Project description: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. Using a mouse model mimicking pediatric antibiotic use, we found that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide altered both host and microbiota development. Early-life PAT accelerated total mass and bone growth, and resulted in progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. While control microbiota rapidly adapted to a change in diet, PAT slowed the ecological progression, with delays lasting several months in response to the macrolide. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment. C57BL/6J mice received three antibiotic courses: at days 10-15, 28-31, and 37-40 of life, amoxicillin or tylosin.Livers were collected at age 22 weeks, RNA was extracted, and transcriptional differences were measured by microarray analysis.
Project description: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. Using a mouse model mimicking pediatric antibiotic use, we found that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide altered both host and microbiota development. Early-life PAT accelerated total mass and bone growth, and resulted in progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. While control microbiota rapidly adapted to a change in diet, PAT slowed the ecological progression, with delays lasting several months in response to the macrolide. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
Project description:Next-Generation-Sequencing (NGS) technologies have led to important improvement in the detection of new or unrecognized infective agents, related to infectious diseases. In this context, NGS high-throughput technology can be used to achieve a comprehensive and unbiased sequencing of the nucleic acids present in a clinical sample (i.e. tissues). Metagenomic shotgun sequencing has emerged as powerful high-throughput approaches to analyze and survey microbial composition in the field of infectious diseases. By directly sequencing millions of nucleic acid molecules in a sample and matching the sequences to those available in databases, pathogens of an infectious disease can be inferred. Despite the large amount of metagenomic shotgun data produced, there is a lack of a comprehensive and easy-use pipeline for data analysis that avoid annoying and complicated bioinformatics steps. Here we present HOME-BIO, a modular and exhaustive pipeline for analysis of biological entity estimation, specific designed for shotgun sequenced clinical samples. HOME-BIO analysis provides comprehensive taxonomy classification by querying different source database and carry out main steps in metagenomic investigation. HOME-BIO is a powerful tool in the hand of biologist without computational experience, which are focused on metagenomic analysis. Its easy-to-use intrinsic characteristic allows users to simply import raw sequenced reads file and obtain taxonomy profile of their samples.
Project description:Next-Generation-Sequencing (NGS) technologies have led to important improvement in the detection of new or unrecognized infective agents, related to infectious diseases. In this context, NGS high-throughput technology can be used to achieve a comprehensive and unbiased sequencing of the nucleic acids present in a clinical sample (i.e. tissues). Metagenomic shotgun sequencing has emerged as powerful high-throughput approaches to analyze and survey microbial composition in the field of infectious diseases. By directly sequencing millions of nucleic acid molecules in a sample and matching the sequences to those available in databases, pathogens of an infectious disease can be inferred. Despite the large amount of metagenomic shotgun data produced, there is a lack of a comprehensive and easy-use pipeline for data analysis that avoid annoying and complicated bioinformatics steps. Here we present HOME-BIO, a modular and exhaustive pipeline for analysis of biological entity estimation, specific designed for shotgun sequenced clinical samples. HOME-BIO analysis provides comprehensive taxonomy classification by querying different source database and carry out main steps in metagenomic investigation. HOME-BIO is a powerful tool in the hand of biologist without computational experience, which are focused on metagenomic analysis. Its easy-to-use intrinsic characteristic allows users to simply import raw sequenced reads file and obtain taxonomy profile of their samples.
Project description:We used a metagenomic microarray to detect Human Pegivirus in serum and cerebrospinal fluid from a patient suffering from severe encephalitis.
Project description:Characterization of a metagenomic regulatory sequence library derived from M. xanthus, E. coli, and O. urethralis genomes in strains expressing different RpoD ortholog variants. Targeted DNA and RNA seq used to profile relative DNA and RNA abundances, respectively of each regulatory sequence construct in the library.
Project description:Hospitalized preterm infants receive frequent and often prolonged exposures to antibiotics because they are vulnerable to infection. It is not known whether the short-term effects of antibiotics on the preterm infant gut microbiota and resistome persist after discharge from neonatal intensive care units. Here, we use complementary metagenomic, culture-based and machine learning techniques to study the gut microbiota and resistome of antibiotic-exposed preterm infants during and after hospitalization, and we compare these readouts to antibiotic-naive healthy infants sampled synchronously. We find a persistently enriched gastrointestinal antibiotic resistome, prolonged carriage of multidrug-resistant Enterobacteriaceae and distinct antibiotic-driven patterns of microbiota and resistome assembly in extremely preterm infants that received early-life antibiotics. The collateral damage of early-life antibiotic treatment and hospitalization in preterm infants is long lasting. We urge the development of strategies to reduce these consequences in highly vulnerable neonatal populations.