Biology subjects

Blanchard, A.

Publications and source records attributed to Blanchard, A..

4 recordsLinked to original sources

bioRxiv2017

Metagenomic signature of natural strongyle infection in susceptible and resistant horses

Gastrointestinal strongyles are a major threat to horses' health and welfare. Given that strongyles inhabit the same niche as the gut microbiota, they may interact with each other. These beneficial or detrimental interactions are unknown in horses and could partly explain contrasted susceptibility to infection between individuals. To address these questions, an experimental pasture trial with 20 worm-free female Welsh ponies (10 susceptible (S) and 10 resistant (R) to parasite infection) was implemented for five months. Fecal egg counts (FEC), hematological and biochemical data, body weight and gut microbiota composition were studied in each individual after 0, 24, 43, 92 and 132 grazing days.\n\nThe predicted R ponies exhibited lower FEC after 92 and 132 grazing days, and showed higher levels of circulating monocytes and eosinophils, while S ponies developed lymphocytosis by the end of the trial. Although the overall microbiota diversity remained similar between the two groups, R and S ponies exhibited sustained differential abundances in Clostridium XIVa, Ruminococcus, Acetivibrio and unclassified Lachnospiracea at day 0. These bacteria may hence contribute to the intrinsic pony resistance towards strongyle infection. Moreover, Paludibacter, Campylobacter, Bacillus, Pseudomonas, Clostridium III, Acetivibrio, members of the unclassified Eubacteriaceae and Ruminococcaceae and fungi loads were increased in infected S ponies, suggesting that strongyle and fungi may contribute to each others success in the ecological niche of the equine intestines. In contrast, butyrate-producing bacteria such as Ruminococcus, Clostridium XIVa and members of the Lachnospiraceae family decreased in S relative to R ponies. Additionally, these gut microbiota alterations induced changes in several immunological pathways in S ponies, including pathogen sensing, lipid metabolism, and activation of signal transduction that are critical for the regulation of immune system and energy homeostasis. These observations shed light on a putative implication of the gut microbiota in the intrinsic resistance to strongyle infection.\n\nOverall, this longitudinal study provides a foundation to better understand the mechanisms that underpin the relationship between host susceptibility to strongyle infection, immune response and gut microbiota under natural conditions in horses and should contribute to the development of novel biomarkers of strongyle susceptibility and provide additional control options.

systems biology↗

bioRxiv2017

Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A

Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. Whole exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A), as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss of function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.

genetics↗

bioRxiv2017

DirtyGenes: significance testing for gene or bacterial population composition changes using the Dirichlet distribution

High throughput sequencing, and quantitative polymerase chain reaction (qPCR), can detect changes in bacterial communities or the genes that they carry, between different environments or treatments. These methods are applied widely to microbiomes in humans, animals, soil and water; an important application is for changes in antimicrobial resistance genes (ARGs). However, at present, there is no statistical method to determine whether observed changes in the overall composition are significant, or result from random variations between samples. Therefore researchers are limited to graphical descriptions. We describe a novel statistical method to determine whether or not observed differences in bacterial populations or their genes are significant. It can be used with data from shotgun metagenomics, 16S characterisation or qPCR. It can also be used for experimental design, to calculate the number of samples needed in future experiments. We show its application to two example data sets. The first is published data on bacterial communities and ARGs in the environment, in which we show that there are significant changes in both ARG and community composition. The second is a new data set on seasonality in bacterial communities and ARGs in hooves from four sheep. While the observed differences are not significant, we show that a minimum group size of eight sheep in a future experiment would provide sufficient power to observe significant changes, should the already observed changes be true. This method has broad uses for statistical testing and experimental design in experiments on changing microbiomes, including for studies on antimicrobial resistance.

bioinformatics↗

bioRxiv2017

Risk factor analysis of equine strongyle resistance to anthelmintics

Intestinal strongyles are the most problematic endoparasites of equids as a result of their wide distribution and the spread of resistant isolates throughout the world. While abundant literature can be found on the extent of anthelmintic resistance across continents, empirical knowledge about associated risk factors is missing. This study brought together results from anthelmintic efficacy testing and risk factor analysis to provide evidence-based guidelines in the field. It involved 688 horses from 39 French horse farms and riding schools to both estimate Faecal Egg Count Reduction (FECR) after anthelmintic treatment and to interview farm and riding school managers about their practices. Risk factors associated with reduced anthelmintic efficacy in equine strongyles were estimated across drugs using a marginal modelling approach. Results demonstrated ivermectin efficacy (96.3% FECR), the inefficacy of fenbendazole (42.8% FECR) and an intermediate profile for pyrantel (90.3% FECR). Risk factor analysis provided support to advocate for FEC-based treatment regimens combined with individual anthelmintic dosage and the enforcement of tighter biosecurity around horse introduction that contributed to lower drug resistance risk by 1.75. Premises falling under this typology also relied more on their veterinarians suggesting they play an important role in the sustainability of anthelmintic usage. Similarly, drug resistance risk was halved in premises with frequent pasture rotation and with stocking rate below five horses/ha. This is the first empirical risk factor analysis for anthelmintic resistance in equids, whose findings should guide the implementation of more sustained strongyle management in the field.

zoology↗