The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation

We thank Manuel Kulagin for technical help, Pierre Bonnaventure for portal vein blood sampling, Francisco Sepulveda for technical assistance in GS-MS acquisition, and Dorothee Hahne (Metabolomics Australia, University of Western Australia) for human samples SCFA isolation, acquisition, and analysis. We also thank Cristina Cartoni (Phenotyping Unit, EPFL) for Milliplex analysis, Jessica Dessimoz and her team from the Histology Core Facility (EPFL), Miguel Garcia and his team from the Flow Cytometry Core Facility (EPFL), and staff from the EPFL CPG animal house for excellent animal care. The computations were partially performed at the Vital-IT Center for high-performance computing of the SIB Swiss Institute of Bioinformatics (http://www.vital-it.ch). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 310948. Funding for A.W.W. and a subset of the 16S rRNA gene sequencing was provided by the Wellcome Trust (grant number WT 098051). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Genetic and dietary modulators of the inflammatory response in the gastrointestinal tract of the BXD mouse genetic reference population.

peer reviewedInflammatory gut disorders, including inflammatory bowel disease (IBD), can be impacted by dietary, environmental, and genetic factors. While the incidence of IBD is increasing worldwide, we still lack a complete understanding of the gene-by-environment interactions underlying inflammation and IBD. Here, we profiled the colon transcriptome of 52 BXD mouse strains fed with a chow or high-fat diet (HFD) and identified a subset of BXD strains that exhibit an IBD-like transcriptome signature on HFD, indicating that an interplay of genetics and diet can significantly affect intestinal inflammation. Using gene co-expression analyses, we identified modules that are enriched for IBD-dysregulated genes and found that these IBD-related modules share cis-regulatory elements that are responsive to the STAT2, SMAD3, and REL transcription factors. We used module quantitative trait locus analyses to identify genetic loci associated with the expression of these modules. Through a prioritization scheme involving systems genetics in the mouse and integration with external human datasets, we identified Muc4 and Epha6 as the top candidates mediating differences in HFD-driven intestinal inflammation. This work provides insights into the contribution of genetics and diet to IBD risk and identifies two candidate genes, MUC4 and EPHA6, that may mediate IBD susceptibility in humans

The skin microbiome in the first year of life and its association with atopic dermatitis

publishedVersio

Intestinal helminths modulate the gut microbiome

Intestinal parasitic worms (commonly named intestinal helminths) affect close to one quarter of the world population and cause major losses for the livestock industry. These parasites establish chronic infections by modulation the immunity of their host. The immune system of mammals has been challenged by this immuno-modulation all along the course of evolution. Although intestinal parasites constitute a threat to human health, their recent eradication from industrialized regions may not be without consequence. In fact, the loss of intestinal helminth-driven immuno-regulation has been proposed to underlie the increased frequency of immune disorders observed in developed areas. Here, we first showed that one immune-modulatory strategy of intestinal helminths involves alterations of the intestinal bacterial communities. Although a lot remained to be understood about these alterations, they were characterized by higher intestinal levels of short-chain fatty acids (SCFAs), bacterial metabolites with immuno-suppressive activity. A better understanding of how intestinal helminths modulate host immunity via the intestinal microbiome may open the door to novel strategies to fight both intestinal parasites and immune disorders. In this context, I further characterized the impact of intestinal helminths on fecal bacterial communities in children living in a rural region of Ecuador and naturally infected with Ascaris lumbricoides, a parasite affecting 1.2 billion people worldwide. I then used a mouse model to extensively characterize the impact of intestinal helminth infection on intestinal bacterial communities along the intestinal tract. Based on our main results, we hypothesized that the worm-induced mucus secretion may favor the growth of SCFA-producing bacteria in the intestine, which in turn down-regulates the host immunity by promoting regulatory T cells. As part of this work, I also developed a web-based platform to assist scientists in analyzing data from high-throughput nucleic-acid sequencing, a method commonly used to characterize microbial communities but for which data analysis remains particularly challenging

Impulsivité en psychiatrie (définitions, mécanismes, prise en charge et perspectives)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Data integration in systems genetics and aging research

Human life expectancy has dramatically improved over the course of the last century. Although this reflects a global improvement in sanitation and medical care, this also implies that more people suffer from diseases that typically manifest later in life, like Alzheimer and atherosclerosis. Increasing healthspan by delaying or reverting the development of these age-related diseases has therefore become an urgent challenge in biomedical research. Research in this field is complicated by the multi-factorial nature of age-related diseases. They are rooted in complex physiological mechanisms impacted by heritable, environment and life-style factors that can be unique to each individual. Although technological advances in high-throughput biomolecular assays have enabled researchers to investigate individual physiology at the molecular level, integrating information about its different components, and accounting for individual variations remains a challenge. We are using a large collection of omics and phenotype data derived from the BXD mouse genetic diversity panel to explore how good data management practices, as fostered by the FAIR principles, paired with an explainable artificial intelligence framework, can provide solutions to decipher the complex roots of age-related diseases. These developments will help to propose innovative approaches to extend healthspan in the aging global population.Comment: 7 pages, 3 figures, Proceedings of the Swiss Research Data Day 2020, Oct. 22 2020. For full conference proceedings see http://www.ressi.ch/sites/default/files/No_special_DLCM.pd

Distribution spatiale et mobilité du phosphore sédimentaire dans une retenue hydroélectrique

International audienceMalgré la réduction des rejets de phosphore (P) dans l’environnement, les efflorescences phytoplanctoniques sont toujours observées dans un grand nombre de masses d’eau. C’est notamment le cas dans les retenues de barrage où la perturbation de la continuité sédimentaire peut conduireà une accumulation importante de phosphore au sein du compartiment sédimentaire. Ainsi, pour lutter contre l’eutrophisation, une meilleure connaissance de la distribution, de la réactivité et de la mobilité du P sédimentaire s’avère indispensable. Dans ce contexte, les sédiments de surface de la retenue de Champsanglard (Creuse, France) ont été prélevés en différents points selon un gradient amont/aval. Une caractérisation physico-chimique (granulométrie; teneurs en P, Fe, Al, matière organique; fractionnement chimique du P suivant le protocole de RYDIN et WELCH [1998]) a été effectuée afin d’évaluer le potentiel de relargage de P de ces sédiments. Les résultats montrent une évolution de la concentration et de la distribution du P dans les sédiments de surface dans la retenue de l’amont vers l’aval (de 1,5 à 2,3 mg P∙gsec -1), qui semble corrélée avec l’évolution de la granulométrie. L’analyse du fractionnement chimique a montré que le P était majoritairement lié aux oxyhydroxydes de Fe et Mn amorphes (66 %), ces concentrations augmentant également à l’approche du barrage. Ces résultats indiquent que les conditions d’oxydoréduction sont l’un des paramètres clés du contrôle de la remobilisation du P sédimentaire vers la colonne d’eau. À l’opposé, le P associé aux fractions de lamatière organique et de l’aluminium ne semble quant à lui ne pas évoluer spatialement de façon significative

Distribution spatiale et mobilité du phosphore sédimentaire dans une retenue hydroélectrique

International audienceMalgré la réduction des rejets de phosphore (P) dans l’environnement, les efflorescences phytoplanctoniques sont toujours observées dans un grand nombre de masses d’eau. C’est notamment le cas dans les retenues de barrage où la perturbation de la continuité sédimentaire peut conduireà une accumulation importante de phosphore au sein du compartiment sédimentaire. Ainsi, pour lutter contre l’eutrophisation, une meilleure connaissance de la distribution, de la réactivité et de la mobilité du P sédimentaire s’avère indispensable. Dans ce contexte, les sédiments de surface de la retenue de Champsanglard (Creuse, France) ont été prélevés en différents points selon un gradient amont/aval. Une caractérisation physico-chimique (granulométrie; teneurs en P, Fe, Al, matière organique; fractionnement chimique du P suivant le protocole de RYDIN et WELCH [1998]) a été effectuée afin d’évaluer le potentiel de relargage de P de ces sédiments. Les résultats montrent une évolution de la concentration et de la distribution du P dans les sédiments de surface dans la retenue de l’amont vers l’aval (de 1,5 à 2,3 mg P∙gsec -1), qui semble corrélée avec l’évolution de la granulométrie. L’analyse du fractionnement chimique a montré que le P était majoritairement lié aux oxyhydroxydes de Fe et Mn amorphes (66 %), ces concentrations augmentant également à l’approche du barrage. Ces résultats indiquent que les conditions d’oxydoréduction sont l’un des paramètres clés du contrôle de la remobilisation du P sédimentaire vers la colonne d’eau. À l’opposé, le P associé aux fractions de lamatière organique et de l’aluminium ne semble quant à lui ne pas évoluer spatialement de façon significative

Infection with a small intestinal helminth, Heligmosomoides polygyrus bakeri, consistently alters microbial communities throughout the murine small and large intestine

Increasing evidence suggests that intestinal helminth infection can alter intestinal microbial communities with important impacts on the mammalian host. However, all of the studies to date utilize different techniques to study the microbiome and access different sites of the intestine with little consistency noted between studies. In the present study, we set out to perform a comprehensive analysis of the impact of intestinal helminth infection on the mammalian intestinal bacterial microbiome. For this purpose, we investigated the impact of experimental infection using the natural murine small intestinal helminth, Heligmosomoides polygyrus bakeri and examined possible alterations in both the mucous and luminal bacterial communities along the entire small and large intestine. We also explored the impact of common experimental variables including the parasite batch and pre-infection microbiome, on the outcome of helminth-bacterial interactions. This work provides evidence that helminth infection reproducibly alters intestinal microbial communities, with an impact of infection noted along the entire length of the intestine. Although the exact nature of helminth-induced alterations to the intestinal microbiome differed depending on the microbiome community structure present prior to infection, changes extended well beyond the introduction of new bacterial species by the infecting larvae. Moreover, striking similarities between different experiments were noted, including the consistent outgrowth of a bacterium belonging to the Peptostreptococcaceae family throughout the intestine. (C) 2019 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved

Diagenetic formation of stevensite by replacement of diatom frustules in the sediments of the alkaline Lake Alchichica (Mexico)

Better understanding the conditions of formation of authigenic Mg-silicates and their reactivity is key to interpret the palaeoenvironmental message carried by the sedimentary record and evaluate the effect of reverse weathering, a process involved in long-term climate evolution. Microbialites from most alkaline crater lakes in Mexico contain Mg-silicates except those in Lake Alchichica, where concentration of orthosilicic acid is low (m). This study investigated the first metre of sediments in Lake Alchichica in order to check how their mineralogy compared with that of shoreline microbialites. The mineralogy and chemistry of the sediment column were determined, together with the pore water chemistry, providing insights on the processes occurring during early diagenesis. Below ca 3 cm in depth, diatom frustules are progressively pseudomorphized into Al-poor Mg-silicates with a composition corresponding to stevensite. This diagenetic process is massive and the resulting silicate represents between 30 and 53 wt.% of the sediment content at all depths. This observation questions the possibility to infer lake palaeochemistry from the presence/absence of Mg-silicates in the sedimentary record. Moreover, it allowed refinement of the conditions under which Mg-silicates authigenesis occurs: the saturation of the solution should be higher or equal to the solubility of a Mg-silicate phase close to that of 'amorphous sepiolite'. Although the solubility of authigenic silicates is a key parameter of reverse weathering modelling during geological times, it is still debated. In this study, a solubility constant deduced from a natural system is proposed that should be considered when modelling the formation of Mg-silicates in a natural environment. The proportion of reverse weathering associated with this solubility constant could be higher than previously predicted based on experiments and thus have a greater impact on climate stability over geological timescales