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[hal-02637857] Phylogenetic network analysis applied to pig gut microbiota identifies an ecosystem structure linked with growth traits
The ecological interactions within the gut microbial communities are complex and far from being fully understood. Here we report the first study that aims at defining the interaction network of the gut microbiota in pigs and comparing it with the enterotype-like clustering analysis. Fecal microbiota of 518 healthy piglets was characterized by 16S ribosomal RNA gene sequencing. Two networks were constructed at the genus and operational taxonomic unit levels. Within-network interactions mirrored the human gut microbiota relationships, with a strong co-exclusion between Prevotella and Ruminococcus genera, and were consistent with the two enterotype-like clusters identified in the pig microbiota. Remarkably, the cluster classification of the individuals was significantly associated with the body weight at 60 days of age (P=0.005) and average daily gain (P=0.027). To the best of our knowledge, this is the first study to provide an integrated overview of the porcine gut microbiota that suggests a conservation of the ecological community interactions and functional architecture between humans and pig. Moreover, we show that the microbial ecosystems and porcine growth traits are linked, which allows us to foresee that the enterotype concept may have an important role in the animal production industry.The ISME Journal advance online publication, 13 May 2016; doi:10.1038/ismej.2016.77.
ano.nymous@ccsd.cnrs.fr.invalid (Yuliaxis Ramayo-Caldas) 15 Mar 2024
https://hal.inrae.fr/hal-02637857v1
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[hal-01194002] Gut microbiota in swine: composition, genetic parameters, and links with immunity and production traits
absent
ano.nymous@ccsd.cnrs.fr.invalid (Jordi Estellé) 04 Sep 2015
https://hal.science/hal-01194002v1
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[hal-02742708] Microbiote intestinal chez le porc : paramètres génétiques de sa composition et liens avec des caractères immunitaires
L’objectif de cette étude est d’estimer les paramètres génétiques de la composition du microbiote intestinal chez le porc Large White et d’étudier les covariations entre cette composition et des paramètres immunitaires et de croissance. Dans le cadre du projet Sus-Flora, nous avons caractérisé la diversité du microbiote fécal pour 518 porcelets âgés de 60 jours, par séquençage d’une région variable du gène bactérien codant l’ARNr 16S. Nos premiers résultats ont mis en évidence une prédominance des genres bactériens Prevotella puis Oscillibacter, Dialister, Roseburia et Treponema. Des valeurs d’héritabilité comprises entre 0,13 0,08 et 0,55 0,16 ont été estimées pour l’abondance relative de 19 genres bactériens parmi les plus fréquents, démontrant ainsi une part génétique significative de la composition du microbiote intestinal chez le porc. Des corrélations génétiques positives et négatives sont identifiées entre abondances des taxons bactériens. Des covariations positives et négatives ont été trouvées entre des paramètres de formule sanguine (taux de monocytes, éosinophiles, plaquettes) et l’abondance des genres Prevotella, Roseburia, Dialister. Nous montrons également, pour un sous-groupe de 31 animaux, que la composition du microbiote intestinal se stabilise après 36 jours d’âge et que les animaux se séparent en deux groupes sur la base de la composition de leur microbiote intestinal, évoquant les entérotypes identifiés chez l’homme. Ces deux groupes, dominés par le genre Prevotella ou les Ruminococcaceae, sont retrouvés à 60 jours d’âge, avec la cohorte des 518 porcelets.
ano.nymous@ccsd.cnrs.fr.invalid (Jordi Estellé) 03 Jun 2020
https://hal.inrae.fr/hal-02742708v1
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[hal-02737197] Immunome differences between porcine ileal and jejunal Peyer’s patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues
[...]
ano.nymous@ccsd.cnrs.fr.invalid (Tatiana Maroilley) 02 Jun 2020
https://hal.inrae.fr/hal-02737197v1
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[hal-01193881] Extensive comparison of genome wide transcription along pig small intestine and in Peyer’s patces by RNA-seq
absent
ano.nymous@ccsd.cnrs.fr.invalid (Núria Mach) 04 Sep 2015
https://hal.science/hal-01193881v1
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[hal-02288150] Microbiote intestinal chez le porc : paramètres génétiques de sa composition et liens avec des caractères immunitaires
Microbiote intestinal chez le porc : paramètres génétiques de sa composition et liens avec des caractères immunitaires. 48. Journées de la Recherche Porcine
ano.nymous@ccsd.cnrs.fr.invalid (Jordi Estellé) 03 Jun 2020
https://hal.science/hal-02288150v1
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[hal-01193806] Extensive expression differences along porcine small intestine evidenced by transcriptome sequencing
The aim of this study was to analyse gene expression along the small intestine (duodenum, jejunum, ileum) and in the ileal Peyer's patches in four young pigs with no clinical signs of disease by transcriptome sequencing. Multidimensional scaling evidenced that samples clustered by tissue type rather than by individual, thus prefiguring a relevant scenario to draw tissue-specific gene expression profiles. Accordingly, 1,349 genes were found differentially expressed between duodenum and jejunum, and up to 3,455 genes between duodenum and ileum. Additionally, a considerable number of differentially expressed genes were found by comparing duodenum (7,027 genes), jejunum (6,122 genes), and ileum (6,991 genes) with ileal Peyer's patches tissue. Functional analyses revealed that most of the significant differentially expressed genes along small intestinal tissues were involved in the regulation of general biological processes such as cell development, signalling, growth and proliferation, death and survival or cell function and maintenance. These results suggest that the intrinsic large turnover of intestinal tissues would have local specificities at duodenum, ileum and jejunum. In addition, in concordance with their biological function, enteric innate immune pathways were overrepresented in ileal Peyer's patches. The reported data provide an expression map of the cell pathway variation in the different small intestinal tissues. Furthermore, expression levels measured in healthy individuals could help to understand changes in gene expression that occur in dysbiosis or pathological states.
ano.nymous@ccsd.cnrs.fr.invalid (Núria Mach) 28 May 2020
https://hal.science/hal-01193806v1
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[hal-02356215] Immunome differences between porcine ileal and jejunal Peyer’s patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues
The epithelium of the intestinal mucosa and the gut-associated lymphoid tissues (GALT) constitute an essential physical and immunological barrier against pathogens. In order to study the specificities of the GALT transcriptome in pigs, we compared the transcriptome profiles of jejunal and ileal Peyer's patches (PPs), mesenteric lymph nodes (MLNs) and peripheral blood (PB) of four male piglets by RNA-Seq. We identified 1,103 differentially expressed (DE) genes between ileal PPs (IPPs) and jejunal PPs (JPPs), and six times more DE genes between PPs and MLNs. The master regulator genes FOXP3, GATA3, STAT4, TBX21 and RORC were less expressed in IPPs compared to JPPs, whereas the transcription factor BCL6 was found more expressed in IPPs. In comparison between IPPs and JPPs, our analyses revealed predominant differential expression related to the differentiation of T cells into Th1, Th2, Th17 and iTreg in JPPs. Our results were consistent with previous reports regarding a higher T/B cells ratio in JPPs compared to IPPs. We found antisense transcription for respectively 24%, 22% and 14% of the transcripts detected in MLNs, PPs and PB, and significant positive correlations between PB and GALT transcriptomes. Allele-specific expression analyses revealed both shared and tissue-specific cis-genetic control of gene expression.
ano.nymous@ccsd.cnrs.fr.invalid (T. Maroilley) 26 May 2020
https://hal.science/hal-02356215v1
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[hal-01193953] Gut microbiota composition in swine: genetic parameters and links with immunity traits
absent
ano.nymous@ccsd.cnrs.fr.invalid (Jordi Estellé) 03 Jun 2020
https://hal.science/hal-01193953v1
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[hal-01193883] Exhaustive comparison of gene expression along pig small Intestine and in Peyer’s patches performed by RNA-Seq
absent
ano.nymous@ccsd.cnrs.fr.invalid (Núria Mach) 04 Sep 2015
https://hal.science/hal-01193883v1
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[hal-02733939] On the influence of host genetics on gut microbiota composition in pigs
[...]
ano.nymous@ccsd.cnrs.fr.invalid (Jordi Estellé) 02 Jun 2020
https://hal.inrae.fr/hal-02733939v1
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[hal-00083970] SUT1-promoted sterol uptake involves the ABC transporter Aus1 and the mannoprotein Dan 1 whose synergistic action is sufficient for this process
Efficient sterol influx in the yeast Saccharomyces cerevisiae is restricted to anaerobiosis or to haem deficiency resulting from mutations. Constitutive expression of SUT1, an hypoxic gene encoding a transcriptional regulator, induces sterol uptake in aerobiosis. Agenome-wide approach singDNAmicroarraywas used to identify the mediators of SUT1 effects on aerobic sterol uptake. A total of 121 ORFs (open reading frames) were significantly and differentially expressed after SUT1 verexpression, 61 downregulated and 60 up-regulated. Among these genes, the role of the putative ABC transporter (ATP-binding-cassette transporter) Aus1, and of the cell-wall mannoprotein Dan1, was characterized better. These two genes play an essential role in aerobic sterol uptake, since their deletion compromised the SUT1 effects, but individual overexpression of either of these genes in a wild-type background was not sufficient for this process. However, constitutive co-expression of AUS1 and DAN1 in a wild-type background resulted in sterol influx in aerobiosis. These results suggest that the corresponding proteins may act synergistically in vivo to promote sterol uptake.
ano.nymous@ccsd.cnrs.fr.invalid (Parissa Alimardani) 05 Jul 2006
https://hal.science/hal-00083970v1
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[anses-03658970] Increasing incidence of Enterococcus-associated diseases in poultry in France over the past 15 years
Enterococci are commensal intestinal bacteria and opportunistic pathogens in humans and animals. Enterococcus-associated diseases are an emerging health issue in poultry. The aim of this retrospective study was to assess the occurrence of enterococci in poultry in France with regard to the manifested diseases and the affected avian species. Our analysis is based on veterinary laboratory data collected by the French poultry epidemiological surveillance network (RNOEA) that monitors avian diseases in France based on the voluntary participation of its veterinarian members. Since the creation of the network in 1989, 12, 177 Enterococcus cases have been reported by veterinary laboratories (Enterococcus cecorum 53.1% and Enterococcus faecalis 24.3%), with emergence starting in 2006, year in which Enterococcus represented 0.4% of all reported pathogens, and incidence growing to 12.9% in 2020. The main diseases associated with these reports were locomotor disorders 35.2% (mainly involving E. cecorum 77.9%), septicaemia 34.9% (involving E. cecorum 53.4% and E. faecalis 23.8%), and omphalitis 14.4% (mainly involving E. faecalis 59.5%). Most of these Enterococcus-associated diseases (71.5%) were reported in broilers (particularly affected by the locomotor disorders and septicaemia involving E. cecorum), accounting for 9.1% of all the diseases reported in this production sector, with an increase from 1.4% in 2006 to 17.2% in 2020. This study highlights the emergence of enterococcal diseases in poultry in France over the past 15 years and the need to maintain a surveillance system.
ano.nymous@ccsd.cnrs.fr.invalid (Rozenn Souillard) 22 Jul 2024
https://anses.hal.science/anses-03658970v1
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[hal-02941029] Sulfiredoxin Protects Mice from Lipopolysaccharide-Induced Endotoxic Shock
Peroxiredoxins constitute a major family of cysteine-based peroxide-scavenging enzymes. They carry an intriguing redox switch by undergoing substrate-mediated inactivation via overoxidation of their catalytic cysteine to the sulfinic acid form that is reverted by reduction catalyzed by the sulfinic acid reductase sulfiredoxin (Srx). The biological significance of such inactivation is not understood, nor is the function of Srx1. To address this question, we generated a mouse line with a null deletion of the Srx1-encoding Srxn1 gene. We show here that Srxn1(-/-) mice are perfectly viable and do not suffer from any apparent defects under laboratory conditions, but have an abnormal response to lipopolysaccharide that manifests by increased mortality during endotoxic shock. Microarray-based mRNA profiles show that although the response of Srxn1(-/-) mice to lipopolysaccharide is typical, spanning all spectrum and all pathways of innate immunity, it is delayed by several hours and remains intense when the response of Srxn1(+/+) mice has already dissipated. These data indicate that Srx1 activity protects mice from the lethality of endotoxic shock, adding this enzyme to other host factors, as NRF2 and peroxiredoxin 2, which by regulating cellular reactive oxygen species levels act as important modifiers in the pathogenesis of sepsis.
ano.nymous@ccsd.cnrs.fr.invalid (Anne-Gaëlle Planson) 16 Sep 2020
https://hal.inrae.fr/hal-02941029v1
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[hal-01606477] Unrecognized soil algal and cyanobacterial communities as a model, for herbicide risk assessment in agricultural soils
Unrecognized soil algal and cyanobacterial communities as a model, for herbicide risk assessment in agricultural soils. 1ère conférence internationale d’Ecotoxicologie Microbienne, EcotoxicoMic
ano.nymous@ccsd.cnrs.fr.invalid (Olivier Crouzet) 02 Jun 2020
https://hal.science/hal-01606477v1
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[hal-01606475] The significance of soil algae and cyanobacteria in agricultural soils, as a model of soil microbial communities, for the pesticide risk assessment
The significance of soil algae and cyanobacteria in agricultural soils, as a model of soil microbial communities, for the pesticide risk assessment. 7ème Conference on Pesticide Behaviour in Soils, Water and Air
ano.nymous@ccsd.cnrs.fr.invalid (Olivier Crouzet) 03 Oct 2017
https://hal.science/hal-01606475v1
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[hal-03708769] Discrimination of spoiled beef and salmon stored under different atmospheres by an optoelectronic nose. Comparison with GC-MS measurements
The aim of this study was to evaluate the capacity of an electronic nose, the NeOse Pro, to assess the alteration of two food matrixes of animal origin, beef and salmon. For each matrix, two types of samples were analyzed, natural samples and simplified "diluted " samples based on meat juice and agar. Samples were inoculated with specific spoilage organisms and stored for 6 days at 8°C under different conditions: air, modified atmosphere packaging, and vacuum packaging. A non-inoculated control sample was stored at-80°C under vacuum packaging. Results of the NeOse Pro were compared with gas chromatography coupled to mass spectrophotometry analysis. For this purpose, heatmaps, principal component analysis and discriminant analysis were used. GC-MS results show that the major detected volatile organic compounds for beef stored under air are dimethyl disulfide and ethyl acetate. For salmon stored under air, it was mainly dimethyl disulfide, methyl thioacetate, acetoin and ethyl acetate that were produced. For beef and salmon NeOse Pro and GC-MS results are consistent; samples stored under air are separated from other samples.
ano.nymous@ccsd.cnrs.fr.invalid (Pauline Claus) 29 Jun 2022
https://isara.hal.science/hal-03708769v1
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[hal-04666497] Purchases dominate the carbon footprint of research laboratories
Despite increasing interest for the carbon footprint of higher education institutions, little is known about the carbon footprint associated to research activities. Air travel and attendance to conferences concentrate recent data and debates but purchases have attracted little attention. Here we develop a hybrid method to estimate the greenhouse gas emissions (GHG) associated to research purchases. To do so, we combine macroeconomic databases, research-centered companies footprints and life-cycle assessments to construct a public database of monetary emission factors (EF) for research purchases. We apply it to estimate the purchases emissions of a hundred of research laboratories in France, belonging to the Labos 1point5 network and gathering more than 20000 staff, from all disciplines. We find that purchases dominate laboratory emissions, accounting for more than 50% of emissions, with a median of 2.7 t CO$_2$e/pers, which is 3 to 4-fold the separate contribution from travel, commutes and heating. Median electricity emissions are 5-fold lower in our dataset of laboratories using low carbon electricity but they become preponderant for high carbon electricity mixes (3.5 t CO$_2$e/pers). Purchases emissions are very heterogeneous among laboratories and are linearly correlated with budget, with an average carbon intensity of 0.31 ± 0.07 kg CO$_2$/€ and differences between research domains. Finally, we quantify the effect of a series of demand-driven mitigation strategies obtaining up to −20% in total emissions (−40% in purchases emissions), suggesting that effectively reducing the carbon footprint of research activities calls for systemic changes.
ano.nymous@ccsd.cnrs.fr.invalid (Marianne de Paepe) 01 Aug 2024
https://hal.science/hal-04666497v2
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[hal-04214482] Adlercreutzia equolifaciens Is an Anti-Inflammatory Commensal Bacterium with Decreased Abundance in Gut Microbiota of Patients with Metabolic Liver Disease
Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can lead to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observe that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy for liver diseases.
ano.nymous@ccsd.cnrs.fr.invalid (Florian Plaza Oñate) 13 Feb 2024
https://univ-angers.hal.science/hal-04214482v1
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[hal-04296502] Roseburia, a decreased bacterial taxon in the gut microbiota of patients suffering from anorexia nervosa
Anorexia nervosa (AN) is a severe eating disorder which can lead to malnutrition and life threatening complications with high mortality rates. We designed our analysis to identify gut microbial taxa differentially abundant between AN and HC across different 16S rRNA gene datasets. We identified a reduced abundance, diversity and richness of Roseburia genus in the microbiota of patients with AN. Cares leading to partial recovery of patients with AN during hospitalization did not restore Roseburia to the levels of HC. AN dietary habit, either purgative or restrictive, did not affect Roseburia abundance. Roseburia genus and related species abundance were correlated with different health host metabolic markers. Roseburia species are key functional taxa in the human gut microbiome. Low gut Roseburia levels have been linked with other human pathologies. Our study highlights Roseburia species as a major decreased component in the gut of patients with AN.
ano.nymous@ccsd.cnrs.fr.invalid (Stanislas Mondot) 20 Nov 2023
https://hal.inrae.fr/hal-04296502v1
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[hal-03973492] DOHaD22-ABS-1830 NEONATAL TRANSFER OF MATERNAL MICROBIOTA HAS A LASTING EFFECT ON THE FEEDING BEHAVIOR OF THE OFFSPRING
Introduction: The microbiome is known to impact nearly every aspect of host physiology in health and disease, as it has a substantial effect on metabolic function. Vertical transmission from mother to child can affect the physiology from one generation to the next when changes in the composition of the microbiota have occurred due to maternal diet or obesity. Objectives: Our objective was to study whether obesity or thinness during gestation and lactation would impact different maternal microbiota and whether the transfer of microbiota to the newborn would modify feeding behavior, independently of the metabolic alterations of the mother. We thus characterized the potential role of vertical transfers of maternal microbiota in the programming of offspring feeding behavior and studied the potential mechanisms underlying the programming. Methods: Selectively obesity-prone (OP)/obesity-resistant (OR) Sprague Dawley dams were used because differences in cultures of cecal microbiota and milk microbiota were demonstrated. Microbiota collected from the vagina, feces and milk were orally inoculated into conventional Fischer F344 recipient puppies from birth to 15 days to create 3 groups of puppies: F-OP, FOR and F-Sham. Results: Early transfer of maternal microbiota was associated with specific feeding behavior traits that predisposed F-OP rats to a higher risk of overconsumption in later periods of life. The metagenomic analysis allowed us to identify a few species and the corresponding metagenomic functions positively or negatively associated with the alteration of food intake parameters and the cerebral functional pathway. DGE seq analysis of brain structure, neuroanatomy features, and NMR analysis of plasma and intestinal contents of transferred animals were also studied to search for a potential mechanistic relationship between microbiome activity and brain development. Conclusion: These results support the idea that neonatal transfer of gut microbiota can program feeding behavior, probably by acting on early phases of neurodevelopment.
ano.nymous@ccsd.cnrs.fr.invalid (Patricia Parnet) 04 Feb 2023
https://hal.inrae.fr/hal-03973492v1
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[hal-03664919] Human CD4+/CD8α+ regulatory T cells induced by Faecalibacterium prausnitzii protect against intestinal inflammation
Faecalibacterium prausnitzii (F. prausnitzii), a dominant bacterium of the human microbiota, is decreased in patients with inflammatory bowel diseases (IBD) and exhibits anti-inflammatory effects. In human, colonic lamina propria contains IL-10-secreting, Foxp3-negative regulatory T cells (Treg) characterized by a double expression of CD4 and CD8α (DP8α) and a specificity for F. prausnitzii. This Treg subset is decreased in IBD. The in vivo effect of DP8α cells has not been evaluated yet. Here, using a humanized model of NOD.Prkcscid IL2rγ-/- (NSG) immunodeficient mouse strain that expresses the human leucocyte antigen D-related allele HLA-DR*0401 but not murine class II (NSG-Ab° DR4) molecules, we demonstrated a protective effect of a HLA-DR*0401-restricted DP8α Treg clone combined with F. prausnitzii administration in a colitis model. In a cohort of patients with IBD, we showed an independent association between the frequency of circulating DP8α cells and disease activity. Finally, we pointed out a positive correlation between F. prausnitzii-specific DP8α Tregs and the amount of F. prausnitzii in fecal microbiota in healthy individuals and patients with ileal Crohn's disease.
ano.nymous@ccsd.cnrs.fr.invalid (Sothea Touch) 05 Dec 2023
https://hal.science/hal-03664919v1
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[hal-04353544] An Insight into Functional Metagenomics: a High-Throughput Approach to Decipher Food–Microbiota–Host Interactions in the Human Gut
Our understanding of the symbiotic relationship between the microbiota and its host has constantly evolved since our understanding that the “self” was not only defined by our genetic patrimony but also by the genomes of bugs living in us. The first culture-based methods highlighted the important functions of the microbiota. However, these methods had strong limitations and did not allow for a full understanding of the complex relationships that occur at the interface between the microbiota and the host. The recent development of metagenomic approaches has been a groundbreaking step towards this understanding. Its use has provided new insights and perspectives. In the present chapter, we will describe the advances of functional metagenomics to decipher food–microbiota and host–microbiota interactions. This powerful high-throughput approach allows for the assessment of the microbiota as a whole (including non-cultured bacteria) and enabled the discovery of new signaling pathways and functions involved in the crosstalk between food, the gut microbiota and its host. We will present the pipeline and highlight the most important studies that helped to develop the field. To conclude, we will emphasize the most recent developments and hot topics in functional metagenomics.
ano.nymous@ccsd.cnrs.fr.invalid (Elliot Mathieu) 03 Jun 2024
https://hal.science/hal-04353544v1
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[hal-04579168] Prenatal maternal supplementation with prebiotics regulates microbiota colonization in high-risk children, but do not prevent atopic dermatitis at one year of age
[...]
ano.nymous@ccsd.cnrs.fr.invalid (Marie Bodinier) 17 May 2024
https://hal.science/hal-04579168v1
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[hal-03578742] Prebiotic Supplementation During Gestation Induces a Tolerogenic Environment and a Protective Microbiota in Offspring Mitigating Food Allergy
Food allergy is associated with alterations in the gut microbiota, epithelial barrier, and immune tolerance. These dysfunctions are observed within the first months of life, indicating that early intervention is crucial for disease prevention. Preventive nutritional strategies with prebiotics are an attractive option, as prebiotics such as galacto-oligosaccharides and inulin can promote tolerance, epithelial barrier reinforcement, and gut microbiota modulation. Nonetheless, the ideal period for intervention remains unknown. Here, we investigated whether galacto-oligosaccharide/inulin supplementation during gestation could protect offspring from wheat allergy development in BALB/cJRj mice. We demonstrated that gestational prebiotic supplementation promoted the presence of beneficial strains in the fecal microbiota of dams during gestation and partially during mid-lactation. This specific microbiota was transferred to their offspring and maintained to adulthood. The presence of B and T regulatory immune cell subsets was also increased in the lymph nodes of offspring born from supplemented mothers, suggestive of a more tolerogenic immune environment. Indeed, antenatal prebiotic supplementation reduced the development of wheat allergy symptoms in offspring. Our study thus demonstrates that prebiotic supplementation during pregnancy induces, in the offspring, a tolerogenic environment and a microbial imprint that mitigates food allergy development.
ano.nymous@ccsd.cnrs.fr.invalid (Amandine Selle) 14 Sep 2023
https://hal.inrae.fr/hal-03578742v1
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[hal-04989237] Effect of antimicrobial peptide Reg3γ on IBS-like symptoms following Citrobacter rodentium infection
[...]
ano.nymous@ccsd.cnrs.fr.invalid (V Daugey) 13 Mar 2025
https://hal.science/hal-04989237v1
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[hal-02306689] Probiotic Potential and Safety Evaluation of Enterococcus faecalis OB14 and OB15, Isolated From Traditional Tunisian Testouri Cheese and Rigouta, Using Physiological and Genomic Analysis
[...]
ano.nymous@ccsd.cnrs.fr.invalid (Olfa Baccouri) 02 Apr 2025
https://normandie-univ.hal.science/hal-02306689v1
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[hal-04011767] Fate, uptake and gut toxicity of two colloidal silver products in mice: how micro X-ray fluorescence, micro X-ray absorption spectroscopy and near-infrared spectroscopy provide new insights in food nanotoxicology
Silver biodistribution and gut toxicity of two commercially available colloidal silver products, Mesosilver™ and AgC, were evaluated in male mice. AgC is composed solely of ionic silver (Ag+) while Mesosilver™ contains a mix of silver nanoparticles (AgNPs) and Ag+ ions. After high-dose (approximately 3 mg per kg body weight (bw) per day) sub-chronic exposure, silver accumulation was close for Mesosilver™ and AgC. The combination of micro X-ray fluorescence and micro X-ray absorption spectroscopy showed that metallic AgNPs and Ag+ ions initially contained in Mesosilver™ were subjected to physicochemical modifications during their fate in the gut. In the colon, most Ag atoms were oxidized and dissolved to form Ag complexes with thiol groups (-SH) of proteins and/or peptides. Sub-chronic exposure at lower dose (150 μg per kg bw per day) led to a moderate impact on the gut barrier for both colloidal silver products. An increase in colonic LCN-2 was observed only after AgC exposure. For gut microbiota at the genus level, exposure to Mesosilver™ led to a decrease in Ruminococcus and Anaerosporobacter, while Intestinimonas increased. Exposure to AgC resulted in an increase in Clostridium sp. ASF356 and Tyzzerella, while the relative abundance of Anaerosporobacter decreased. In addition, the Saccharomycetes fungal population increased. Near-infrared spectroscopy was able to satisfactorily discriminate the Mesosilver™-vs. AgC-exposed mice for both exposure doses. This study highlights the applicability of biophysics-based methodologies for providing novel insights into colloidal silver uptake, fate and toxicological effects after oral exposure
ano.nymous@ccsd.cnrs.fr.invalid (Kevin Gillois) 02 Mar 2023
https://hal.inrae.fr/hal-04011767v1
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[hal-04649763] MAIT cells monitor intestinal dysbiosis and contribute to host protection during colitis
Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors and responds to such changes remains unclear. Here, we describe a protective mechanism by which mucosal-associated invariant T (MAIT) cells detect microbiota metabolites produced upon intestinal inflammation and promote tissue repair. At steady state, MAIT ligands derived from the riboflavin biosynthesis pathway were produced by aerotolerant bacteria residing in the colonic mucosa. Experimental colitis triggered luminal expansion of riboflavin-producing bacteria, leading to increased production of MAIT ligands. Modulation of intestinal oxygen levels suggested a role for oxygen in inducing MAIT ligand production. MAIT ligands produced in the colon rapidly crossed the intestinal barrier and activated MAIT cells, which expressed tissue-repair genes and produced barrier-promoting mediators during colitis. Mice lacking MAIT cells were more susceptible to colitis and colitis-driven colorectal cancer. Thus, MAIT cells are sensitive to a bacterial metabolic pathway indicative of intestinal inflammation.
ano.nymous@ccsd.cnrs.fr.invalid (Yara El Morr) 10 Oct 2024
https://hal.science/hal-04649763v1
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[hal-04670622] Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice
Tryptophan (Trp) is an essential amino acid, whose metabolism is a key gatekeeper of intestinal homeostasis. Yet, its systemic effects, particularly on atherosclerosis, remain unknown. Here we show that high-fat diet (HFD) increases the activity of intestinal indoleamine 2, 3-dioxygenase 1 (IDO), which shifts Trp metabolism from the production of microbiota-derived indole metabolites towards kynurenine production. Under HFD, the specific deletion of IDO in intestinal epithelial cells leads to intestinal inflammation, impaired intestinal barrier, augmented lesional T lymphocytes and atherosclerosis. This is associated with an increase in serotonin production and a decrease in indole metabolites, thus hijacking Trp for the serotonin pathway. Inhibition of intestinal serotonin production or supplementation with indole derivatives alleviates plaque inflammation and atherosclerosis. In summary, we uncover a pivotal role of intestinal IDO in the fine-tuning of Trp metabolism with systemic effects on atherosclerosis, paving the way for new therapeutic strategies to relieve gut-associated inflammatory diseases.
ano.nymous@ccsd.cnrs.fr.invalid (Mouna Chajadine) 12 Aug 2024
https://hal.inrae.fr/hal-04670622v1
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[hal-05019388] Mice lacking the fructose transporter Glut5 exhibit excessive androgens and reduced sperm motility
Overconsumption of fructose is linked to metabolic diseases, which are often associated with reduced fertility. GLUT5 is the most specific fructose transporter. To investigate its role in the testes, we analyzed the male reproductive phenotype of transgenic male mice deficient in GLUT5 (GLUT5−/− or GLUT5 knockout [KO] mice). Glut5 expression was shown in Leydig cells and germ cells, from primary spermatocytes to spermatozoa. We found reduced intratesticular fructose and pyruvate concentrations in GLUT5−/− mice. These mice exhibited 30% lower litter sizes compared with control mice. Histological analysis of the testes revealed some seminiferous tubules with a “Sertoli cell-only” phenotype, although spermatogenesis occurred normally in most tubules. Reduced fertility in GLUT5 KO mice was linked to lower sperm production and impaired sperm quality. Spermatozoa from these mice displayed reduced motility, head abnormalities, and a diminished acrosome reaction, which was associated with reduced cyclic adenosine monophosphate content and impaired phosphorylation of protein kinase A substrates in the acrosome. Unexpectedly, androgen production in GLUT5 KO mice was 3-fold higher than in controls, despite unchanged luteinizing hormone levels. Electron microscopy of Leydig cells revealed a highly developed smooth endoplasmic reticulum, increased lipid droplets, and abnormal mitochondrial structures, suggesting disrupted mitochondrial dynamics. Proteomic analysis identified 155 deregulated proteins in the testicular tissue of GLUT5 KO mice, nearly half of which were associated with sperm motility, germ cell morphology, glycolysis, mitochondrial dynamics, and oxidative stress. In conclusion, the absence of the specific fructose transporter GLUT5 reduced testicular fructose content and led to an asthenozoospermia phenotype accompanied by hyperandrogenism.
ano.nymous@ccsd.cnrs.fr.invalid (Aikaterini Kallianioti) 03 Apr 2025
https://hal.inrae.fr/hal-05019388v1
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[hal-01204439] Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding
Epidemiological observations report an increase in fat consumption associated with low intake of n-3 relative to n-6 polyunsaturated fatty acids (PUFAs) in women of childbearing age. However, the impact of these maternal feeding habits on cognitive function in the offspring is unknown. This study aims to investigate the impact of early exposure to a high-fat diet (HFD) with an unbalanced n-6/n-3 PUFAs ratio on hippocampal function in adult rats. Furthermore, we explored the effects of perinatal HFD combined with exposure to HFD after weaning. Dams were fed a control diet (C, 12% of energy from lipids, n-6/n-3 PUFAs ratio: 5) or HFD (HF, 39% of energy from lipids, n-6/n-3 PUFAs ratio: 39) throughout gestation and lactation. At weaning, offspring were placed either on control (C-C, HF-C) or high-fat (HF-HF) diets. In adulthood, hippocampus-dependent memory was assessed using the water-maze task and potential hippocampal alterations were determined by studying PUFA levels, gene expression, neurogenesis and astrocyte morphology. Perinatal HFD induced long-lasting metabolic alterations and some changes in gene expression in the hippocampus, but had no effect on memory. In contrast, spatial memory was impaired in animals exposed to HFD during the perinatal period and maintained on this diet. HF-HF rats also exhibited low n-3 and high n-6 PUFA levels, decreased neurogenesis and downregulated expression of several plasticity-related genes in the hippocampus. To determine the contribution of the perinatal diet to the memory deficits reported in HF-HF animals, an additional experiment was conducted in which rats were only exposed to HFD starting at weaning (C-HF). Interestingly, memory performance in this group was similar to controls. Overall, our results suggest that perinatal exposure to HFD with an unbalanced n-6/n-3 ratio sensitizes the offspring to the adverse effects of subsequent high-fat intake on hippocampal function.
ano.nymous@ccsd.cnrs.fr.invalid (Amandine L. Lepinay) 23 Sep 2015
https://hal.science/hal-01204439v1
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[hal-03171983] Dietary switch to Western diet induces hypothalamic adaptation associated with gut microbiota dysbiosis in rats
Background: Early hyperphagia and hypothalamic inflammation encountered after Western diet (WD) are linked to rodent propensity to obesity. Inflammation in several brain structures has been associated with gut dysbiosis. Since gut microbiota is highly sensitive to dietary changes, we hypothesised that immediate gut microbiota adaptation to WD in rats is involved in inflammation-related hypothalamic modifications. Methods: We evaluated short-term impact of WD consumption (2 h, 1, 2 and 4 days) on hypothalamic metabolome and caecal microbiota composition and metabolome. Data integration analyses were performed to uncover potential relationships among these three datasets. Finally, changes in hypothalamic gene expression in absence of gut microbiota were evaluated in germ-free rats fed WD for 2 days. Results: WD quickly and profoundly affected the levels of several hypothalamic metabolites, especially oxidative stress markers. In parallel, WD consumption reduced caecal microbiota diversity, modified its composition towards pro-inflammatory profile and changed caecal metabolome. Data integration identified strong correlations between gut microbiota sub-networks, unidentified caecal metabolites and hypothalamic oxidative stress metabolites. Germ-free rats displayed reduced energy intake and no changes in redox homoeostasis machinery expression or pro-inflammatory cytokines after 2 days of WD, in contrast to conventional rats, which exhibited increased SOD2, GLRX and IL-6 mRNA levels. Conclusion: A potentially pro-inflammatory gut microbiota and an early hypothalamic oxidative stress appear shortly after WD introduction. Tripartite data integration highlighted putative links between gut microbiota sub-networks and hypothalamic oxidative stress. Together with the absence of hypothalamic modifications in germ-free rats, this strongly suggests the involvement of the microbiota-hypothalamus axis in rat adaptation to WD introduction and in energy homoeostasis regulation.
ano.nymous@ccsd.cnrs.fr.invalid (Mélanie Fouesnard) 07 Sep 2021
https://hal.science/hal-03171983v1
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[hal-03222293] Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection
There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray–Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray–Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r2 = 0.17; p < 0.0001). The PCoA analysis of the Bray–Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.
ano.nymous@ccsd.cnrs.fr.invalid (Benoit Levast) 10 May 2021
https://hal.science/hal-03222293v1
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[hal-04297740] Avis de l'Anses relatif à l’actualisation des repères alimentaires du PNNS pour les enfants de 0 à 3 ans
Les bases scientifiques nécessaires à l’établissement des repères alimentaires du Programme National Nutrition Santé (PNNS) ont été actualisées par l’Anses en 2016 pour les hommes et femmes adultes sur la base des nouvelles références nutritionnelles et des données actuelles de consommation et de composition des aliments (Anses 2016b). Ces repères concernant la population générale, hommes et femmes adultes hors populations particulières, le Directeur général de la santé a saisi l’Anses le 12 juillet 2016 afin que des repères soient également énoncés pour les populations spécifiques que constituent les femmes enceintes et allaitantes, les enfants et adolescents et les personnes âgées et les femmes ménopausées. Le présent avis porte sur les enfants âgés de 0 à 3 ans.
ano.nymous@ccsd.cnrs.fr.invalid (François Mariotti) 21 Dec 2023
https://hal.inrae.fr/hal-04297740v1
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[hal-04314263] Avis de l'Anses relatif à l’actualisation des repères alimentaires du PNNS pour les femmes enceintes ou allaitantes
Les bases scientifiques nécessaires à l’établissement des repères du Programme National Nutrition Santé (PNNS) ont été actualisées par l’Anses en 2016 pour la population générale adulte sur la base des nouvelles références nutritionnelles et des données récentes de consommation et de composition des aliments (Anses 2016b). Par ailleurs, l’activité physique a été traitée dans le rapport « Actualisation des repères du PNNS - Révisions des repères relatifs à l’activité physique et à la sédentarité », saisine n°2012-SA-0155, publié en 2016 (Anses 2016c). L’actualisation des repères alimentaires en vigueur dans le cadre du précédent PNNS 2011-2015 pour la population des femmes enceintes ou allaitantes se fonde sur l’analyse des recommandations existantes dans d’autres pays et sur les relations épidémiologiques entre la consommation de groupes d’aliments et la santé des femmes enceintes ou allaitantes et de leur enfant. Le présent avis porte sur les femmes enceintes et allaitantes dont la grossesse ne présente pas de risque particulier et n’est pas qualifiée de pathologique. Les risques liés à la consommation d’alcool par les femmes enceintes ou allaitantes ne sont pas traités dans le cadre de cet avis car c’est une question spécifique, indépendante des autres facteurs alimentaires, qui a fait l’objet d’évaluation et de procédure de gestion récentes (Santé publique France 2017).
ano.nymous@ccsd.cnrs.fr.invalid (François Mariotti) 21 Dec 2023
https://hal.inrae.fr/hal-04314263v1
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[hal-03073792] Associations between untargeted plasma metabolomic signatures and gut microbiota composition in the Milieu Intérieur population of healthy adults
Host-microbial co-metabolism products are being increasingly recognized to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host-microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton nuclear magnetic resonance analysis of plasma. The associations between metabolomic variables and α- and β-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, PERMANOVAs, and MaAsLins, respectively. A Multiple testing correction was applied (Benjamini-Hochberg, 10%-FDR). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose, and citrate (-0.133 ≤ Spearman's ρ ≤ 0.126). Specific associations between metabolomic signals and abundances of taxa were detected (25 at the genus level and 19 at the species level): notably, numerous associations were observed for creatinine (positively associated with 11 species, and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host-gut microbiota metabolic relationships. In particular, our results support the implication of a "gut-kidney axis". More studies providing a detailed exploration of these complex interactions, and their implications for host health are needed.
ano.nymous@ccsd.cnrs.fr.invalid (Valentin Partula) 29 Dec 2020
https://hal.science/hal-03073792v1
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[hal-02790439] Avis de l'Anses relatif à l’actualisation des repères alimentaires du PNNS pour les enfants de 4 à 17 ans
Les bases scientifiques nécessaires à l’établissement des repères alimentaires du Programme National Nutrition Santé (PNNS) ont été actualisées par l’Anses en 2016 pour la population générale adulte sur la base des nouvelles références nutritionnelles et des données actuelles de consommation et de composition des aliment (Anses 2016d). Ces repères concernant la population générale, hommes et femmes adultes hors populations particulières, le Directeur général de la santé a saisi l’Anses le 12 juillet 2016 afin que des repères soient également énoncés pour les populations spécifiques que constituent les femmes enceintes et allaitantes, les enfants et adolescents et les personnes âgées et les femmes ménopausées. Le présent avis concerne la population spécifique des enfants âgés de 4 à 17 ans.
ano.nymous@ccsd.cnrs.fr.invalid (François Mariotti) 16 May 2024
https://hal.inrae.fr/hal-02790439v1
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[hal-03238372] Assessment of Neonatal Intensive Care Unit Practices and Preterm Newborn Gut Microbiota and 2-Year Neurodevelopmental Outcomes
Question What are the long-term outcomes associated with dysbiosis of gut microbiota in very preterm newborns? Findings In this cohort study of 577 very preterm newborns across 24 neonatal intensive care units from a French nationwide cohort, gut microbiota at week 4 after birth showed 6 bacterial patterns that varied according to gestational age, perinatal characteristics, individual treatments, and neonatal intensive care unit strategies. Three clusters were associated with 2-year outcomes after adjustment for these confounders. Meaning Modifying strategies associated with alterations in microbiota, such as promoting enteral nutrition, reducing sedation use, promoting early extubation, or skin-to-skin practice, may be correlated with outcomes in preterm newborns. This cohort study of 577 very preterm newborns across 24 neonatal intensive care units from a French nationwide cohort investigates associations among practice strategies, gut microbiota, and outcomes at 2 years. Importance In very preterm newborns, gut microbiota is highly variable with major dysbiosis. Its association with short-term health is widely studied, but the association with long-term outcomes remains unknown. Objective To investigate in preterm newborns the associations among practice strategies in neonatal intensive care units (NICUs), gut microbiota, and outcomes at 2 years. Design, Setting, and Participants EPIFLORE is a prospective observational cohort study that includes a stool sample collection during the fourth week after birth. Preterm newborns of less than 32 weeks of gestational age (GA) born in 2011 were included from 24 NICUs as part of the French nationwide population-based cohort, EPIPAGE 2. Data were collected from May 2011 to December 2011 and analyzed from September 2016 to December 2018. Exposures Eight NICU strategies concerning sedation, ventilation, skin-to-skin practice, antibiotherapy, ductus arteriosus, and breastfeeding were assessed. A NICU was considered favorable to a practice if the percentage of that practice in the NICU was more than the expected percentage. Main Outcomes and Measures Gut microbiota was analyzed by 16S ribosomal RNA gene sequencing and characterized by a clustering-based method. The 2-year outcome was defined by death or neurodevelopmental delay using a Global Ages and Stages questionnaire score. Results Of 577 newborns included in the study, the mean (SD) GA was 28.3 (2.0) weeks, and 303 (52.5%) were male. Collected gut microbiota was grouped into 5 discrete clusters. A sixth cluster included nonamplifiable samples owing to low bacterial load. Cluster 4 (driven by Enterococcus [n = 63]), cluster 5 (driven by Staphylococcus [n = 52]), and cluster 6 (n = 93) were significantly associated with lower mean (SD) GA (26.7 [1.8] weeks and 26.8 [1.9] weeks, respectively) and cluster 3 (driven by Escherichia/Shigella [n = 61]) with higher mean (SD) GA (29.4 [1.6] weeks; P = .001). Cluster 3 was considered the reference. After adjustment for confounders, no assisted ventilation at day 1 was associated with a decreased risk of belonging to cluster 5 or cluster 6 (adjusted odds ratio [AOR], 0.21 [95% CI, 0.06-0.78] and 0.19 [95% CI, 0.06-0.62], respectively) when sedation (AOR, 10.55 [95% CI, 2.28-48.87] and 4.62 [1.32-16.18], respectively) and low volume of enteral nutrition (AOR, 10.48 [95% CI, 2.48-44.29] and 7.28 [95% CI, 2.03-26.18], respectively) was associated with an increased risk. Skin-to-skin practice was associated with a decreased risk of being in cluster 5 (AOR, 0.14 [95% CI, 0.04-0.48]). Moreover, clusters 4, 5, 6 were significantly associated with 2-year nonoptimal outcome (AOR, 6.17 [95% CI, 1.46-26.0]; AOR, 4.53 [95% CI, 1.02-20.1]; and AOR, 5.42 [95% CI, 1.36-21.6], respectively). Conclusions and Relevance Gut microbiota of very preterm newborns at week 4 is associated with NICU practices and 2-year outcomes. Microbiota could be a noninvasive biomarker of immaturity.
ano.nymous@ccsd.cnrs.fr.invalid (Jean-Christophe Rozé) 27 May 2021
https://hal.inrae.fr/hal-03238372v1
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[inserm-02884679] Impact of pemetrexed chemotherapy on the gut microbiota and intestinal inflammation of patient-lung-derived tumor xenograft (PDX) mouse models
Chemotherapy remains the gold standard for advanced cancer. Pemetrexed, a chemotherapeutic agent used in non-small cell lung cancer, can induce significant side effects in patients. Although microbiota's role in the efficacy and/or toxicity of chemotherapy agents has been demonstrated, the impacts of pemetrexed on the gut microbiota and on gastrointestinal inflammation remain unknown. The objective of this study was to evaluate the impact of pemetrexed and the tumor graft on the gut microbiota composition in immunodeficient mice. The faecal microbiota composition was studied with metabarcoding before, 24-h and one week after treatment. The colon epithelial barrier integrity was evaluated by histological examination, intestinal permeability measurement, and selected cytokines quantification. The tumor graft induced some variations in the microbiota composition. Pemetrexed further increased the relative abundance of Enterobacteriaceae and 3 families from the Firmicutes phylum: Enterococcaceae, Lactobacillaceae and Streptococcaceae. Pemetrexed also significantly altered the epithelial barrier integrity, which was associated with early inflammation. This pilot study shows that the association of a lung tumor graft with pemetrexed causes an alteration in the microbiota composition. Such information increases our knowledge about the impact of chemotherapy on the microbiota, which could help to minimize side effects and improve therapeutic effectiveness in the future.
ano.nymous@ccsd.cnrs.fr.invalid (Cindy Pensec) 30 Jun 2020
https://inserm.hal.science/inserm-02884679v1
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[hal-02914960] Testing markers to characterize microbial communities in food ecosystems using a metagenomics approach
While metabarcoding is commonly used to describe prokaryotes in the microbiome of many environments, methods for describing micro-eukaryote diversity is lacking and requires better methodology and standardisation. One reason is that the universal fungal barcode, the Internal Transcribed Spacer (ITS) region, displays considerable size variation among yeasts and other micro-eukaryotes. There are also several repeats leading to sequencing errors or termination. Additionally, the ITS databases are far from complete, especially for Ascomycota that are commonly found in food. Other rDNA barcodes have been used but often do not harbor enough polymorphism to identify taxa at the Species level. In food, microbiota are usually composed of a reduced number of species compared to wild environments. Identifying micro-eukaryotes at the Species level, and potentially strain level, is therefore necessary.
ano.nymous@ccsd.cnrs.fr.invalid (Claire Vincent) 13 Aug 2020
https://hal.science/hal-02914960v1
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[hal-02623824] Multi-hit early life adversity affects gut microbiota, brain and behavior in a sex-dependent manner
The accumulation of adverse events in utero and during childhood differentially increases the vulnerability to psychiatric diseases in men and women. Gut microbiota is highly sensitive to the early environment and has been recently hypothesized to affect brain development. However, the impact of early-life adversity on gut microbiota, notably with regards to sex differences, remains to be explored. We examined the effects of multifactorial early-life adversity on behavior and microbiota composition in C3H/HeN mice of both sexes exposed to a combination of maternal immune activation (lipopolysaccharide injection on embryonic day 17, 120 μg/kg, i.p.), maternal separation (3hr per day from postnatal day (PND)2 to PND14) and maternal unpredictable chronic mild stress. At adulthood, offspring exposed to multi-hit early adversity showed sex-specific behavioral phenotypes with males exhibiting deficits in social behavior and females showing increased anxiety in the elevated plus maze and increased compulsive behavior in the marble burying test. Early adversity also differentially regulated gene expression in the medial prefrontal cortex (mPFC) according to sex. Interestingly, several genes such as Arc, Btg2, Fosb, Egr4 or Klf2 were oppositely regulated by early adversity in males versus females. Finally, 16S-based microbiota profiling revealed sex-dependent gut dysbiosis. In males, abundance of taxa belonging to Lachnospiraceae and Porphyromonadaceae families or other unclassified Firmicutes, but also Bacteroides, Lactobacillus and Alloprevotella genera was regulated by early adversity. In females, the effects of early adversity were limited and mainly restricted to Lactobacillus and Mucispirillum genera. Our work reveals marked sex differences in a multifactorial model of early-life adversity, both on emotional behaviors and gut microbiota, suggesting that sex should systematically be considered in preclinical studies both in neurogastroenterology and psychiatric research.
ano.nymous@ccsd.cnrs.fr.invalid (Marion Rincel) 25 Oct 2021
https://hal.inrae.fr/hal-02623824v1
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[hal-01160685] Detection, cloning, and distribution of minisatellites in some mammalian genomes.
The chromosomal distribution of minisatellites (cloned and/or detected using natural or synthetic tandem repeats) is strikingly different in man and mouse. In man, the vast majority is clustered in the terminal band of a subset of chromosome arms. Interestingly, the class of shorter tandem repeats called microsatellites is widespread along the chromosomes, suggesting that minisatellites can be created or maintained only in certain regions. In order to gain a better knowledge of these areas, we have studied a sub-telomeric cosmid from the pseudoautosomal region. Sixty kilobases of human genomic DNA starting approximately 20 kilobases from the human sex chromosomes telomere have previously been independently isolated in two cosmid clones (locus DXYS14) (Cooke et al., 1985); Rouyer et al., 1986). We have studied in more detail one of the two cosmids from this locus and found that it contains four different minisatellite structures representing 20 kilobases of the cosmid. These structures are unrelated to each other or to the minisatellite family described by Jeffreys et al. (1985). They display different degrees of polymorphism correlated with varying amounts of inner homogeneity. Combined with the previous description of an additional minisatellite (Cooke et al., 1985; Inglehearn and Cooke, 1990) in the contiguous cosmid, our observation shows that these structures may represent an important proportion of the DNA in sub-telomeric regions.
ano.nymous@ccsd.cnrs.fr.invalid (Gilles Vergnaud) 06 Jun 2015
https://ensta-paris.hal.science/hal-01160685v1
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[inserm-03547138] Cathepsin C inhibition as a potential treatment strategy in cancer
Epidemiological studies established an association between chronic inflammation and higher risk of cancer. Inhibition of proteolytic enzymes represents a potential treatment strategy for cancer and prevention of cancer metastasis. Cathepsin C (CatC) is a highly conserved lysosomal cysteine dipeptidyl aminopeptidase required for the activation of pro-inflammatory neutrophil serine proteases (NSPs, elastase, proteinase 3, cathepsin G and NSP-4). NSPs are locally released by activated neutrophils in response to pathogens and non-infectious danger signals. Activated neutrophils also release neutrophil extracellular traps (NETs) that are decorated with several neutrophil proteins, including NSPs. NSPs are not only NETs constituents but also play a role in NET formation and release. Although immune cells harbor large amounts of CatC, additional cell sources for this protease exists. Upregulation of CatC expression was observed in different tissues during carcinogenesis and correlated with metastasis and poor patient survival. Recent mechanistic studies indicated an important interaction of tumor-associated CatC, NSPs, and NETs in cancer development and metastasis and suggested CatC as a therapeutic target in a several cancer types. Cancer cell-derived CatC promotes neutrophil recruitment in the inflammatory tumor microenvironment. Because the clinical consequences of genetic CatC deficiency in humans resulting in the elimination of NSPs are mild, small molecule inhibitors of CatC are assumed as safe drugs to reduce the NSP burden. Brensocatib, a nitrile CatC inhibitor is currently tested in a phase 3 clinical trial as a novel anti-inflammatory therapy for patients with bronchiectasis. However, recently developed CatC inhibitors possibly have protective effects beyond inflammation. In this review, we describe the pathophysiological function of CatC and discuss molecular mechanisms substantiating pharmacological CatC inhibition as a potential strategy for cancer treatment.
ano.nymous@ccsd.cnrs.fr.invalid (Brice Korkmaz) 05 Jan 2024
https://inserm.hal.science/inserm-03547138v1
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[hal-02914082] Détermination de la souplesse hors plan d’un assemblage de composites boulonnés à l’aide d’une démarche d’homogénéisation
Dans de nombreux secteurs industriels, les matériaux composites tissés à fibres de carbone et matrices thermoplastiques semblent être une alternative prometteuse aux matériaux métalliques pour alléger les structures. Les matrices composites thermoplastiques ont un coût plus adapté à la fabrication de pièces composites avec de grandes cadences. Les assemblages de structures peuvent être des jonctions mécaniques à base de rivets, de vis ou de boulons. Dans cette étude, nous proposons de développer une approche expérimentale et numérique pour identifier les souplesses hors plan des constituants élémentaires d’un assemblage boulonné. Il n’y a actuellement aucune règle de conception pour prédire la rupture des liaisons boulonnées constituées de substrats composites thermoplastiques. Par conséquent, une étude expérimentale d’une liaison boulonnée utilisant la technique de corrélation d’images est présentée. Simultanément, des modèles éléments finis tridimensionnels d’assemblages associés à une approche d’équivalence en énergie ont été développés afin de déterminer la souplesse des éléments de l’assemblage. Ces modèles éléments finis ont ensuite été comparés avec succès à des résultats expérimentaux.
ano.nymous@ccsd.cnrs.fr.invalid (Laurent Gornet) 11 Aug 2020
https://hal.science/hal-02914082v1
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[inserm-01280941] CD4CD8aa Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease
How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL)-10-producing Foxp3 regulatory T cells (Treg), which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL) and peripheral blood lymphocytes (PBL) from healthy individuals, and those with colon cancer and irritable bowel disease (IBD), we demonstrated that CD4CD8aa (DP8a) T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8a LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8a PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i) uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii) identify F. prausnitzii as a major inducer of these Treg, (iii) argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv) provide new tools to address the systemic impact of both these Treg and the intestinal microbiota on the human immune homeostasis.
ano.nymous@ccsd.cnrs.fr.invalid (Guillaume Sarrabayrouse) 01 Mar 2016
https://inserm.hal.science/inserm-01280941v1
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[hal-03287046] Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment In Utero
The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.
ano.nymous@ccsd.cnrs.fr.invalid (Carole Brosseau) 15 Jul 2021
https://hal.inrae.fr/hal-03287046v1
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[hal-04314199] Avis de l'Anses relatif à l’actualisation des repères alimentaires du PNNS pour les femmes dès la ménopause et les hommes de plus de 65 ans
Les bases scientifiques nécessaires à l’établissement des repères alimentaires du Programme National Nutrition Santé (PNNS) ont été actualisées par l’Anses en 2016 pour la population générale adulte sur la base des nouvelles références nutritionnelles et des données actuelles de consommation et de composition des aliment (Anses 2016c). Ces repères concernant la population générale, hommes et femmes adultes hors populations particulières, le Directeur général de la santé a saisi l’Anses le 12 juillet 2016 afin que des repères soient également énoncés pour les populations spécifiques que constituent les femmes enceintes et allaitantes, les enfants et adolescents, les personnes âgées et les femmes ménopausées. Le présent avis concerne la population spécifique des femmes dès la ménopause et des hommes de plus de 65 ans.
ano.nymous@ccsd.cnrs.fr.invalid (François Mariotti) 21 Dec 2023
https://hal.inrae.fr/hal-04314199v1
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[hal-02024916] Faecalibacterium prausnitzii Skews Human DC to Prime IL10-Producing T Cells Through TLR2/6/JNK Signaling and IL-10, IL-27, CD39, and IDO-1 Induction
The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases.
ano.nymous@ccsd.cnrs.fr.invalid (Joudy Alameddine) 19 Feb 2019
https://hal.sorbonne-universite.fr/hal-02024916v1
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[hal-03281931] CSF concentration of cefotaxime in adult patients with pneumococcal meningitis: a multicentre retrospective study
Background and objectives - Pneumococcal meningitis is a devastating disease that requires adequate meningeal antibiotic penetration to limit the mortality. Despite a large usage in this indication, data about CSF concentration of cefotaxime during pneumococcal meningitis in adults are scarce. Therefore, we aimed to describe the CSF concentration obtained after high-dose cefotaxime administration in adult patients treated for Streptococcus pneumoniae meningitis. Patients and methods - In this multicentre, observational, retrospective study, cases of adult patients with S. pneumoniae meningitis hospitalized between January 2013 and October 2019 for whom cefotaxime concentration was measured in CSF were reviewed. Results - Cefotaxime concentration was analysed in 44 CSF samples collected among 31 patients. Median (IQR) age was 61 years (52-69). Dexamethasone was administered in 27 subjects. Median (IQR) cefotaxime daily dosage was 15 g (12-19), corresponding to 200 mg/kg (150-280). CSF samples were collected approximately 5 days after cefotaxime initiation. Median (IQR, range) cefotaxime CSF concentration was 10.3 mg/L (4.8-19.3, 1.2-43.4). Median (range) MIC for Streptococcus pneumoniae was 0.25 mg/L (0.008-1) (n = 22). The median (IQR, range) CSF/MIC ratio was 38 (12-146, 4-1844). Twenty-five CSF concentrations (81%) were above 10 times the MIC. Cefotaxime was discontinued in two patients for toxicity. In-hospital mortality rate was 29%. Conclusions - Adult patients with pneumococcal meningitis treated with a high dose of cefotaxime (200 mg/kg/day) had elevated CSF concentrations with satisfying pharmacokinetics/pharmacodynamics parameters and tolerability profile. This study brings reassuring pharmacological data regarding the use of high-dose cefotaxime monotherapy for treating pneumococcal meningitis with susceptible strains to cefotaxime.
ano.nymous@ccsd.cnrs.fr.invalid (Paul Le Turnier) 12 Jul 2021
https://hal.science/hal-03281931v1
