data curationRole: Formal analysis
                Role: Formal analysisRole: Investigation
                Role: Data curationRole: Formal analysis
                Role: Data curationRole: Investigation
                Role: Data curationRole: Formal analysis
                Role: Data curationRole: Formal analysisRole: Investigation
                Role: ConceptualizationRole: Investigation
                Role: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 February 2019
                2019
                : 14
                : 2
                : e0212593
                Affiliations
                [1 ] Institut Pasteur de Montevideo, Montevideo, Uruguay
                [2 ] Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
                [3 ] Universidad Andina Simón Bolívar, Sucre, Bolivia
                [4 ] Division of Translational Medicine, New York University School of Medicine, New York, NY, United States of America
                [5 ] University San Francisco Javier de Chuquisaca, Sucre, Bolivia
                [6 ] Center for Integrative Biology, Universidad Mayor, Santiago de Chile, Chile
                [7 ] Genome Technology Center, New York University Langone Medical Center, New York, NY, United States of America
                Institute of Tropical Medicine (NEKKEN), Nagasaki University, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-6985-6171
                http://orcid.org/0000-0001-9372-8487
                http://orcid.org/0000-0003-3643-9632
                http://orcid.org/0000-0003-4451-126X
                http://orcid.org/0000-0002-6516-3404
                Article
                PONE-D-18-35488
                10.1371/journal.pone.0212593
                6391005
                30807605
                0d380adc-66c7-4d8a-a0b7-c500ff05e73a
                © 2019 Robello et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 May 2018
                : 14 December 2018
                Page count
                Figures: 4, Tables: 0, Pages: 11
                Funding
                Funded by: Emch Fund
                Award Recipient :
                Funded by: C&D Fund for Microbial Anthropology
                Award Recipient :
                We acknowledge the support of the C&D Fund for Microbial Anthropology, and the Emch Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbiome
                Biology and Life Sciences
                Genetics
                Genomics
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Microbiology
                Microbial Genomics
                Microbiome
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Chagas Disease
                Medicine and Health Sciences
                Parasitic Diseases
                Protozoan Infections
                Chagas Disease
                Medicine and Health Sciences
                Pediatrics
                Pediatric Infections
                Medicine and Health Sciences
                Dermatology
                Skin Infections
                Medicine and Health Sciences
                Infectious Diseases
                Skin Infections
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Streptococcal Infections
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Prevotella Infection
                Medicine and Health Sciences
                Parasitic Diseases
                Biology and Life Sciences
                Organisms
                Eukaryota
                Protozoans
                Parasitic Protozoans
                Trypanosoma
                Trypanosoma Cruzi
                Custom metadata
                Raw sequencing reads were uploaded to the public database Qiita (Study ID # 11724) and to the European Bioinformatics Institut (EBI) database under accession number ERP113722.

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                Uncategorized

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