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[hal-04297503] Identification and Characterization of 33 Bacillus cereus sensu lato Isolates from Agricultural Fields from Eleven Widely Distributed Countries by Whole Genome Sequencing
The phylogeny, identification, and characterization of 33 B. cereus sensu lato isolates originating from 17 agricultural soils from 11 countries were analyzed on the basis of whole genome sequencing. Phylogenetic analyses revealed all isolates are divided into six groups, which follows the generally accepted phylogenetic division of B. cereus sensu lato isolates. Four different identification methods resulted in a variation in the identity of the isolates, as none of the isolates were identified as the same species by all four methods—only the recent identification method proposed directly reflected the phylogeny of the isolates. This points to the importance of describing the basis and method used for the identification. The presence and percent identity of the protein product of 19 genes potentially involved in pathogenicity divided the 33 isolates into groups corresponding to phylogenetic division of the isolates. This suggests that different pathotypes exist and that it is possible to differentiate between them by comparing the percent identity of proteins potentially involved in pathogenicity. This also reveals that a basic link between phylogeny and pathogenicity is likely to exist. The geographical distribution of the isolates is not random: they are distributed in relation to their division into the six phylogenetic groups, which again relates to different ecotypes with different temperature growth ranges. This means that we find it easier to analyze and understand the results obtained from the 33 B. cereus sensu lato isolates in a phylogenetic, patho-type and ecotype-oriented context, than in a context based on uncertain identification at the species level.
ano.nymous@ccsd.cnrs.fr.invalid (Athanasios Zervas) 06 Dec 2023
https://hal.inrae.fr/hal-04297503v1
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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-03795044] Effects of Five Filamentous Fungi Used in Food Processes on In Vitro and In Vivo Gut Inflammation
Food processes use different microorganisms, from bacteria to fungi. Yeast strains have been extensively studied, especially Saccharomyces cerevisiae. However, to date, very little is known about the potential beneficial effects of molds on gut health as part of gut microbiota. We undertook a comprehensive characterization of five mold strains, Penicillium camemberti, P. nalgiovense, P. roqueforti, Fusarium domesticum, and Geotrichum candidum used in food processes, on their ability to trigger or protect intestinal inflammation using in vitro human cell models and in vivo susceptibility to sodium dextran sulfate-induced colitis. Comparison of spore adhesion to epithelial cells showed a very wide disparity in results, with F. domesticum and P. roqueforti being the two extremes, with almost no adhesion and 20% adhesion, respectively. Interaction with human immune cells showed mild pro-inflammatory properties of all Penicillium strains and no effect of the others. However, the potential anti-inflammatory abilities detected for G. candidum in vitro were not confirmed in vivo after oral gavage to mice before and during induced colitis. According to the different series of experiments carried out in this study, the impact of the spores of these molds used in food production is limited, with no specific beneficial or harmful effect on the gut.
ano.nymous@ccsd.cnrs.fr.invalid (Maxime Poirier) 15 Feb 2024
https://hal.inrae.fr/hal-03795044v1
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[hal-02627696] The <em>bacillus cereus</em> Group: <em>bacillus</em> species with pathogenic potential
The Bacillus cereus group includes several Bacillus species with closely related phylogeny. The most well-studied members of the group, B. anthracis, B. cereus, and B. thuringiensis, are known for their pathogenic potential. Here, we present the historical rationale for speciation and discuss shared and unique features of these bacteria. Aspects of cell morphology and physiology, and genome sequence similarity and gene synteny support close evolutionary relationships for these three species. For many strains, distinct differences in virulence factor synthesis provide facile means for species assignment. B. anthracis is the causative agent of anthrax. Some B. cereus strains are commonly recognized as food poisoning agents, but strains can also cause localized wound and eye infections as well as systemic disease. Certain B. thuringiensis strains are entomopathogens and have been commercialized for use as biopesticides, while some strains have been reported to cause infection in immunocompromised individuals. In this article we compare and contrast B. anthracis, B. cereus, and B. thuringiensis, including ecology, cell structure and development, virulence attributes, gene regulation and genetic exchange systems, and experimental models of disease.
ano.nymous@ccsd.cnrs.fr.invalid (Monika Ehling-Schulz) 03 Jul 2025
https://hal.inrae.fr/hal-02627696v1
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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-05137649] Effect of bacterial nanocellulose and plant-containing facial serum on hyperpigmentation in in-vitro conditions
This study investigated the effect of some herbal extracts, such as licorice root, white mulberry leaf, green tea leaf, and grape seed, with a combination of bacterial nanocellulose and some bioactive materials, such as ascorbic acid, niacinamide, hexylresorcinol, and alpha-arbutin, on treatment of hyperpigmentation. The effect of the prepared emulsions on hyperpigmentation was revealed by analyzing their tyrosinase inhibition properties, their ability to stop melanin production, or their properties of whitening the brown spot on the skin. In addition to the physicochemical properties of the 5 different emulsions obtained, tyrosinase, collagenase, and elastase enzyme activities, antioxidant properties, cytotoxicity, and microbiological analyzes were performed by cell-culture modelling. Finally, a dermocosmetic facial serum was designed that is compatible with skin pH, is homogeneously mixed, has good spreading properties, does not cause any microbiological growth, does not inhibit elastase activity while stimulating collagenase activity, reduces melanin production by inhibiting the tyrosinase enzyme, and does not have any toxic effects.
ano.nymous@ccsd.cnrs.fr.invalid (Sibel Dikmen Kucuk) 01 Jul 2025
https://hal.science/hal-05137649v1
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[hal-05137331] Lower gut microbiota diversity is associated with higher susceptibility of BALB/c mice to allergic sensitization
Lower gut microbiota diversity is associated with higher susceptibility of BALB/c mice to allergic sensitization. Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology
ano.nymous@ccsd.cnrs.fr.invalid (Matieny Dite Aicha Maiga) 01 Jul 2025
https://hal.science/hal-05137331v1
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[hal-04565318] Duplex-specific nuclease assisted magnetic nanoprobe for cyclic amplified RNA detection
The recent spreading of viral diseases has led to the outbreak of pandemic and caused severe threats to public health worldwide. Though various approaches have been developed to detect viruses, there have only been a few reports on detecting viral RNA by cyclic signal amplification techniques. In search of an easy, cost-effective alternate method of gold-standard polymerase chain reaction (PCR), here, we have developed a duplexspecific nuclease (DSN)-based signal amplification method for RNA detection designing specific ssDNA-based nanoprobes. In the presence of target RNA under optimized conditions, DSN cleaves specifically the ssDNA in the DNA-RNA heteroduplex of the sensor to release the fluorophore from its quenched state while leaving the RNA strand free to react with another available nanoprobe for cyclic amplification. In this process, a single target RNA can interact with large numbers of nanoprobes, releasing amplified fluorophores from the core of the nanoprobes and increasing the fluorescence. The low detection limit of 11.5 fM has been achieved for a shortchain target RNA, indicating its potential application for the rapid RNA detection.
ano.nymous@ccsd.cnrs.fr.invalid (Malabika Ghosh) 01 May 2024
https://hal.inrae.fr/hal-04565318v1
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[hal-02490073] Biocatalytic production of energetic molecules from renewable resources for aviation fuel
Biocatalytic production of energetic molecules from renewable resources for aviation fuel. Eucass European Conference for Aerospace Sciences
ano.nymous@ccsd.cnrs.fr.invalid (Julien Cescut) 24 Feb 2020
https://hal.science/hal-02490073v1
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[hal-02626272] Enteric delivery of regenerating family member 3 alpha alters the intestinal microbiota and controls inflammation in mice with colitis
BACKGROUND & AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic (TG) expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice. METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter. In these mice, hREG3A travels via the bile to the intestinal lumen. Some mice were given dextran sodium sulfate (DSS) to induce colitis. Feces were collected from mice and the composition of the microbiota was analyzed by 16S ribosomal RNA sequencing. The fecal microbiome was also analyzed from mice that express only 1 copy of human REG3A transgene but were fed feces from control mice (not expressing hREG3A) as newborns. Mice expressing hREG3A were monitored for DSS-induced colitis after co-housing or feeding feces from control mice. Colitis was induced in another set of control and hREG3A-TG mice by administration of trinitrobenzene sulfonic acid; some mice were given intrarectal injections of the hREG3A protein. Colon tissues were collected from mice and analyzed by histology and immunohistochemistry to detect mucin 2, as well as by 16S ribosomal RNA fluorescence in situ hybridization, transcriptional analyses, and quantitative polymerase chain reaction. We measured levels of reactive oxygen species (ROS) in bacterial cultures and fecal microbiota using 20,70-dichloro-fluorescein diacetate and flow cytometry. RESULTS: The fecal microbiota of mice that express hREG3A had a significant shift in composition, compared with control mice, with enrichment of Clostridiales (Ruminococcaceae, Lachnospiraceae) and depletion of Bacteroidetes (Prevotellaceae); the TG mice developed less-severe colitis following administration of DSS than control mice, associated with preserved gut barrier integrity and reduced bacterial translocation, epithelial inflammation, and oxidative damage. A similar shift in the composition of the fecal microbiota occurred after a few months in TG mice heterozygous for REG3A that harbored a wild-type maternal microbiota at birth; these mice developed less-severe forms of colitis following DSS administration. Cohoused and germ-free mice fed feces from REG3A-TG mice and given DSS developed less-severe forms of colitis and had reduced lipopolysaccharide activation of the toll-like receptor 4 and increased survival times compared with mice not fed feces from REG3A-TG mice. REG3A TG mice developed only mild colonic inflammation after exposure to 2,4,6-trinitrobenzene sulfonic acid, compared with control mice. Control mice given intrarectal hREG3A and exposed to 2,4,6-trinitrobenzene sulfonic acid showed less colon damage and inflammation than mice not given intrarectal hREG3A. Fecal samples from REG3A-TG mice had lower levels of ROS than feces from control mice during DSS administration. Addition of hREG3A to bacterial cultures reduced levels of ROS and increased survival of oxygen-sensitive commensal bacteria (Faecalibacterium prausnitzii and Roseburia intestinalis). CONCLUSIONS: Mice with hepatocytes that express hREG3A, which travels to the intestinal lumen, are less sensitive to colitis than control mice. We found hREG3A to alter the colonic microbiota by decreasing levels of ROS. Fecal microbiota from REG3A-TG mice protect non-TG mice from induction of colitis. These findings indicate a role for reduction of oxidative stress in preserving the gut microbiota and its ability to prevent inflammation.
ano.nymous@ccsd.cnrs.fr.invalid (Marion Darnaud) 12 Jul 2021
https://hal.inrae.fr/hal-02626272v1
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[hal-01204281] Metagenomic species profiling using universal phylogenetic marker genes
To quantify known and unknown microorganisms at species-level resolution using shotgun sequencing data, we developed a method that establishes metagenomic operational taxonomic units (mOTUs) based on single-copy phylogenetic marker genes. Applied to 252 human fecal samples, the method revealed that on average 43% of the species abundance and 58% of the richness cannot be captured by current reference genome-based methods. An implementation of the method is available at http://www.bork.embl.de/software/mOTU/.
ano.nymous@ccsd.cnrs.fr.invalid (Shinichi Sunagawa) 23 Sep 2015
https://hal.science/hal-01204281v1
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[hal-01195478] An integrated catalog of reference genes in the human gut microbiome
Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) comprising 9,879,896 genes. The catalog includes close-to-complete sets of genes for most gut microbes, which are also of considerably higher quality than in previous catalogs. Analyses of a group of samples from Chinese and Danish individuals using the catalog revealed country-specific gut microbial signatures. This expanded catalog should facilitate quantitative characterization of metagenomic, metatranscriptomic and metaproteomic data from the gut microbiome to understand its variation across populations in human health and disease.
ano.nymous@ccsd.cnrs.fr.invalid (Junhua Li) 07 Sep 2015
https://hal.science/hal-01195478v1
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[hal-01594855] Human gut microbes impact host serum metabolome and insulin sensitivity
Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatusare identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
ano.nymous@ccsd.cnrs.fr.invalid (Helle Krogh Pedersen) 26 Sep 2017
https://hal.science/hal-01594855v1
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[hal-02641529] Dietary modulation of gut microbiota contributes to alleviation of both genetic and simple obesity in children
Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Ourmulti-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. Research in context: Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.
ano.nymous@ccsd.cnrs.fr.invalid (Chenhong Zhang) 28 May 2020
https://hal.inrae.fr/hal-02641529v1
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[hal-03649183] Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported1,2. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis3,4. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa3,4. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.
ano.nymous@ccsd.cnrs.fr.invalid (Kristoffer Forslund) 22 Apr 2022
https://hal.science/hal-03649183v1
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[cea-00908974] A human gut microbial gene catalogue established by metagenomic sequencing
To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, ~150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively
ano.nymous@ccsd.cnrs.fr.invalid (Junjie Qin) 16 Oct 2019
https://cea.hal.science/cea-00908974v1
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[hal-01190602] Richness of human gut microbiome correlates with metabolic markers
We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
ano.nymous@ccsd.cnrs.fr.invalid (Emmanuelle Le Chatelier) 18 Mar 2024
https://hal.science/hal-01190602v1
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[hal-05133447] Microbiome testing in Europe: navigating analytical, ethical and regulatory challenges
<div><p>Background In recent years, human microbiome research has flourished and has drawn attention from both healthcare professionals and general consumers as the human microbiome is now recognized as having a significant influence on human health. This has led to the emergence of companies offering microbiome testing services. Some of these services are sold directly to the consumer via companies' websites or via medical laboratory websites.</p></div> <div>Methodology<p>In order to provide an overview of the consumer experience proposed by these microbiome testing services, one single faecal sample was sent to six different companies (five based in Europe and one based in the USA). Two out of the six testing kits were commercialized by medical laboratories, but without any requirement for a medical prescription. The analyses and reports received were discussed with a panel of experts (21 experts from 8 countries) during an online workshop.</p></div> <div>Results<p>This workshop led to the identification of several limitations and challenges related to these kits, including over-promising messages from the companies, a lack of transparency in the methodology used for the analysis and a lack of reliability of the results. The experts considered the interpretations and recommendations provided in the different reports to be premature due to the lack of robust scientific evidence and the analyses associated with the reports to be of limited clinical utility. The experts also discussed the grey areas surrounding the regulatory status of these test kits, including their positioning in the European market. The experts recommended a distinction between regulatory requirements based on the intended use or purpose of the kit: on the one hand, test kits developed to satisfy consumer curiosity, with a clear mention of this objective, and no mention of any disease or risk of disease, and on the other hand, in vitro diagnostic (IVD) CE-marked test kits, which could go deeper into the analysis and interpretation of samples, as such a report would be intended for trained healthcare professionals.</p><p>Conclusions Recommendations or actions, specific to the context of use of microbiome testing kits, are listed to improve the quality and the robustness of these test kits to meet expectations of end users (consumers, patients and healthcare professionals). The need for standardization, robust scientific evidence, qualification of microbiomebased biomarkers and a clear regulatory status in Europe are the main issues that will require attention in the near future to align laboratory development with societal needs and thus foster translation into daily health practice.</p></div>
ano.nymous@ccsd.cnrs.fr.invalid (Julie Rodriguez) 27 Jun 2025
https://hal.science/hal-05133447v1
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[hal-01535324] Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported(1,2). In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis(3,4). Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa(3,4). These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.
ano.nymous@ccsd.cnrs.fr.invalid (Kristoffer Forslund) 08 Jun 2017
https://hal.science/hal-01535324v1
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[hal-03041270] Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
ano.nymous@ccsd.cnrs.fr.invalid (Pierre Bel Lassen) 12 Jan 2021
https://cnrs.hal.science/hal-03041270v2
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[hal-01195477] Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes
Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.
ano.nymous@ccsd.cnrs.fr.invalid (H Bjørn Nielsen) 07 Sep 2015
https://hal.science/hal-01195477v1
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[pasteur-01977322] Minimum Information about an Uncultivated Virus Genome (MIUViG)
We present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative studies and a systematic exploration of the global virosphere.
ano.nymous@ccsd.cnrs.fr.invalid (Simon Roux) 10 Jan 2019
https://pasteur.hal.science/pasteur-01977322v1
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[hal-01533942] Transcriptional interactions suggest niche segregation among microorganisms in the human gut
The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species(1). Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species(2,3). To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H-2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.
ano.nymous@ccsd.cnrs.fr.invalid (Damian Rafal Plichta) 06 Jun 2017
https://hal.science/hal-01533942v1
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[hal-03825727] Le microbiote intestinal comme marqueur potentiel du cancer colorectal
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ano.nymous@ccsd.cnrs.fr.invalid (Julien Tap) 23 Oct 2022
https://hal.inrae.fr/hal-03825727v1
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[hal-03342950] Cobalamin Scarcity Modifies Carbon Allocation and Impairs DMSP Production Through Methionine Metabolism in the Haptophyte Microalgae Tisochrysis lutea
Cobalamin (vitamin B-12) is a cobalt-containing enzymatic cofactor involved in methionine synthesis. Provided only by select bacteria and archaea in marine systems, this vitamin is known to limit primary production in different oceanic areas. Understanding the consequences of cobalamin limitation on phytoplankton physiology is of great interest, notably for cobalamin-dependent haptophytes that significantly contribute to oceanic carbon fixation and sulfur cycle through dimethyl sulfonio propionate (DMSP) synthesis. Here, the effect of cobalamin limitation was compared to nitrogen limitation on the model haptophyte Tisochrysis lutea grown in chemostats, combining comparative proteomics with the analysis of major macromolecules and specific osmolytes. Our results highlight the interconnection of carbon and DMSP metabolisms through the cobalamin-dependent methionine synthesis by showing that cobalamin scarcity impacts the mechanisms of carbon allocation and reduces DMSP quota. Conversely, proline production seemed to anticorrelate with cobalamin availability. In a boarder context, analysis of transcriptomes or genomes of main DMSP producers from different phytoplankton lineages suggests that most of them are cobalamin-dependent, which means that prokaryotic cobalamin synthesis exerts an important control on phytoplankton DMSP production in some regions of the world ocean.
ano.nymous@ccsd.cnrs.fr.invalid (Charlotte Nef) 13 Sep 2021
https://hal.inrae.fr/hal-03342950v1
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[hal-03290801] The Epistemic Revolution Induced by Microbiome Studies: An Interdisciplinary View
Many separate fields and practices nowadays consider microbes as part of their legitimate focus. Therefore, microbiome studies may act as unexpected unifying forces across very different disciplines. Here, we summarize how microbiomes appear as novel major biological players, offer new artistic frontiers, new uses from medicine to laws, and inspire novel ontologies. We identify several convergent emerging themes across ecosystem studies, microbial and evolutionary ecology, arts, medicine, forensic analyses, law and philosophy of science, as well as some outstanding issues raised by microbiome studies across these disciplines and practices. An ‘epistemic revolution induced by microbiome studies’ seems to be ongoing, characterized by four features: (i) an ecologization of pre-existing concepts within disciplines, (ii) a growing interest in systemic analyses of the investigated or represented phenomena and a greater focus on interactions as their root causes, (iii) the intent to use openly multi-scalar interaction networks as an explanatory framework to investigate phenomena to acknowledge the causal effects of microbiomes, (iv) a reconceptualization of the usual definitions of which individuals are worth considering as an explanans or as an explanandum by a given field, which result in a fifth strong trend, namely (v) a de-anthropocentrification of our perception of the world.
ano.nymous@ccsd.cnrs.fr.invalid (Eric Bapteste) 19 Jul 2021
https://hal.sorbonne-universite.fr/hal-03290801v1
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[hal-04940845] Real-time multimodal imaging of daptomycin action on the cell wall of adherent Staphylococcus aureus
Objectives: This study investigated the efficacy of daptomycin against adherent Staphylococcus aureus (S. aureus), a common colonizer of medical devices that leads to severe infections. For the first time, we evaluated the bactericidal effects of daptomycin on S. aureus immediately after adhesion, mimicking early-stage contamination of biomaterials. Time-kill curve assay and confocal laser scanning microscopy (CLSM) were used to analyze the process dynamics. In addition, atomic force microscopy (AFM) and scanning electron microscopy (SEM) were employed to elucidate daptomycin-induced structural changes in the bacterial cell wall. Results description: Daptomycin, at clinically relevant concentrations, rapidly eradicated adherent bacteria in the exponential growth phase, demonstrating an efficiency comparable to its action against planktonic cells. Prolonged exposure to the antibiotic caused marked alterations in the bacterial cell wall, including surface roughening and perforation, as revealed by multimodal imaging. However, daptomycin effectiveness diminished as biofilm formation progressed, underscoring the need for further exploration of optimized clinical strategies.
ano.nymous@ccsd.cnrs.fr.invalid (Alexis Canette) 11 Feb 2025
https://hal.science/hal-04940845v1
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[hal-04764203] Outcomes of Enterococcus faecalis infective endocarditis according to MIC of amoxicillin: a multicentric study
Abstract Background The incidence of Enterococcus faecalis infective endocarditis is increasing over time. Data on the impact of minimum inhibitory concentration (MIC) of amoxicillin on treatment outcomes are scarce. The objective of this study was to describe the epidemiology of E. faecalis infective endocarditis and to evaluate whether the MIC of amoxicillin might influence mortality. Materials We retrospectively included all consecutive patients diagnosed with definite E. faecalis infective endocarditis between 2013 and 2020 in 11 French hospitals. We extracted data from the local diagnosis-related group (DRG) database and matched these data with microbiological results. Amoxicillin MIC was determined by Etest strip. The primary endpoints were endocarditis-related mortality and risk factors for endocarditis-related mortality including amoxicillin MIC. Results A total of 403 patients with definite E. faecalis infective endocarditis were included. Patients were predominantly male (76.4%) with a median age of 74 years (67–82). Embolic complications occurred in 170 (42.1%) patients. Cardiac surgery was performed in 158 (61.5%) patients. The endocarditis-related mortality rate was 28.3% and the median delay between mortality and onset of hospitalization was 24 (9; 41) days. E. faecalis MIC of amoxicillin was available for 246 (61%) patients. The median MIC was 0.5 mg/L (0.4–0.7). Amoxicillin MIC was not found to be associated with in-hospital mortality. None of the variables included in the multivariate model were identified as a risk factor for mortality and there was no correlation between mortality and the duration of treatment for 4 weeks versus 6 weeks. Conclusions Higher amoxicillin MIC was not a risk factor leading to endocarditis-related mortality in definite E. faecalis infective endocarditis. However, further studies are needed to assess the effect of amoxicillin MIC on relapse.
ano.nymous@ccsd.cnrs.fr.invalid (Hermann Do Rego) 08 Nov 2024
https://hal.inrae.fr/hal-04764203v1
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[hal-03906694] Activation of class 1 integron integrase is promoted in the intestinal environment
Class 1 integrons are widespread genetic elements playing a major role in the dissemination of antibiotic resistance. They allow bacteria to capture, express and exchange antibiotic resistance genes embedded within gene cassettes. Acquisition of gene cassettes is catalysed by the class 1 integron integrase, a site-specific recombinase playing a key role in the integron system. In in vitro planktonic culture, expression of intI1 is controlled by the SOS response, a regulatory network which mediates the repair of DNA damage caused by a wide range of bacterial stress, including antibiotics. However, in vitro experimental conditions are far from the real lifestyle of bacteria in natural environments such as the intestinal tract which is known to be a reservoir of integrons. In this study, we developed an in vivo model of intestinal colonization in gnotobiotic mice and used a recombination assay and quantitative real-time PCR, to investigate the induction of the SOS response and expression and activity of the class 1 integron integrase, IntI1. We found that the basal activity of IntI1 was higher in vivo than in vitro . In addition, we demonstrated that administration of a subinhibitory concentration of ciprofloxacin rapidly induced both the SOS response and intI1 expression that was correlated with an increase of the activity of IntI1. Our findings show that the gut is an environment in which the class 1 integron integrase is induced and active, and they highlight the potential role of integrons in the acquisition and/or expression of resistance genes in the gut, particularly during antibiotic therapy.
ano.nymous@ccsd.cnrs.fr.invalid (Murielle Baltazar) 20 Dec 2022
https://hal.science/hal-03906694v1
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[hal-04535964] Biofilm formation of the food spoiler Brochothrix thermosphacta on different industrial surface materials using a biofilm reactor
Brochothrix thermosphacta is considered as a major food spoiler bacteria. This study evaluates biofilm formation by B. thermosphacta CD337(2) - a strong biofilm producer strain - on three food industry materials (polycarbonate (PC), polystyrene (PS), and stainless steel (SS)). Biofilms were continuously grown under flow at 25 degrees C in BHI broth in a modified CDC biofilm reactor. Bacterial cells were enumerated by plate counting, and biofilm spatial organization was deciphered by combining confocal laser scanning microscopy and image analysis. The biofilms had the same growth kinetics on all three materials and reach 8log CFU/cm2 as maximal concentration. Highly structured biofilms were observed on PC and PS, but less structured ones on SS. This difference was confirmed by structural quantification analysis using the image analysis software tool BiofilmQ. Biofilm on SS show less roughness, density, thickness and volume. The biofilm 3D structure seemed to be related to the coupon topography and roughness. The materials used in this study do not affect biofilm growth. However, their roughness and topography affect the biofilm architecture, which could influence biofilm behaviour.
ano.nymous@ccsd.cnrs.fr.invalid (Antoine Gaillac) 07 Apr 2024
https://hal.inrae.fr/hal-04535964v1
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[hal-04571280] Galf-Specific Neolectins: Towards Promising Diagnostic Tools
In the absence of naturally available galactofuranose-specific lectin, we report herein the bioengineering of GalNeoLect, from the first cloned wild-type galactofuranosidase ( sp. strain JHA19), which recognises and binds a single monosaccharide that is only related to nonmammalian species, usually pathogenic microorganisms. We kinetically characterised the GalNeoLect to confirm attenuation of hydrolytic activity and used competitive inhibition assay, with close structural analogues of Gal, to show that it conserved interaction with its original substrate. We synthetised the bovine serum albumin-based neoglycoprotein (GalNGP), carrying the multivalent Gal units, as a suitable ligand and high-avidity system for the recognition of GalNeoLect which we successfully tested directly with the galactomannan spores of (ATCC 16404). Altogether, our results indicate that GalNeoLect has the necessary versatility and plasticity to be used in both research and diagnostic lectin-based applications.
ano.nymous@ccsd.cnrs.fr.invalid (Mateja Senicar) 24 Sep 2024
https://hal.science/hal-04571280v1
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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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[insu-01461688] Comparison of biofilm formation and motility processes in arsenic-resistant Thiomonas spp. strains revealed divergent response to arsenite
Bacteria of the genus Thiomonas are found ubiquitously in arsenic contaminated waters such as acid mine drainage (AMD), where they contribute to the precipitation and the natural bioremediation of arsenic. In these environments, these bacteria have developed a large range of resistance strategies among which the capacity to form particular biofilm structures. The biofilm formation is one of the most ubiquitous adaptive response observed in prokaryotes to various stresses, such as those induced in the presence of toxic compounds. This study focused on the process of biofilm formation in three Thiomonas strains (CB1, CB2 and CB3) isolated from the same AMD. The results obtained here show that these bacteria are all capable of forming biofilms, but the architecture and the kinetics of formation of these biofilms differ depending on whether arsenite is present in the environment and from one strain to another. Indeed, two strains favoured biofilm formation, whereas one favoured motility in the presence of arsenite. To identify the underlying mechanisms, the patterns of expression of some genes possibly involved in the process of biofilm formation were investigated in Thiomonas sp. CB2 in the presence and absence of arsenite, using a transcriptomic approach (RNA-seq). The findings obtained here shed interesting light on how the formation of biofilms, and the motility processes contribute to the adaptation of Thiomonas strains to extreme environments.
ano.nymous@ccsd.cnrs.fr.invalid (Julien Farasin) 08 Feb 2017
https://insu.hal.science/insu-01461688v1
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[hal-01906028] Genetic deficiency of Indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health
The association between altered gut microbiota, intestinal permeability, inflammation and cardiometabolic diseases is becoming increasingly clear but remains poorly understood1,2. Indoleamine 2,3-dioxygenase is an enzyme induced in many types of immune cells, including macrophages in response to inflammatory stimuli, and catalyzes the degradation of tryptophan along the kynurenine pathway. Indoleamine 2,3-dioxygenase activity is better known for its suppression of effector T cell immunity and its activation of regulatory T cells3,4. However, high indoleamine 2,3-dioxygenase activity predicts worse cardiovascular outcome5,6,7,8,9 and may promote atherosclerosis and vascular inflammation6, suggesting a more complex role in chronic inflammatory settings. Indoleamine 2,3-dioxygenase activity is also increased in obesity10,11,12,13, yet its role in metabolic disease is still unexplored. Here, we show that obesity is associated with an increase of intestinal indoleamine 2,3-dioxygenase activity, which shifts tryptophan metabolism from indole derivative and interleukin-22 production toward kynurenine production. Indoleamine 2,3-dioxygenase deletion or inhibition improves insulin sensitivity, preserves the gut mucosal barrier, decreases endotoxemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. These beneficial effects are due to rewiring of tryptophan metabolism toward a microbiota-dependent production of interleukin-22 and are abrogated after treatment with a neutralizing anti-interleukin-22 antibody. In summary, we identify an unexpected function of indoleamine 2,3-dioxygenase in the fine tuning of intestinal tryptophan metabolism with major consequences on microbiota-dependent control of metabolic disease, which suggests indoleamine 2,3-dioxygenase as a potential therapeutic target.
ano.nymous@ccsd.cnrs.fr.invalid (Ludivine Laurans) 26 Oct 2018
https://hal.sorbonne-universite.fr/hal-01906028v1
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[hal-02565128] Three distinct glycosylation pathways are involved in the decoration of $Lactococcus\ lactis$ cell wall glycopolymers
Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.
ano.nymous@ccsd.cnrs.fr.invalid (Ilias Theodorou) 12 Jan 2024
https://hal.science/hal-02565128v1
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[anses-04027039] Évaluation des risques liés à la consommation de nitrates et nitrites
Le contexte de cette expertise est présenté ci-après selon les termes de la saisine émanant de la DGAL, la DGS et la DGCCRF . « La présence de nitrites dans l’organisme peut conduire à l’oxydation de l'hémoglobine réduisant la capacité des globules rouges à transporter l'oxygène. Elle peut également contribuer à la formation d’autres composés, tels que les nitrosamines, dont certains sont cancérogènes. Il existe différentes sources d’exposition des consommateurs aux nitrites et notamment : i) La conversion de nitrates présents dans certaines denrées alimentaires, en nitrites. Les nitrates se retrouvent dans l'eau notamment en raison de leur utilisation en production primaire. Ils sont naturellement présents dans certaines denrées alimentaires, en particulier dans les légumes-feuilles comme les épinards ou la laitue. Chez l’Homme, une partie des nitrates consommés peut être convertie en nitrites par les bactéries présentes dans la cavité buccale. ii) La présence non intentionnelle de nitrites dans les denrées alimentaires. Les nitrites peuvent notamment être présents dans les légumes mais à des teneurs généralement très inférieures aux nitrates. iii) L’utilisation de nitrites et de nitrates en tant qu’additifs dans les denrées alimentaires. Les nitrites de potassium et de sodium (E249, E250) et les nitrates de sodium et de potassium (E251, E252) sont couramment utilisés pour préserver la viande et d'autres produits périssables. Ils contribuent également à limiter la prolifération de microorganismes nuisibles, en particulier Clostridium botulinum, responsable du botulisme. Il s’agit d’additifs alimentaires autorisés dans l’Union européenne. A ce titre, ils ont fait l’objet de travaux scientifiques d’évaluation pour caractériser les risques liés à leur utilisation. Actuellement la réglementation européenne prévoit une teneur maximale d’incorporation de 150 mg/kg pour les produits de viande transformés, hors produits traditionnels. Pour les produits traditionnels dont la production est moindre en volume que les produits fabriqués par les industriels et qui contribuent donc moins à l’exposition des consommateurs, la réglementation prévoit une teneur de nitrites et nitrates résiduels pouvant aller jusqu’à 250 mg/kg. La teneur résiduelle varie selon différents facteurs liés au procédé de transformation (température de transformation, pH, présence d’acide ascorbique, etc.) et ne dépend pas uniquement de la teneur initialement incorporée. Les autorités danoises ont, pour leur part, souhaité maintenir un niveau d’emploi plus faible, à 60 mg/kg, qu’ils avaient fixé avant l’harmonisation européenne. L’association du fer-héminique avec les nitrites ajoutés a notamment été envisagée comme une explication du risque accru observé de développement de cancers du côlon ou du rectum lié à la consommation de certains produits carnés (données CIRC-INCa 2018)[2]. Le ferhéminique contenu dans la viande favoriserait la conversion des nitrites en nitrosamines, substances classées cancérogène probable (groupe 2A). Pour répondre à la demande des consommateurs, l’industrie a développé des solutions qu’elle présente comme alternatives à l’utilisation de sels nitrés (raccourcissement des DLC, bouillons de légumes, extraits de végétaux, etc.). En outre, des opérateurs s’engagent de manière plus globale à diminuer l’utilisation des additifs conformément aux objectifs définis par le programme national de l’alimentation et de la nutrition (PNAN). Dans le cadre de la réévaluation des additifs, l’Autorité européenne de sécurité des aliments (EFSA) a rendu des avis en juin 2017[3] et conclu, sur la base des éléments de preuve disponibles, que les niveaux de sécurité existants pour les nitrites et les nitrates ajoutés en tant qu’additifs à la viande et à d'autres aliments constituaient une protection adéquate pour les consommateurs. Plus précisément : ■ S’agissant des nitrates en tant qu’additif, et en ayant recours à des données dites réalistes (c’est-à-dire, les niveaux de concentration effectivement observés dans les aliments), les experts ont estimé que l'exposition des consommateurs aux nitrates utilisés comme additifs alimentaires était inférieure à 5% de l'exposition globale aux nitrates dans les aliments et ne dépassait pas la DJA ; ■ S’agissant des nitrites en tant qu’additif, les experts ont estimé que l'exposition se situait dans des limites sûres pour tous les groupes de population, à l'exception d'un léger dépassement chez les enfants dont le régime alimentaire est riche en aliments contenant ces additifs. De plus, le panel de l’EFSA soulignait, lorsque l’ensemble des sources d’expositions alimentaires (présence naturelle dans les aliments, contamination environnementale, utilisation en tant qu’additifs) étaient prises en compte : 1. pour les nitrates, des dépassements de la DJA pour l’ensemble des groupes d’âges (hypothèse d’exposition moyenne à haute) ; 2. pour les nitrites, des dépassements de la DJA pour l’ensemble des groupes d’âges sous l’hypothèse d’exposition haute, et pour des groupes d’âges spécifiques (nourrissons, jeunes enfants et enfants) sous l’hypothèse d’une exposition moyenne. L’EFSA a également émis des recommandations pour pallier certaines incertitudes. » En ce qui concerne les nitrates, des travaux ont été engagés à l’Anses afin de caractériser les expositions par voie alimentaire (notamment légumes et eau destinée à la consommation humaine) propres à la France dans le cadre de la saisine 2015-SA-0029. Ces travaux résultent d’une saisie de l’Anses par l’association Eaux et rivières de Bretagne (le 15/01/2015), par la Coordination rurale (le 19/01/2015) puis par la FNSEA (le 26/01/2015) sur les impacts sanitaires des nitrates présents dans l’alimentation et dans l’environnement. En effet, les habitudes alimentaires, de même que la présence de nitrates dans les aliments (légumes notamment) et l’eau, peuvent différer sensiblement des données européennes utilisées par l’EFSA. Cela est particulièrement vrai pour l’eau de consommation humaine distribuée dont les paramètres caractérisant sa qualité physico-chimique varient en fonction des ressources exploitées et des traitements mis en œuvre. Ces travaux avaient pour but d’apprécier, au plan national, la situation d’exposition de la population aux nitrates au regard des repères toxicologiques. Les résultats permettraient d’identifier les situations méritant attention, de façon à recommander des mesures, en particulier grâce à l’identification des aliments (y compris l’eau de boisson) les plus contributeurs à l’exposition aux nitrates en France. Ces travaux sont complétés par la présente expertise.
ano.nymous@ccsd.cnrs.fr.invalid (Marie-Louise Scippo) 13 Mar 2023
https://anses.hal.science/anses-04027039v1
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[anses-04066380] Avis de l'Anses relatif à l’étude de l’exposition aux nitrates par les eaux destinées à la consommation humaine (EDCH) des réseaux de distribution dans le cadre de la mise en demeure de la Commission européenne au regard de dépassements chroniques de la limite de qualité du paramètre « nitrates » dans les EDCH en France
La Directive 98/83/CE1, qui sera abrogée en 2023, et la Directive 2020/21842, relatives à la qualité des eaux destinées à la consommation humaine (EDCH) ont fixé, pour le paramètre « nitrates », une limite de qualité (LQ) à 50 mg L-1 dans les EDCH, limite qui est complétée par la vérification que la somme de la concentration en nitrates (en mg L-1) divisée par 50 et de celle en nitrites (en mg L-1) divisée par trois soit inférieure à un. L’arrêté du 11 janvier 2007 modifié, relatif aux limites et références de qualité des eaux brutes et des EDCH, transpose ces exigences en droit français. Cette limite de qualité est en accord avec les lignes directrices définies par l’Organisation mondiale de la santé (OMS) et est fondée sur des données épidémiologiques mettant en avant des cas de méthémoglobinémie chez le nourrisson (OMS 2017). La présente saisine intervient dans le contexte d’une mise en demeure de la France par la Commission européenne sur le non-respect de la Directive 98/83/CE pré-citée concernant le paramètre « nitrates ». La lettre de saisine précise que « cette mise en demeure concerne en particulier sept régions (Bourgogne Franche Comté, Centre Val de Loire, Grand Est, Hauts de France, Ile de France, Occitanie, Pays de la Loire) et 20 départements de France, où des dépassements chroniques de la limite de qualité du paramètre « nitrates » dans les EDCH ont été observés sur 213 unités de distribution (UDI) depuis plusieurs années voire dizaines d’années pour certaines [...]. Dans le cadre des échanges réguliers avec la Commission européenne, cette dernière a demandé aux autorités françaises d’évaluer l’impact sanitaire, sur les populations concernées, de ces expositions chroniques à des concentrations en nitrates dans l’eau dépassant la limite de qualité, en particulier pour les populations desservies par des unités de distribution pour lesquelles le calendrier de retour à la conformité n’est pas encore établi (soit 27 542 habitants alimentés par 116 UDI). » Par ailleurs, l’Anses a été saisie le 29 juin 2020 par la Direction générale de la santé (DGS), la Direction générale de l’alimentation (DGAL) et la Direction générale de la concurrence, de la consommation et de la répression des fraudes (DGCCRF), d’une demande d’avis relatif aux risques associés à la consommation de nitrites et nitrates (saisine 2020-SA-0106). Dans le cadre de cette saisine, l’Anses doit, entre autres, réévaluer la pertinence de la valeur toxicologique de référence de l’EFSA et al. (2017) et évaluer les risques sanitaires liés à l’exposition alimentaire aux nitrates, incluant la consommation d’EDCH. Ces travaux ont été finalisés début juillet 2022. Le périmètre de la présente saisine recoupe donc partiellement celui de la saisine 2020-SA-0106 relative aux risques associés à la consommation de nitrites et nitrates. [Saisine liée n° 2020-SA-0106]
ano.nymous@ccsd.cnrs.fr.invalid (Marie-Louise Scippo) 12 Apr 2023
https://anses.hal.science/anses-04066380v1
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[pasteur-01875323] Probing the influence of cell surface polysaccharides on nanodendrimer binding to Gram-negative and Gram-positive bacteria using single-nanoparticle force spectroscopy
The safe use and design of nanoparticles (NPs) ask for a comprehensive interpretation of their potentially adverse effects on (micro)organisms. In this respect, the prior assessment of the interactions experienced by NPs in the vicinity of - and in contact with - complex biological surfaces is mandatory. It requires the development of suitable techniques for deciphering the processes that govern nano-bio interactions when a single organism is exposed to an extremely low dose of NPs. Here, we used atomic force spectroscopy (AFM)-based force measurements to investigate at the nanoscale the interactions between carboxylate-terminated polyamidoamine (PAMAM) nanodendrimers (radius ca. 4.5 nm) and two bacteria with very distinct surface properties, Escherichia coli and Lactococcus lactis. The zwitterionic nanodendrimers exhibit a negative peripheral surface charge and/or a positive intraparticulate core depending on the solution pH and salt concentration. Following an original strategy according to which a single dendrimer NP is grafted at the very apex of the AFM tip, the density and localization of NP binding sites are probed at the surface of E. coli and L. lactis mutants expressing different cell surface structures (presence/absence of the O-antigen of the lipopolysaccharides (LPS) or of a polysaccharide pellicle). In line with electrokinetic analysis, AFM force measurements evidence that adhesion of NPs onto pellicle-decorated L. lactis is governed by their underlying electrostatic interactions as controlled by the pH-dependent charge of the peripheral and internal NP components, and the negatively-charged cell surface. In contrast, the presence of the O-antigen on E. coli systematically suppresses the adhesion of nanodendrimers onto cells, may the apparent NP surface charge be determined by the peripheral carboxylate groups or by the internal amine functions. Altogether, this work highlights the differentiated roles played by surface polysaccharides in mediating NP attachment to Gram-positive and Gram-negative bacteria. It further demonstrates that the assessment of NP bioadhesion features requires a critical analysis of the electrostatic contributions stemming from the various structures composing the stratified cell envelope, and those originating from the bulk and surface NP components. The joint use of electrokinetics and AFM provides a valuable option for rapidly addressing the binding propensity of NPs to microorganisms, as urgently needed in NP risk assessments.
ano.nymous@ccsd.cnrs.fr.invalid (Audrey Beaussart) 07 Feb 2022
https://pasteur.hal.science/pasteur-01875323v1
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[hal-04565273] New Approaches to Manage Infections in Transplant Recipients: Report From the 2023 GTI (Infection and Transplantation Group) Annual Meeting
This year’s GTI (“Groupe Transplantation and Infection”) annual meeting was held in Paris, France in February 2023. This meeting focused on new approaches to manage infectious complications in solid organ and stem cell transplant recipients. In this meeting report, we summarize the presentations and discussions from this annual meeting. Covered topics included new anti-infective agents and non-antibiotic approaches to manage infections due to multidrug-resistant Gram-negative bacteria, staphylococci, and fungal infections, as well as new approaches to manage symptomatic urinary tract infections and asymptomatic bacteriuria in kidney transplant recipients. Innovative approaches are needed to manage infectious complications in transplant recipients, who are at high risk of difficult-to-treat infections and side effects associated with the use of anti-infective agents.
ano.nymous@ccsd.cnrs.fr.invalid (Alexandra Serris) 17 Apr 2025
https://hal.inrae.fr/hal-04565273v1
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[hal-05062188] Corrigendum de « Actualisation des recommandations de prise en charge des pneumonies aiguës communautaires chez l’adulte par la Société de pathologie infectieuse de langue française (SPILF) et la Société de pneumologie de langue française (SPLF). Avec le soutien de la Société de réanimation de langue française, (SRLF), de la Société française de microbiologie (SFM), de la Société française de radiologie (SFR) et de la Société française de médecine d’urgence (SFMU) »
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ano.nymous@ccsd.cnrs.fr.invalid (A. Dinh) 09 May 2025
https://u-picardie.hal.science/hal-05062188v1
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[hal-04994246] Diet, fruit and vegetables and One Health: benefits for health, environment, society and the consumer—proceedings of the 9th edition of EGEA conference
Purpose To present the outcomes of the EGEA Conference on the state of knowledge regarding the contribution of diets rich in fruit and vegetables (FV) to human and planetary health, commonly included in the One Health concept. Methods The 9th edition of EGEA Conference (20-22 September 2023, Barcelona) provided a transversal and multidisciplinary perspective on the contribution of FV to One Health, in particular to the health of individuals, society and the planet. Nearly 150 international scientists and stakeholders discussed the current state of knowledge. These proceedings are based both on a literature review and the scientic studies presented by the speakers. Results Scientic evidence conrms the role of FV in preventing cardiovascular diseases and type 2 diabetes; more evidence is needed on the eects and mechanisms of FV in cancer prevention. FV production and consumption helps ensure territorial cohesion and provides a denser, nutrient-rich diet with less environmental impact (except water use) than other food groups, but use of synthetic pesticides in FV production remains a challenge that could be addressed with agro-ecological solutions. Various factors inuence consumer choice and behaviour towards FV consumption across the lifespan, with specic periods being more conducive to change. New research is emerging on the role of FV consumption in regulating gut microbiota and on both mental and brain health; the potential role of FV production and supply in tackling biodiversity loss and climate change; and better monitoring of FV consumption. Conclusion Sucient evidence conrms the contribution of diet rich in FV to One Health, with some emerging research on this topic. Concerted actions are required towards an increased consumption of FV and a more diversied and environmentally neutral FV production.
ano.nymous@ccsd.cnrs.fr.invalid (Nathalie Komati) 17 Mar 2025
https://hal.inrae.fr/hal-04994246v1
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[hal-04969936] Actualisation des recommandations de prise en charge des pneumonies aiguës communautaires chez l’adulte par la Société de pathologie infectieuse de langue française (SPILF) et la Société de pneumologie de langue française (SPLF). Avec le soutien de la Société de réanimation de langue française, (SRLF), de la Société française de microbiologie (SFM), de la Société française de radiologie (SFR) et de la Société française de médecine d’urgence (SFMU)
La durée de traitement antibiotique est réduite à trois jours si le patient est cliniquement stable à J3. L’hémisuccinate d’hydrocortisone est indiqué en cas de pneumonie aiguë communautaire (PAC) grave et doit être instauré rapidement. L’indication des PCR multiplex respiratoire doit être réservée à certaines situations précises. L’échographie pleuropulmonaire peut être utilisée en première intention pour le diagnostic radiologique de PAC. Le scanner thoracique est indiqué en cas de radiographie thoracique douteuse ou non interprétable.
ano.nymous@ccsd.cnrs.fr.invalid (A. Dinh) 27 Feb 2025
https://u-picardie.hal.science/hal-04969936v1
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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-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-04565259] Potential impact of real-time processing and rapid susceptibility testing of blood samples in Gram-negative bloodstream infections in intensive care patients
Introduction: Timely and appropriate therapy is critical in patients with Gram-negative bloodstream infections (GNBSI). Most bacteriology laboratories process blood specimen in the daytime, during laboratory operating hours, and use conventional culture for antimicrobial susceptibility testing (AST). We simulated the potential impact of real-time processing and rapid AST (7 hours) on early adaptation of the antibiotic regimen in intensive care unit (ICU) patients with GNBSI. Methods: All GNBSI episodes occurring in the ICUs of 2 hospitals in Paris were included. Data were collected. For each episode of bacteremia, we simulated the impact of three strategies: (1) Real-time processing coupled with conventional techniques (Gram stain and standard AST); (2) Standard processing coupled with rapid AST; and (3) Real-time processing coupled with rapid AST. Results: We included 109 episodes in 98 patients. Forty-two patients (48%) died during ICU stay. AST results led to a change of the antibiotic regimen in 66 (61%) episodes, mainly de-escalation (54/109, 55%). In standard care, median time from sample collection to definitive AST result was 65.9 hours (±26.7). The three strategies would have reduced time-to-result by 9.2 hours (±7.1), 30.8 hours (±19.7) and 40.0 hours (±20.6) respectively. Compared to standard care, strategies 1, 2 and 3 would have avoided 20, 69 and 90 patient-days of broad-spectrum antibiotics respectively. Conclusion: In addition to real-time processing of blood samples, rapid AST would be the most effective strategy to shorten time-to-result in critical patients with GNBSI.
ano.nymous@ccsd.cnrs.fr.invalid (S. Alviset) 01 May 2024
https://hal.inrae.fr/hal-04565259v1
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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-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-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-04144814] Frequency of surface bacterial contamination in family physicians’ offices
Objectives The environment is perceived as a potential source of healthcare-associated infections. While this infection source has been well studied in hospital settings, little data on the risk of contamination in general medical practice is available. We aimed to assess the frequency of environmental contamination in family practice (FP), and to describe pathogens isolated, at-risk surfaces, and factors associated with this contamination. Patients and methods We conducted a cross-sectional point prevalence study over six months in 51 FP offices. In each office, six environmental samples were collected after and before consultations on high-touch surfaces (stethoscope, examination table, physician's desktop, blood pressure cuff, medical equipment tray, computer keyboard and mouse). Results A total of 580 samples were obtained. All offices were contaminated at any time with at least 2.5 colony forming units. The median rate of examination room bio-cleaning was twice a week. For all equipment and surfaces, a lower bacterial load was found before consultations when the last cleaning had occurred less than 24 hours prior to testing. Conclusion High environmental contamination was observed in FP offices. Less than one practice in five used an effective cleaning agent; family physicians’ awareness of practice hygiene is an important step for prevention.
ano.nymous@ccsd.cnrs.fr.invalid (Pauline Huriez) 28 Jun 2023
https://hal.inrae.fr/hal-04144814v1
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[hal-03978239] A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates
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ano.nymous@ccsd.cnrs.fr.invalid (Stéphanie Pons) 08 Feb 2023
https://hal.univ-reims.fr/hal-03978239v1