Biology subjects

Ghozlane, A.

Publications and source records attributed to Ghozlane, A..

5 recordsLinked to original sources

bioRxiv2019

SHAMAN: a user-friendly website for metataxonomic analysis from raw reads to statistical analysis

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 representation of the detected signatures. Such an analysis is normally obtained by using a set of different applications that require specific expertise for installation, data processing and in some case, programming skills. 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 among the largest panels of interactive visualizations as compared to the other options that are currently available. SHAMAN is specifically designed for non-expert users who may benefit from using 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 datasets (a mock community sequencing and published 16S metagenomic data), we illustrate the strengths of SHAMAN in quickly performing a complete metataxonomic analysis.

bioinformatics↗

bioRxiv2018

A role for gut microbiota in m6A epitranscriptomic mRNA modifications in different host tissues

The intestinal microbiota modulates host physiology and gene expression via mechanisms that are not fully understood. A recently discovered layer of gene expression regulation is N6-methyladenosine (m6A) modification of mRNA. To unveil if this epitranscriptomic mark in part mediates the impact of the gut microbiota on the host, we analyzed m6A-modifications in transcripts of mice displaying either a conventional, or a modified, or no gut flora. We discovered that the microbiota has a strong influence on m6A-modifications in the cecum, and also, albeit to a lesser extent, in the liver. We furthermore show that a single commensal bacterium, Akkermansia muciniphila, can affect specific m6A modifications. Together, we report here epitranscriptomic modifications as an unexpected level of interaction in the complex interplay between commensal bacteria and their host.

molecular biology↗

bioRxiv2017

Diverse laboratory colonies of Aedes aegypti harbor the same adult midgut bacterial microbiome

BackgroundHost-associated microbes, collectively known as the microbiota, play an important role in the biology of multicellular organisms. In mosquito vectors of human pathogens, the gut bacterial microbiota influences vectorial capacity and has become the subject of intense study. In laboratory studies of vector biology, genetic effects are often inferred from differences between geographically and genetically diverse colonies of mosquitoes that are reared in the same insectary. It is unclear, however, to what extent genetic effects can be confounded by uncontrolled differences in the microbiota composition among mosquito colonies. To address this question, we used 16S metagenomics to compare the midgut bacterial microbiome of six recent laboratory colonies of Aedes aegypti representing the geographical range and genetic diversity of the species.\n\nResultsWe found that the diversity, abundance, and community structure of the midgut bacterial microbiome was remarkably similar among the six different colonies of Ae. aegypti, regardless of their geographic origin. We also confirmed the relatively low complexity of bacterial communities inhabiting the mosquito midgut.\n\nConclusionsOur finding that geographically diverse colonies of Ae. aegypti reared in the same insectary harbor a similar gut bacterial microbiome supports the conclusion that the gut microbiota of adult mosquitoes is environmentally determined regardless of the host genotype. Thus, uncontrolled differences in microbiota composition are unlikely to represent a significant confounding factor in genetic studies of vector biology.

genetics↗

bioRxiv2017

Prediction of the intestinal resistome by a novel 3D-based method

The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens. Yet, this question remains hypothetical because of the difficulty to identify ARDs from intestinal bacteria. Here, we developed and validated a new annotation method (called pairwise comparative modelling, PCM) based on homology modelling in order to characterize the Human resistome. We were able to predict 6,095 ARDs in a 3.9 million protein catalogue from the Human intestinal microbiota. We found that predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino-acid identity 29.8%). Among 3,651 pdARDs that were identified in metagenomic species, 3,489 (95.6%) were assumed to be located on the bacterial chromosome. Furthermore, genes associated with mobility were found in the neighbourhood of only 7.9% (482/6,095) of pdARDs. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n=663) into 6 \"resistotypes\". Eventually, we found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics. Altogether, our results support that most ARDs in the intestinal microbiota should be considered as intrinsic genes of commensal microbiota with a low risk of transfer to bacterial pathogens.

microbiology↗

bioRxiv2017

Protection of the human gut microbiome from antibiotics

BackgroundAntibiotics are life-saving drugs but severely affect the gut microbiome with short term consequences including diarrhoea, Clostridium difficile infections and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.\n\nMethodsWe performed a randomized controlled trial (ClinicalTrials.gov NCT02176005) in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in two parallel groups, with or without DAV132 co-administration. Two control goups of 8 volunteers each receiving DAV132 alone, or a non-active substitute, were added.\n\nResultsThe co-administration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex-vivo.\n\nConclusionsDAV132 was highly effective to protect the gut microbiome of moxifloxacin - treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.

clinical trials↗