Improved gut microbiome recovery following drug therapy is linked to abundance and replication of probiotic strains

Probiotics have been used for decades to alleviate the negative side-effects of oral antibiotics, but our mechanistic understanding on how they work is so far incomplete. Here, we performed a metagenomic analysis of the fecal microbiota in participants who underwent a 14-d Helicobacter pylori eradication therapy with or without consumption of a multi-strain probiotic intervention (L. paracasei CNCM I-1518, L. paracasei CNCM I-3689, L. rhamnosus CNCM I-3690, and four yogurt strains) in a randomized, double-blinded, controlled clinical trial. Using a strain-level analysis for detection and metagenomic determination of replication rate, ingested strains were detected and replicated transiently in fecal samples and in the gut during and following antibiotic administration. Consumption of the fermented milk product led to a significant, although modest, improvement in the recovery of microbiota composition. Stratification of participants into two groups based on the degree to which their microbiome recovered showed i) a higher fecal abundance of the probiotic L. paracasei and L. rhamnosus strains and ii) an elevated replication rate of one strain (L. paracasei CNCMI-1518) in the recovery group. Collectively, our findings show a small but measurable benefit of a fermented milk product on microbiome recovery after antibiotics, which was linked to the detection and replication of specific probiotic strains. Such functional insight can form the basis for the development of probiotic-based intervention aimed to protect gut microbiome from drug treatments

Chevilly, les Herbeauts et la Croix Rouge

Rapport de l'opération de fouille archéologique préventive de Chevilly, Les Herbeauts et La Croix Rouge (Loiret) 45 093 051 AH. Site A19 A1. Edité par l'INRAP Centre-Ile-de-France, Orléans en 2007. 303 p

System design using an inverse approach Application to the hybrid vehicle powertrain

VOL 40/3 - 2006 - pp. - doi:International audienceThe development of hybrid vehicles is nowadays a new challenge for the automotive industry since it appears a relevant solution to reach the next ten years pollution standards. The new advantages which could be achieved by hybrid architectures of powertrains are generally difficult to study. The purpose of this paper is to introduce a novel methodology based on an inverse approach that provide an help at the design and analysis stages of such type of systems. It allows to define in a first step the admissible architecture of the powertrain according to the objectives of the design, and in a second step to compare different solutions using the same references in a multi-objective context. The proposed approach is here detailed considering the study of the requirements for the powertrain architecture of a hybrid vehicle in order to achieve some consumption criteria on a standard road cycle

Design of a hybrid vehicle powertrain using an inverse methodology

International audienc

Mechatronic bond graph modelling of an automotive vehicle

Postprint version.International audienceAutomotive manufacturers have created vehicle models but these are somewhat complex and use black boxes with numerous tables and mappings. Each model is generally valid for its own field of use and can thus produce significant differences in results outside its specific. eld. Moreover vehicle behaviour requires detailing and analysis during precise manoeuvres called 'life situations'. These 'life situations' require different models to be set up. A complete vehicle model is necessary when attempting to reproduce simulated realistic behaviours for different manoeuvres. High modelling standards are also sought when vehicle systems such as steering, suspension or braking are approached. This paper presents bond graph modelling of an automotive vehicle with 16 degrees of freedom. Although not presented here, one purpose of such a model is dimensioning of different vehicle systems, in certain life situations, using an inverse approach. The vehicle body is modelled by a rigid body with six degrees of freedom. Each wheel has two degrees of freedom, one corresponding to vertical suspension deflection, the other to wheel axial rotation. Each front wheel has one additional degree of freedom corresponding to steering mobility. Vehicle components modelled and connected to the body model are thus four suspensions, wheels and steering system. Simulations of this model have been undertaken on 20Sim. They reveal good correlation with a model simulated on AMESim by automotive manufacturer PSA Peugeot Citroen, considered as the validation reference for this study

Positive Regulation of CXCR4 Expression and Signaling by Interleukin-7 in CD4(+) Mature Thymocytes Correlates with Their Capacity To Favor Human Immunodeficiency X4 Virus Replication

The emergence of X4 human immunodeficiency virus type 1 (HIV-1) variants in infected individuals is associated with poor prognosis. One of the possible causes of this emergence might be the selection of X4 variants in some specific tissue compartment. We demonstrate that the thymic microenvironment favors the replication of X4 variants by positively modulating the expression and signaling of CXCR4 in mature CD4(+) CD8(−) CD3(+) thymocytes. Here, we show that the interaction of thymic epithelial cells (TEC) with these thymocytes in culture induces an upregulation of CXCR4 expression. The cytokine secreted by TEC, interleukin-7 (IL-7), increases cell surface expression of CXCR4 and efficiently overcomes the downregulation induced by SDF-1α, also produced by TEC. IL-7 also potentiates CXCR4 signaling, leading to actin polymerization, a process necessary for virus entry. In contrast, in intermediate CD4(+) CD8(−) CD3(−) thymocytes, the other subpopulation known to allow virus replication, TEC or IL-7 has little or no effect on CXCR4 expression and signaling. CCR5 is expressed at similarly low levels in the two thymocyte subpopulations, and neither its expression nor its signaling was modified by the cytokines tested. This positive regulation of CXCR4 by IL-7 in mature CD4(+) thymocytes correlates with their high capacity to favor X4 virus replication compared with intermediate thymocytes or peripheral blood mononuclear cells. Indeed, we observed an enrichment of X4 viruses after replication in thymocytes initially infected with a mixture of X4 (NL4-3) and R5 (NLAD8) HIV strains and after the emergence of X4 variants from an R5 primary isolate during culture in mature thymocytes

Safety and functional enrichment of gut microbiome in healthy subjects consuming a multi-strain fermented milk product: a randomised controlled trial

International audienceAbstract Many clinical studies have evaluated the effect of probiotics, but only a few have assessed their dose effects on gut microbiota and host. We conducted a randomized, double-blind, controlled intervention clinical trial to assess the safety (primary endpoint) of and gut microbiota response (secondary endpoint) to the daily ingestion for 4 weeks of two doses (1 or 3 bottles/day) of a fermented milk product (Test) in 96 healthy adults. The Test product is a multi-strain fermented milk product, combining yogurt strains and probiotic candidate strains Lactobacillus paracasei subsp. paracasei CNCM I-1518 and CNCM I-3689 and Lactobacillus rhamnosus CNCM I-3690. We assessed the safety of the Test product on the following parameters: adverse events, vital signs, hematological and metabolic profile, hepatic, kidney or thyroid function, inflammatory markers, bowel habits and digestive symptoms. We explored the longitudinal gut microbiota response to product consumption and dose, by 16S rRNA gene sequencing and functional contribution by shotgun metagenomics. Safety results did not show any significant difference between the Test and Control products whatever the parameters assessed, at the two doses ingested daily over a 4-week-period. Probiotic candidate strains were detected only during consumption period, and at a significantly higher level for the three strains in subjects who consumed 3 products bottles/day. The global structure of the gut microbiota as assessed by alpha and beta-diversity, was not altered by consumption of the product for four weeks. A zero-inflated beta regression model with random effects (ZIBR) identified a few bacterial genera with differential responses to test product consumption dose compared to control. Shotgun metagenomics analysis revealed a functional contribution to the gut microbiome of probiotic candidates