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[hal-04438430] Long-term intake of Lactobacillus helveticus enhances bioavailability of omega-3 fatty acids in the mouse retina
Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several observational studies indicate that consumption of a diet with relatively high levels of n-3 PUFAs, such as those provided by fish oils, has a protective effect against the development of age-related macular degeneration. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lactobacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.
ano.nymous@ccsd.cnrs.fr.invalid (Pierre Lapaquette) 05 Feb 2024
https://hal.science/hal-04438430v1
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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-05427376] Estimating the Learning Capacity of Bacterial Metabolic Networks
Biocomputing has emerged as a promising field with the potential for energy-efficient computation, but standardized methods to evaluate living systems’ problem-solving capabilities remain underdeveloped. To address this gap, we focus on bacterial systems and their metabolic adaptation. Using an in-silico model of bacterial behavior in varying environments, we propose a new framework for transforming supervised machine learning (ML) problems into a format solvable by biological systems. We then evaluate the framework’s performance against other ML algorithms on standard classification and regression benchmarks. Experimental results show that bacterial metabolic networks often outperform linear methods and rival boosted trees, which are considered state-of-the-art for tabular data. A final ablation study suggests that the system’s computational capacity may stem from its biological components rather than the translation tools used for the learning problem.
ano.nymous@ccsd.cnrs.fr.invalid (Bastien Mollet) 20 Dec 2025
https://hal.science/hal-05427376v1
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[hal-04312782] Neural-like computation using bacterial metabolism to solve machine-learning problems
Throughout evolution, bacteria have acquired the ability to sense variations of the concentrations of nutrients in their growth medium. According to the medium composition, they adapt their metabolic behaviour by activating or repressing the appropriate metabolic pathways through a wide array of regulation mechanisms including transcriptional, translational or post-translational responses. Bacterial metabolism can therefore be compared to an algorithm taking as inputs the media composition and yielding as outputs metabolic fluxes describing its metabolic phenotype. Our work focuses on this perspective of the bacterial metabolism as an information processing unit. Our objective is to demonstrate that E. coli’s metabolism is capable of neural-like computation and to assess to what extend it can solve classical machine-learning problems (whether regression or classification). Our first step has been to generate an accurate model of E. coli’s metabolism, using the AMN (Artificial Metabolic Network), a metabolic hybrid model previously developed in our lab. This model has then been used to solve machinelearning problems of different complexities in order to assess the capacity of our metabolic model.
ano.nymous@ccsd.cnrs.fr.invalid (Paul Ahavi) 28 Nov 2023
https://hal.science/hal-04312782v1
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[hal-04287846] Evaluation of information processing capacity of bacterial metabolism through regression problem solving
Throughout evolution, bacteria have acquired the ability to sense variations of the concentrations of nutrients in their growth medium. According to the medium composition, they adapt their metabolic behaviour by activating or repressing the appropriate metabolic pathways through a wide array of regulation mechanisms including transcriptional, translational or post-translational responses. Bacterial metabolism can therefore be compared to an algorithm taking as inputs the media composition and yielding as outputs metabolic fluxes describing its metabolic phenotype. Our work focuses on this perspective of the bacterial metabolism as an information processing unit. Our objective is to demonstrate that E. coli's metabolism is capable of neural-like computation and to assess to what extend it can solve classical machine-learning problems (whether regression or classification). Our first step has been to generate an accurate model of E. coli's metabolism, using the AMN (Artificial Metabolic Network), a metabolic hybrid model previously developed in our lab. This model has then been used to solve machinelearning problems of different complexities in order to assess the capacity of our metabolic model.
ano.nymous@ccsd.cnrs.fr.invalid (Paul Ahavi) 15 Nov 2023
https://hal.science/hal-04287846v1
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[hal-05507083] Estimating the Learning Capacity of Bacterial Metabolic Networks
Biocomputing has emerged as a promising field with the potential for energy-efficient computation, but standardized methods to evaluate living systems' problem-solving capabilities remain underdeveloped. To address this gap, we focus on bacterial systems and their metabolic adaptation. Using an in-silico model of bacterial behavior in varying environments, we propose a new framework for transforming supervised machine learning (ML) problems into a format solvable by biological systems. We then evaluate the framework's performance against other ML algorithms on standard classification and regression benchmarks. Experimental results show that bacterial metabolic networks often outperform linear methods and rival boosted trees, which are considered state-of-the-art for tabular data. A final ablation study suggests that the system's computational capacity may stem from its biological components rather than the translation tools used for the learning problem.
ano.nymous@ccsd.cnrs.fr.invalid (Bastien Mollet) 12 Feb 2026
https://hal.science/hal-05507083v1
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[hal-04668230] A comprehensive, large-scale analysis of “terroir” cheese and milk microbiota reveals profiles strongly shaped by both geographical and human factors
An exhaustive analysis was performed on more than 2000 microbiotas from French Protected Designation of Origin (PDO) cheeses covering most cheese families produced throughout the world. Thanks to a complete and accurate set of associated metadata, we have carried out a deep analysis of the ecological drivers of microbial communities in milk and “terroir” cheeses. We show that bacterial and fungal microbiota from milk differed significantly across dairy species while sharing a core microbiome consisting of four microbial species. By contrast, no microbial species was detected in all ripened cheese samples. Our network analysis suggested that the cheese microbiota was organized into independent network modules. These network modules comprised mainly species with an overall relative abundance lower than 1%, showing that the most abundant species were not those with the most interactions. Species assemblages differed depending on human drivers, dairy species, and geographical area, thus demonstrating the contribution of regional know-how to shaping the cheese microbiota. Finally, an extensive analysis at the milk-to-cheese batch level showed that a high proportion of cheese taxa were derived from milk under the influence of the dairy species and PDO.
ano.nymous@ccsd.cnrs.fr.invalid (Francoise Irlinger) 19 Aug 2024
https://hal.science/hal-04668230v1
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[hal-03685819] The project INSECT4CITY: assessment of benefits and risks of insect-based bioconversion for recycling bio-waste from urban and peri-urban areas
In urban and peri-urban areas, where waste management is more than ever a major issue, insect farming may be an ecological way to recycle bio-waste in a circular bioeconomy approach. Indeed, someinsect species such as Hermetia illucens can grow on many types of organic substrates and can convert them into valuable byproducts(1). There may be a wide variety of insect bioconversion products since larvae are a natural source of micronutrients, amino acids and antimicrobial compounds. They are also rich in proteins which can be used for animal feed, in fats used for the production of biodiesel, in chitin used in various industries, and they produce a type of manure called frass that can be used as biofertilizer(2). However, besides its ecological and nutritional benefits, risks of insectbased bioconversion should be identified and monitored. Indeed, some chemical contaminants may be found in insect farming environment, in their feeding substrates or can be produced during processing methods(3). Moreover, microbiological contaminants may be found in the farming insect chain(4). Therefore, it is necessary to assess the impact of these contaminants on insect survival and to determine their fate in the insect. It is also important to assess the environmental, social and economic impact of insect-based bioconversion and to determine the consumer acceptability of these new processes and products
ano.nymous@ccsd.cnrs.fr.invalid (Erwan Engel) 02 Jun 2022
https://hal.inrae.fr/hal-03685819v1
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[hal-03135575] Benefits of Iterative Searches of Large Databases to Interpret Large Human Gut Metaproteomic Data Sets
The gut microbiota are increasingly considered as a main partner of human health. Metaproteomics enables us to move from the functional potential revealed by metagenomics to the functions actually operating in the microbiome. However, metaproteome deciphering remains challenging. In particular, confident interpretation of a myriad of MS/MS spectra can only be pursued with smart database searches. Here, we compare the interpretation of MS/MS data sets from 48 individual human gut microbiomes using three interrogation strategies of the dedicated Integrated nonredundant Gene Catalog (IGC 9.9 million genes from 1267 individual fecal samples) together with the Homo sapiens database: the classical single-step interrogation strategy and two iterative strategies (in either two or three steps) aimed at preselecting a reduced-sized, more targeted search space for the final peptide spectrum matching. Both iterative searches outperformed the single-step classical search in terms of the number of peptides and protein clusters identified and the depth of taxonomic and functional knowledge, and this was the most convincing with the three-step approach. However, iterative searches do not help in reducing variability of repeated analyses, which is inherent to the traditional data-dependent acquisition mode, but this variability did not affect the hierarchical relationship between replicates and all other samples.
ano.nymous@ccsd.cnrs.fr.invalid (Ariane Bassignani) 09 Feb 2021
https://hal.science/hal-03135575v1
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[hal-04942137] The gut microbiota posttranslationally modifies IgA1 in autoimmune glomerulonephritis
Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis. In the intestinal microbiota of patients with IgA nephropathy, there was increased relative abundance of mucin-degrading bacteria, including Akkermansia muciniphila . IgA1 was deglycosylated by A. muciniphila both in vitro and in the intestinal lumen of mice. This generated neo-epitopes that were recognized by autoreactive IgG from the sera of patients with IgA nephropathy. Mice expressing human IgA1 and the human Fc α receptor I (α1 KI -CD89 tg ) that underwent intestinal colonization by A. muciniphila developed an aggravated IgA nephropathy phenotype. After deglycosylation of IgA1 by A. muciniphila in the mouse gut lumen, IgA1 crossed the intestinal epithelium into the circulation by retrotranscytosis and became deposited in the glomeruli of mouse kidneys. Human α-defensins—a risk locus for IgA nephropathy—inhibited growth of A. muciniphila in vitro. A negative correlation observed between stool concentration of α-defensin 6 and quantity of A. muciniphila in the guts of control participants was lost in patients with IgA nephropathy. This study demonstrates that gut microbiota dysbiosis contributes to generation of auto-antigens in patients with IgA nephropathy and in a mouse model of this disease.
ano.nymous@ccsd.cnrs.fr.invalid (Patrick Gleeson) 12 Feb 2025
https://hal.science/hal-04942137v1
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[hal-04557632] The virtue of training: extending phage host spectra against vancomycin-resistant Enterococcus faecium strains using the Appelmans method
Phage therapy has (re)emerged as a serious possibility for combating multidrug-resistant bacterial infections, including those caused by vancomycin-resistant Enterococcus faecium strains. These opportunistic pathogens belong to a specific clonal complex 17, against which relatively few phages have been screened. We isolated a collection of 21 virulent phages growing on these vancomycin-resistant isolates. Each of these phages harbored a typical narrow plaquing host range, lysing at most 5 strains and covering together 10 strains of our panel of 14 clinical isolates. To enlarge the host spectrum of our phages, the Appelmans protocol was used. We mixed four out of our most complementary phages in a cocktail that we iteratively grew on eight naive strains from our panel, of which six were initially refractory to at least three of the combined phages. Fifteen successive passages permitted to significantly improve the lytic activity of the cocktail, from which phages with extended host ranges within the E. faecium species could be isolated. A single evolved phage able to kill up to 10 of the 14 initial E. faecium strains was obtained, and it barely infected nearby species. All evolved phages had acquired point mutations or a recombination event in the tail fiber genetic region, suggesting these genes might have driven phage evolution by contributing to their extended host spectra.
ano.nymous@ccsd.cnrs.fr.invalid (Julien Lossouarn) 24 May 2024
https://hal.inrae.fr/hal-04557632v1
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[hal-04396688] Correction to: Microbiome definition re-visited: old concepts and new challenges
An amendment to this paper has been published and can be accessed via the original article.
ano.nymous@ccsd.cnrs.fr.invalid (Gabriele Berg) 16 Jan 2024
https://hal.science/hal-04396688v1
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[hal-04099090] The need for an integrated multi‐OMICs approach in microbiome science in the food system
Microbiome science as an interdisciplinary research field has evolved rapidly over the past two decades, becoming a popular topic not only in the scientific community and among the general public, but also in the food industry due to the growing demand for microbiome-based technologies that provide added-value solutions. Microbiome research has expanded in the context of food systems, strongly driven by methodological advances in different -omics fields that leverage our understanding of microbial diversity and function. However, managing and integrating different complex -omics layers are still challenging. Within the Coordinated Support Action MicrobiomeSupport (), a project supported by the European Commission, the workshop "Metagenomics, Metaproteomics and Metabolomics: the need for data integration in microbiome research" gathered 70 participants from different microbiome research fields relevant to food systems, to discuss challenges in microbiome research and to promote a switch from microbiome-based descriptive studies to functional studies, elucidating the biology and interactive roles of microbiomes in food systems. A combination of technologies is proposed. This will reduce the biases resulting from each individual technology and result in a more comprehensive view of the biological system as a whole. Although combinations of different datasets are still rare, advanced bioinformatics tools and artificial intelligence approaches can contribute to understanding, prediction, and management of the microbiome, thereby providing the basis for the improvement of food quality and safety.
ano.nymous@ccsd.cnrs.fr.invalid (Ilario Ferrocino) 16 May 2023
https://hal.inrae.fr/hal-04099090v1
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[hal-01269697] Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.
The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features and healthy subjects (n = 26 in each group). Mastocytosis patients with digestive symptoms displayed significantly increased kynurenine level and IDO activity as compared to healthy controls and mastocytosis patients without digestive symptoms. This could be linked to mast cell-mediated digestive inflammation among patients with mastocytosis. This work is the first focusing on kynurenine pathway in a mast cell disease and could help to understand the pathogenesis of digestive features in mastocytosis as well as in other mast cell-mediated diseases.
ano.nymous@ccsd.cnrs.fr.invalid (Sophie Georgin-Lavialle) 23 Mar 2016
https://hal.science/hal-01269697v1
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[hal-03352408] A novel Enterococcus faecalis heme transport regulator (FhtR) is a heme sensor in the gastrointestinal tract
In this report, heme refers to iron protoporphyrin IX regardless of the iron redox state, whereas hemin refers to ferric iron protoporphyrin IX.
ano.nymous@ccsd.cnrs.fr.invalid (Vincent Saillant) 23 Sep 2021
https://hal.inrae.fr/hal-03352408v1
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[hal-04565315] Histamine elevation in familial Mediterranean fever : A study from the Juvenile Inflammatory Rheumatism cohort
The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes. Extensive purification of the clone’s supernatant demonstrates that the ABC-transporter allows for the efficient extracellular accumulation of three muropeptide precursor, with anti-inflammatory properties. They induce IL-10 secretion from human monocyte-derived dendritic cells and proved effective in reducing AIEC LF82 epithelial damage and IL-8 secretion in human intestinal resections. In addition, treatment with supernatants containing the muropeptide precursor reduces body weight loss and improves histological parameters in Dextran Sulfate Sodium (DSS)-treated mice. Until now, the source of peptidoglycan fragments was shown to come from the natural turnover of the peptidoglycan layer by endogenous peptidoglycan hydrolases. This is a report showing an ABC-transporter as a natural source of secreted muropeptide precursor and as an indirect player in epithelial barrier strengthening. The mechanism described here might represent an important component of the host immune homeostasis.
ano.nymous@ccsd.cnrs.fr.invalid (Nabiha Sbeih) 01 May 2024
https://hal.inrae.fr/hal-04565315v1
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[hal-05228170] In vitro assessment of cefepime adsorption in filters used during renal replacement therapy
Introduction: Renal replacement therapy efficiently eliminates cefepime. A published in vitro study concluded to minimal adsorption of cefepime in a polysulfone derived filter. We aimed at assessing cefepime adsorption in filters used in critically ill patients. Methods: Two filters were used, ST™150 and AV™1000. Adsorption was assessed in two modes, including diafiltration and filtration set to flow rates of from 2.5 to 1 L/h, respectively. Routes of elimination were assessed using NeckEpur ® method for 6-h session duration. Results: The mean initial concentration in the 5-L central compartment (CC) in the 10 sessions was 47.7 ± 2.9 mg/L. Using the diafiltration mode, the mean adsorption rates in the ST™150 and AV™1000 were 1.3 ± 2.3% and 19.7 ± 1.2% ( n = 3), respectively. Using the filtration mode at 1 L/h, the mean adsorption rates in the ST™150 and AV™1000 were 1.7% ( n = 2) and 18.5% ( n = 2), respectively. Conclusion: ST™150 filter sequestrated very limited quantities of cefepime. In the diafiltration and filtration modes, AV™1000 sequestered cefepime at about 19%. The adsorption rate seems independent of the flow rate. Further studies would be needed to assess, in particular, the clinical relevance of these results in adults as well as drug adsorption in the pediatric population.
ano.nymous@ccsd.cnrs.fr.invalid (Valentin Maulet) 28 Aug 2025
https://hal.science/hal-05228170v1
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[inserm-05502042] Impact of systematic screening for AmpC-hyperproducing Enterobacterales intestinal carriage in intensive care unit patients
Abstract Background Empirical antimicrobial therapy (EAT) is a challenge for community-acquired, hospital-acquired and ventilator-associated pneumonia, particularly in the context of the increasing occurrence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), including extended-spectrum beta-lactamase Enterobacterales (ESBL-E) and high-level expressed AmpC cephalosporinase-producing Enterobacterales (HLAC-E). To prevent the overuse of broad-spectrum antimicrobial therapies, such as carbapenems, we assessed the performance of screening for intestinal carriage of HLAC-E in addition to ESBL-E to predict 3GCR-E (ESBL-E and/or HLAC-E) presence or absence in respiratory samples in ICU, and to evaluate its potential impact on carbapenem prescription. Materials and methods This monocentric retrospective observational study was performed in a surgical ICU during a 4-year period (January 2013–December 2016). Patients were included if they had a positive culture on a respiratory sample and a previous intestinal carriage screening performed by rectal swabbing within 21 days. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for the screening for intestinal carriage of ESBL-E, HLAC-E and 3GCR-E (ESBL-E and/or HLAC-E) as predictor of their absence/presence in respiratory samples. Impact of HLAC-E and ESBL-E reporting on EAT was also studied. Results 765 respiratory samples, retrieved from 468 patients, were analyzed. ESBL-E prevalence was 23.8% in rectal swab and 4.4% in respiratory samples. HLAC-E prevalence was 9.0% in rectal swabs and 3.7% in respiratory samples. Overall, the 3GCR-E prevalence was 31.8% in rectal swabs and 7.7% in respiratory samples. NPVs were 98.8%, 98.0% and 96.6% for ESBL-E, HLAC-E and 3GCR-E, respectively. Over the study period, empirical antimicrobial therapy was initiated for 315 episodes of respiratory infections: 228/315 (72.4%) were associated with negative intestinal carriage screening for both HLAC-E and ESBL-E, of whom 28/228 (12.3%) were treated with carbapenems. Of 23/315 (7.3%) cases with screening for positive intestinal carriage with HLAC-E alone, 10/23 (43.5%) were treated with carbapenems. Conclusion Systematic screening and reporting of HLAC-E in addition to ESBL-E in intestinal carriage screening could help to predict the absence of 3GCR-E in respiratory samples of severe surgical ICU patients. This could improve the appropriateness of EAT in ICU patients with HAP and may prevent the overuse of carbapenems.
ano.nymous@ccsd.cnrs.fr.invalid (Elsa Manquat) 10 Feb 2026
https://inserm.hal.science/inserm-05502042v1
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[hal-05305119] Ecolabware: Carbon Footprint Comparator of Lab Single-Use Plasticware and Reusable Glassware
[...]
ano.nymous@ccsd.cnrs.fr.invalid (Marianne De Paepe) 09 Oct 2025
https://hal.inrae.fr/hal-05305119v1
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[hal-03172042] SARS-CoV-2 infection in nonhuman primates alters the composition and functional activity of the gut microbiota
The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota's composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instrumental in understanding and controling COVID 19. We used a nonhuman primate model (the macaque), that recapitulates mild COVID-19 symptoms, to analyze the effects of a SARS-CoV-2 infection on dynamic changes of the gut microbiota. 16S rRNA gene profiling and analysis of β diversity indicated significant changes in the composition of the gut microbiota with a peak at 10-13 days post-infection (dpi). Analysis of bacterial abundance correlation networks confirmed disruption of the bacterial community at 10-13 dpi. Some alterations in microbiota persisted after the resolution of the infection until day 26. Some changes in the relative bacterial taxon abundance associated with infectious parameters. Interestingly, the relative abundance of Acinetobacter (Proteobacteria) and some genera of the Ruminococcaceae family (Firmicutes) was positively correlated with the presence of SARS-CoV-2 in the upper respiratory tract. Targeted quantitative metabolomics indicated a drop in short-chain fatty acids (SCFAs) and changes in several bile acids and tryptophan metabolites in infected animals. The relative abundance of several taxa known to be SCFA producers (mostly from the Ruminococcaceae family) was negatively correlated with systemic inflammatory markers while the opposite correlation was seen with several members of the genus Streptococcus. Collectively, SARS-CoV-2 infection in a nonhuman primate is associated with changes in the gut microbiota's composition and functional activity.
ano.nymous@ccsd.cnrs.fr.invalid (Harry Sokol) 17 Mar 2021
https://hal.sorbonne-universite.fr/hal-03172042v1
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[anses-03922620] Évaluation des risques en appui des mesures de gestion de produits et sous-produits animaux dans la filière avicole, lors de suspicion et de confirmation des cas de botulisme
Le botulisme est une maladie neurologique humaine et animale provoquée par l’action de neurotoxines bactériennes (toxines botuliques) produites par des bactéries du genre Clostridium et qui se manifeste par des paralysies flasques pouvant aller jusqu’à la paralysie respiratoire et l’arrêt cardiaque. Il existe neuf types connus de toxines botuliques. Le botulisme animal en France concerne essentiellement les oiseaux (sauvages et d’élevage) et les bovins. Chez les oiseaux, les types toxiniques en cause sont C, D, mosaïques C/D et D/C et exceptionnellement le type E. Au niveau national, l’incidence est d’environ 25 foyers par an (volailles et avifaune confondues), avec cependant des variations annuelles parfois notables, par exemple en volailles en 2007 (121 foyers décelés) et 2008 (102 foyers). Bien qu’il s’agisse d’une maladie animale de première catégorie2, il n’y a pas à l’heure actuelle de mesures de police sanitaire établies par la réglementation, lors de la confirmation d’un foyer de botulisme animal, ce qui conduit à une gestion au cas par cas par les directions départementales de la protection des populations (DDPP) et la mission des urgences sanitaires (MUS) de la DGAL. Ces services peuvent s’appuyer sur deux documents émis par l’Afssa : le rapport sur le botulisme animal établi en 2002 et l’avis rendu en janvier 2009 sur un projet d’arrêté fixant des mesures techniques et administratives relatives à la lutte contre le botulisme aviaire. Les rapports et avis cités étant relativement anciens, la DGAL a saisi l’Anses via 4 saisines (saisines n°2019-SA-0112 à 2019-SA-0115), dont l’objet est une demande d’actualisation des connaissances et des évaluations de risque pour la santé humaine et/ou animale.
ano.nymous@ccsd.cnrs.fr.invalid (Philippe Fravalo) 09 May 2023
https://anses.hal.science/anses-03922620v1
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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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[inserm-03962400] Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales
Objectives: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020.Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to 3rd generation cephalosporins (3GC) (ESBL production or different levels of AmpC overexpression) (n=213) and carbapenem resistant Enterobacterales (CRE) (n=259) including 170 carbapenemase producers (CPE). Then, 1,632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by Etest® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison.Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80 % of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1,632 clinical isolates demonstrated 99 % of categorization agreement between MIC to C/T determined by Etest® compared to BMD (reference) and only 74% of essential agreement.Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers and ESBL-producing E. coli but is less active against ESBL-producing K. pneumoniae and CRE. Etest® led to an underestimation of the MICs in comparison to BMD.
ano.nymous@ccsd.cnrs.fr.invalid (Agnès Jousset) 30 Jan 2023
https://inserm.hal.science/inserm-03962400v1
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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
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[hal-05463801] Stenotrophomonas maltophilia – The most worrisome threat among unusual non-fermentative gram-negative bacilli from hospitalized patients: A prospective multicenter study
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ano.nymous@ccsd.cnrs.fr.invalid (Vincent Fihman) 17 Jan 2026
https://hal.science/hal-05463801v1
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[hal-04096890] Clinical relevance and antimicrobial susceptibility profile of the unknown human pathogen Corynebacterium aurimucosum
Introduction. Even though Corynebacterium aurimucosum has been described in 2002, this species has long been underestimated due to the unreliability of conventional identification methods and only a few cases of infections have been reported. Hypothesis/Gap Statement. Little is known about clinical significance and antimicrobial susceptibility profile of this uncommon species. Aim. To evaluate the clinical relevance of C. aurimucosum and its antimicrobial susceptibility profile. Methodology. All C. aurimucosum isolates, collected from 2010 to 2019 in 10 French university hospitals, were retrospectively included. Demographic, clinical and microbiological data were collected for all cases. Antimicrobial susceptibility testing was performed according to the 2019 EUCAST guidelines. Results. Fifty-seven clinical isolates of C. aurimucosum were collected in 57 patients (median age, 65.8 years; male/female sex ratio, 1.1), mostly from urine (28 %), blood culture (28 %) and bone/synovial fluid (19 %) samples. Of them, 14 cases of infection were confirmed, mainly bone and joint infections (50 %) followed by urinary tract infections (UTIs) (21 %), bacteremia (14 %), skin and soft-tissue infections (14 %). C. aurimucosum was recovered in pure culture in 36 % of cases (UTIs and bacteremia) while mixed cultures were observed for other infections. By testing 52 clinical isolates in vitro , this species appeared to be fully susceptible to linezolid and vancomycin while most isolates (>80 %) were susceptible to amoxicillin (MIC 90 , 2 µg ml −1 ), gentamicin, tetracycline and rifampicin. Both cefotaxime and ciprofloxacin seemed to have a limited activity (ca. 50 % of susceptible strains). The MIC distribution for ciprofloxacin showed a bimodal profile with a population of highly-resistant strains with MICs >2 µg ml −1 . Most isolates (>90 %) were categorized as resistant to penicillin G and clindamycin. Conclusion. C. aurimucosum should be considered as an actual opportunistic pathogen, and treatment with amoxicillin, vancomycin or linezolid should be preferred.
ano.nymous@ccsd.cnrs.fr.invalid (Charles Lefèvre) 14 May 2023
https://hal.science/hal-04096890v1
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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-03633007] Antimicrobial resistance in enterobacterales recovered from urinary tract infections in France
In the context of increasing antimicrobial resistance in Enterobacterales, the management of these UTIs has become challenging. We retrospectively assess the prevalence of antimicrobial resistance in Enterobacterales isolates recovered from urinary tract samples in France, between 1 September 2017, to 31 August 2018. Twenty-six French clinical laboratories provided the susceptibility of 134,162 Enterobacterales isolates to 17 antimicrobials. The most frequent species were $E.\ coli$ (72.0%), $Klebsiella\ pneumoniae$ (9.7%), $Proteus\ mirabilis$ (5.8%), and $Enterobacter\ cloacae$ complex (2.9%). The overall rate of ESBL-producing Enterobacterales was 6.7%, and ranged from 1.0% in $P.\ mirabilis$ to 19.5% in $K.\ pneumoniae$, and from 3.1% in outpatients to 13.6% in long-term care facilities. Overall, 4.1%, 9.3% and 10.5% of the isolates were resistant to cefoxitin, temocillin and pivmecillinam. Cotrimoxazole was the less active compound with 23.4% resistance. Conversely, 4.4%, 12.9%, and 14.3% of the strains were resistant to fosfomycin, nitrofurantoin, and ciprofloxacin. However, less than 1% of E. coli was resistant to fosfomycin and nitrofurantoin. We identified several trends in antibiotics resistances among Enterobacterales isolates recovered from the urinary tract samples in France. Carbapenem-sparing drugs, such as temocillin, mecillinam, fosfomycin, cefoxitin, and nitrofurantoin, remained highly active, including towards ESBL-E.
ano.nymous@ccsd.cnrs.fr.invalid (E. Farfour) 06 Apr 2022
https://hal.science/hal-03633007v1
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[hal-04981805] Update of guidelines for management of Community Acquired pneumonia in adults by the French Infectious Disease Society (SPILF) and the French-Speaking Society of Respiratory Diseases (SPLF)
Community-Acquired Pneumonia (CAP) of Presumed Bacterial Origin: Updated Management Guidelines Community-acquired pneumonia (CAP) of presumed bacterial origin is a common condition with varying severity, requiring either outpatient, hospital, or even critical care management. The French Infectious Diseases Society (SPILF) and the French Language Pulmonology Society (SPLF), in collaboration with the French Societies of Microbiology (SFM), Emergency Medicine (SFMU), Radiology (SFR), and Intensive Care Medicine (SRLF), along with representatives of general practice, have coordinated an update of the previous management guidelines, which dated back to 2010. From a therapeutic perspective, the updated recommendations define the choice of initial empiric antibiotic therapy, indications for combination therapy, the use of anti-Pseudomonas beta-lactams, antibiotic treatment duration, and the indications and modalities for prescribing systemic corticosteroids. On a biological level, indications for biomarkers and microbiological investigations have been refined. Regarding imaging, the role of different modalities in the diagnosis and follow-up of CAP has been reassessed, including chest X-ray, pleuropulmonary ultrasound, and thoracic CT scan.
ano.nymous@ccsd.cnrs.fr.invalid (Aurélien Dinh) 29 Sep 2025
https://u-picardie.hal.science/hal-04981805v1
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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-03505721] High prevalence of OXA-23 carbapenemase-producing Proteus mirabilis among amoxicillin-clavulanate resistant isolates in France
In this multicentric study performed in 12 French hospitals, we reported that 26.9% (14/52) of the amoxicillin-clavulanate-resistant Proteus mirabilis isolates produced the OXA-23 carbapenemase. We found that an inhibition zone diameter of <11 mm around the amoxicillin-clavulanate disc was an accurate screening cutoff to detect these OXA-23 producers. We confirmed by whole-genome sequencing that these OXA-23-producers all belonged to the same lineage that has been demonstrated to disseminate OXA-23 or OXA-58 in P. mirabilis.
ano.nymous@ccsd.cnrs.fr.invalid (Amélie Lombes) 13 Apr 2022
https://univ-fcomte.hal.science/hal-03505721v1
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[hal-04764180] Microbiological Profile of Instrumented Spinal Infections : 10-Year Study at a French Spine Center
Objective: The objective was to compare the microbiological characteristics and treatment of early and late surgical site infections (SSIs) in instrumented spinal surgery. Methods: Those patients admitted for SSIs in a single center between January 2010 and December 2022 were included. The subjects were divided into early (eSSIs) and late (lSSIs) SSIs, and demographic, microbiological, treatment, and follow-up data were collected. Results: Instrumented spinal surgery was performed in 2136 patients. Ninety-six cases of infections were identified (prevalence = 4.5%), with 47.9% eSSIs and 52.1% lSSIs. In 58.7% of the cases, the eSSIs were monomicrobial: Staphylococcus aureus (37%) and Enterobacterales (33.3%) were the main bacteria involved. In 66% of the cases, the lSSIs, were monomicrobial: Cutibacterium acnes (30.3%) and staphylococci were predominant. Enterobacterales were isolated in more than 70% of the polymicrobial samples in both the eSSIs and lSSIs. The treatment of the eSSIs mostly consisted of lavage-debridement surgery associated with antibiotic treatment, while the treatment of the lSSIs combined hardware removal or replacement and long-duration antibiotic treatment. A negative outcome was observed in 17.1% of the eSSIs and 5.7% of the lSSIs. Enterobacterales were associated with negative outcomes of eSSIs. Conclusions: Enterobacterales were found in most of the polymicrobial infections regardless of the time of infection onset. Further large studies should be conducted to precisely determine the management and prevention regarding the increasing Gram-negative bacteria SSIs.
ano.nymous@ccsd.cnrs.fr.invalid (Sophie Reissier) 03 Nov 2024
https://hal.inrae.fr/hal-04764180v1
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[hal-05228200] Value of molecular biology tests in community-acquired acute pneumonia
For patients hospitalized with community-acquired acute pneumonia (CAP), molecular tools (especially multiplex PCR syndromic panels) are associated with a significant improvement of microbiological diagnosis yield, compared with conventional methods. Two main families of tests are currently available: targeted viral PCR tests (influenza, SARS-CoV-2, RSV) performed on nasopharyngeal swabs and adapted to epidemic situations; and “upper respiratory tract” (nasopharyngeal) or “lower respiratory tract” (deep swabs) syndromic panels to detect a broad spectrum of viral and bacterial agents, sometimes including resistance genes. These tests are not recommended for routine use in CAP patients treated in ambulatory settings. In hospitalized CAP patients, their use must be guided by severity, epidemic context, and therapeutic implications. “Upper respiratory tract” panels can be useful when an atypical agent or a virus undetected by targeted PCR tests is suspected. “Lower respiratory tract” panels must only be used in case of severe forms or complex situations. Clinical trials showed real diagnostic value but variable clinical impact, which is often limited in the absence of an optimization strategy for the antibiotic therapy. Multiplex PCR syndromic panels represent a promising step forward in the management of patients hospitalized with CAP, but their clinical value still depends on several factors: type of panel and swab, quick results, presence of mobile teams of infectious diseases specialists, and capacity to correctly interpret results to guide treatment decisions.
ano.nymous@ccsd.cnrs.fr.invalid (V. Cattoir) 05 Nov 2025
https://hal.science/hal-05228200v1
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[hal-03216705] Temocillin susceptibility among Enterobacterales strains recovered from blood culture in France
Temocillin is used for several years in some European countries but, only since 2015 in France. We assessed the susceptibility of Enterobacterales strains isolated from blood culture 1 year before (2014) and 2 years after (2017) its use in France. 1,387 strains were included by 17 clinical laboratories located throughout France: 363 in 2014 and 1,024 in 2017. The rate of resistance to temocillin was 4.6% and 26.7% in 3rd generation cephalosporin (3GC) susceptible and resistant strains respectively. Cephalosporinase-overproducer (COPE) strains were significantly more resistant to temocillin (37.7%) than ESBL-producer (ESBL-PE) (23.5%) (P < 0.01). The rate of temocillin resistance was correlated to the number of inactive beta-lactams. The rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01). Temocillin remains highly active against Enterobacterales but the trend in resistance should be assessed over time.
ano.nymous@ccsd.cnrs.fr.invalid (Eric Farfour) 27 May 2021
https://univ-reims.hal.science/hal-03216705v1
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[hal-01834453] Live intramacrophagic Staphylococcus aureus as a potential cause of antibiotic therapy failure observations in an in vivo mouse model of prosthetic vascular material infections
Objectives: To evaluate the significant role played by biofilms during prosthetic vascular material infections (PVMIs).Methods: We developed an in vivo mouse model of Staphylococcus aureus PVMI allowing its direct observation by confocal microscopy to describe: (i) the structure of biofilms developed on Dacron® vascular material; (ii) the localization and effect of antibiotics on these biostructures; and (iii) the interaction between bacteria and host tissues and cells during PVMI.Results: In this model we demonstrated that the biofilm structures are correlated to the activity of antibiotics. Furthermore, live S. aureus bacteria were visualized inside the macrophages present at the biofilm sites, which is significant as antibiotics do not penetrate these immune cells.Conclusions: This intracellular situation may explain the limited effect of antibiotics and also why PVMIs can relapse after antibiotic therapy.
ano.nymous@ccsd.cnrs.fr.invalid (Rym Boudjemaa) 06 Sep 2018
https://univ-rennes.hal.science/hal-01834453v2
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[hal-01995119] Biofilms in food processing environments: challenges and opportunities
This review examines the impact of microbial communities colonizing food processing environments in the form of biofilms on food safety and food quality. The focus is both on biofilms formed by pathogenic and spoilage microorganisms and on those formed by harmless or beneficial microbes, which are of particular relevance in the processing of fermented foods. Information is presented on intraspecies variability in biofilm formation, interspecies relationships of cooperativism or competition within biofilms, the factors influencing biofilm ecology and architecture, and how these factors may influence removal. The effect on biofilm formation ability of particular food components and different environmental conditions that commonly prevail during food processing is discussed. Available tools for the in situ monitoring and characterization of wild microbial biofilms in food processing facilities are explored. Finally, research on novel agents or strategies for the control of biofilm formation or removal is summarized.
ano.nymous@ccsd.cnrs.fr.invalid (Avelino Alvarez-Ordóñez) 25 Jan 2019
https://hal.science/hal-01995119v1
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[hal-01204389] Molecular methods in food safety microbiology: Interpretation and implications of nucleic acid detection
Because of increasing demand for rapid results, molecular techniques are now applied for the detection of microorganisms in foodstuffs. However, interpretation problems can arise for the results generated by molecular methods in relation to the associated public health risk. Discrepancies between results obtained by molecular and conventional culture methods stem from the difference in target, namely nucleic acids instead of actively growing microorganisms. Nucleic acids constitute 5% to 15% of the dry weight of all living cells and are relatively stable, even after cell death, so they may be present in a food matrix after the foodborne microorganisms have been inactivated. Therefore, interpretation of the public health significance of positive results generated by nucleic acid detection methods warrants some additional consideration. This review discusses the stability of nucleic acids in general and highlights the persistence of microbial nucleic acids after diverse food-processing techniques based on data from the scientific literature. Considerable amounts of DNA and RNA (intact or fragmented) persist after inactivation of bacteria and viruses by most of the commonly applied treatments in the food industry. An overview of the existing adaptations for molecular assays to cope with these problems is provided, including large fragment amplification, flotation, (enzymatic) pretreatment, and various binding assays. Finally, the negligible risks of ingesting free microbial nucleic acids are discussed and this review ends with the future perspectives of molecular methods such as next-generation sequencing in diagnostic and source attribution food microbiology.
ano.nymous@ccsd.cnrs.fr.invalid (Siele Ceuppens) 23 Sep 2015
https://hal.science/hal-01204389v1
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[hal-02939442] Microbiome definition re-visited: old concepts and new challenges
The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term "microbiome." Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and future outlook. We propose a definition of microbiome based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes, and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice. Furthermore, microbiome standards are important for solving new challenges associated with anthropogenic-driven changes in the field of planetary health, for which the understanding of microbiomes might play a key role.
ano.nymous@ccsd.cnrs.fr.invalid (Gabriele Berg) 15 Sep 2020
https://hal.inrae.fr/hal-02939442v1
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[hal-04396666] Microbiome Interconnectedness throughout Environments with Major Consequences for Healthy People and a Healthy Planet
Microbiomes have highly important roles for ecosystem functioning and carry out key functions that support planetary health, including nutrient cycling, climate regulation, and water filtration. Microbiomes are also intimately associated with complex multicellular organisms such as humans, other animals, plants, and insects and perform crucial roles for the health of their hosts. Although we are starting to understand that microbiomes in different systems are interconnected, there is still a poor understanding of microbiome transfer and connectivity. In this review we show how microbiomes are connected within and transferred between different habitats and discuss the functional consequences of these connections. Microbiome transfer occurs between and within abiotic (e.g., air, soil, and water) and biotic environments, and can either be mediated through different vectors (e.g., insects or food) or direct interactions. Such transfer processes may also include the transmission of pathogens or antibiotic resistance genes. However, here, we highlight the fact that microbiome transmission can have positive effects on planetary and human health, where transmitted microorganisms potentially providing novel functions may be important for the adaptation of ecosystems.
ano.nymous@ccsd.cnrs.fr.invalid (Angela Sessitsch) 16 Jan 2024
https://hal.science/hal-04396666v1
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[hal-04707080] Improved gut microbiome recovery following drug therapy is linked to abundance and replication of probiotic strains
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ano.nymous@ccsd.cnrs.fr.invalid (Jamie Fitzgerald) 24 Sep 2024
https://hal.inrae.fr/hal-04707080v1
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[hal-05168198] Concepts and criteria defining emerging microbiome applications
In recent years, microbiomes and their potential applications for human, animal or plant health, food production and environmental management came into the spotlight of major national and international policies and strategies. This has been accompanied by substantial R&amp;D investments in both public and private sectors, with an increasing number of products entering the market. Despite widespread agreement on the potential of microbiomes and their uses across disciplines, stakeholders and countries, there is no consensus on what defines a microbiome application. This often results in non‐comprehensive communication or insufficient documentation making commercialisation and acceptance of the novel products challenging. To showcase the complexity of this issue we discuss two selected, well‐established applications and propose criteria defining a microbiome application and their conditions of use for clear communication, facilitating suitable regulatory frameworks and building trust among stakeholders.
ano.nymous@ccsd.cnrs.fr.invalid (Tanja Kostic) 17 Jul 2025
https://hal.inrae.fr/hal-05168198v1
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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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[hal-04619907] Recueil de projets d'expertise internationale à INRAE. Tome 2
Ce document dit "Recueil de projets d’expertise internationale" complète un premier volume édité en 2021 sur le même type d’activité (https://hal.inrae.fr/hal-04037409). Depuis la création en 2020 de la Direction Générale Déléguée à l’Expertise et l’Appui aux Politiques Publiques (DGDEAPP) il est souligné dans les échanges internes l’importance de mieux connaître, comprendre et "donner à voir" ce que recouvrent ces activités et les produits qui les caractérisent. L’Expertise-projet internationale (EPI) a été définie à travers une note de cadrage élaborée via un groupe d’experts référents. Cette note est accessible sur l’intranet de la DAPP. Au-delà de ce cadrage institutionnel, il semble important et opportun de partager les expériences concrètes, ainsi que la diversité des projets menés par les chercheurs sur cette activité. C’est le but de ce recueil que d’illustrer cette multitude de situations et d’expériences. Ainsi ce document rassemble une quarantaine de projets menés dans plus de 30 pays à travers le monde. On découvre à travers ce recueil un grand nombre d’organisations internationales commanditaires (bailleurs de l’expertise) allant de l’AFD, la FAO, le FIDA, La Banque Mondiale, l’Union Européenne (AEE, JRC), plusieurs agences onusiennes (OMS, PNUD, OMM, UNEP, GEF), l’OCDE, mais aussi des cabinets privés qui font appel à l’expertise scientifique des chercheurs de l’établissement. On y découvre également une grande diversité thématique qu’il est impossible de décrire sans en oublier mais qui vont de la sécurité sanitaire des aliments, des innovations institutionnelles pour une agriculture durable, des dispositifs d’alerte précoce pour prévenir les inondations (CREWS), la valorisation des eaux usées (REUSE), l’économie de la déforestation, les méthodes pour limiter l’impact de l’élevage (MRV), la robotique agricole, des méthodes et outils pour reconsidérer les inégalités, la pauvreté, les structures familiales etc. Si INRAE est aujourd’hui un acteur mondialement reconnu pour la réalisation de projets de recherche dimensionnant et de haut niveau, la montée en puissance des projets d’Expertise Internationale représente un nouveau vecteur de valorisation de ses savoir-faire en renforçant sa visibilité et sa notoriété.
ano.nymous@ccsd.cnrs.fr.invalid (Olga Chekhurska) 21 Jun 2024
https://hal.inrae.fr/hal-04619907v1
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[anses-04026651] Évaluation des risques relatifs aux mesures de décontamination et de gestion des sous-produits animaux lors des cas de botulisme bovin et aviaire
Le botulisme est une maladie neurologique humaine et animale, le plus souvent d’origine alimentaire, provoquée par l’action de neurotoxines bactériennes (toxines botuliques) produites par la bactérie Clostridium botulinum et qui se manifeste par une paralysie flasque pouvant aller jusqu’à la paralysie respiratoire et l’arrêt cardiaque. Neuf types toxiniques, répartis en une quarantaine de sous-types, sont actuellement connus. En France, le botulisme animal affecte essentiellement les oiseaux (sauvages et domestiques) et les bovins. Chez les volailles, on recense annuellement vingt à trente foyers, majoritairement dus aux types mosaïque C/D (élevages de poulets de chair et de dindes) suivi de D et mosaïque D/C (uniquement dans les élevages de dindes). Chez les bovins, l’incidence sur les 10 dernières années est en moyenne d’une dizaine de foyers par an et les épisodes de botulisme sont dus aux types mosaïque D/C (majoritaire), C, mosaïque C/D et rarement D. Les pertes en élevage liées à ces foyers et les interrogations sur leurs conséquences dans le domaine de la santé publique ont amené les pouvoirs publics à réglementer le botulisme animal en l’intégrant dans la liste des dangers sanitaires de première catégorie pour les espèces animales (arrêté du 29 juillet 2013). Aujourd’hui, cette maladie figure dans une liste des maladies animales réglementées d’intérêt national en application de l’article L. 221-1 du code rural et de la pêche maritime (arrêté du 03 mai 2022). Pour autant, aucune mesure de police sanitaire de portée générale n’a été édictée à ce jour pour gérer les foyers de botulisme animal, et chacun est géré au cas par cas par la direction départementale en charge de la protection des populations (DDPP) concernée, et par la Mission des Urgences Sanitaires (MUS) de la Direction Générale de l’Alimentation (DGAL). Jusqu’à présent, ces services se sont appuyés sur : un rapport sur le botulisme animal publié par l’Agence française de sécurité sanitaire des aliments (Afssa 2002) et un avis rendu en janvier 2009 sur un projet (par la suite abandonné) d’arrêté fixant des mesures techniques et administratives relatives à la lutte contre le botulisme aviaire (Afssa 2009b). Afin de pouvoir disposer de données actualisées et déterminer des mesures de gestion adaptées aux particularités du botulisme des type C, D et mosaïques C/D ou D/C, la DGAL a saisi l’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (Anses) à la fin du mois de juin 2019 via quatre saisines (saisines 2019-SA-0112 à 2019-SA-0115).
ano.nymous@ccsd.cnrs.fr.invalid (Jean Pierre Ganière) 13 Mar 2023
https://anses.hal.science/anses-04026651v1
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[hal-05495836] Ionized gas in NGC 4258: exploring the AGN–star formation connection
NGC 4258 is a prime target for studying feedback in low-luminosity active galactic nuclei (LLAGNs) due to its proximity and comprehensive multiwavelength coverage. Using new integral field spectroscopy (IFS) data from SITELLE at the Canada–France–Hawaii Telescope, we analysed the galaxy’s nebular emission lines. Our study focused on spatially resolved line ratios and Baldwin–Phillips–Terlevich diagrams, revealing that the ‘anomalous spiral arms’ exhibit intense interactions between the jet and interstellar medium (ISM) extending up to 6 kpc with velocity dispersions peak at 200–250 km s−1 in these regions, contrasting with star-forming areas showing lower values around of 30–50 km s−1. Analysis of covering fractions indicates heightened AGN ionization cones aligned with the radio jet, alongside evidence of shock quenching observed in the lower anomalous arc. Conversely, jet-induced compression may stimulate star formation in other areas. We derived a galaxy-wide star formation rate of $\sim 3\,{\rm M}_{\odot }\,\mathrm{yr}^{-1}$, decreasing to $0.3\,{\rm M}_{\odot }\,\mathrm{yr}^{-1}$ within the central 3.4 kpc$^2$. SITELLE’s broad field coverage elucidates the galaxy’s structural details, confirming that low-power jets significantly influence the host galaxy across parsec and kpc scales. The velocity dispersion map reveals asymmetric or double-peaked emission lines, tracing jet-disc interactions likely responsible for the formation of anomalous arm features. Small-scale ionizing clusters were detected in regions with disrupted gas flows, possibly formed through tidal interactions or shock compression. NGC 4258 thus presents a compelling case for studying LLAGN-driven feedback, illustrating how optical IFS combined with multiwavelength data clarifies the impact of outflows and shocks on nearby spiral galaxies, providing insights into how these processes shape star formation and ISM conditions.
ano.nymous@ccsd.cnrs.fr.invalid (D Fernández-Arenas) 20 Feb 2026
https://hal.science/hal-05495836v1
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[hal-05086448] Regorafenib plus avelumab in advanced gastroenteropancreatic neuroendocrine neoplasms: a phase 2 trial and correlative analysis
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors with limited treatment options. This phase 2 Bayesian study evaluated the combination of regorafenib, a multikinase inhibitor, and avelumab, a programmed death 1 (PD1) ligand 1 inhibitor, in advanced grade 2-grade 3 well-differentiated GEP neuroendocrine tumors or grade 3 GEP neuroendocrine carcinomas after progression on prior therapies. A total of 47 participants were enrolled and 42 were evaluable for efficacy. Participants received regorafenib (160 mg per day) and avelumab (10 mg kg-1 biweekly) in 28-day cycles. The primary endpoint, 6-month objective response rate per the response evaluation criteria in solid tumors version 1.1, was 18% (95% confidence interval (CI): 8-31%), with a median progression-free survival of 5.5 months (95% CI: 3.6-8). Durable responses were noted (16.6 months; 95% CI: 3.7-no response). Treatment-related adverse events were manageable, with fatigue, diarrhea and palmar-plantar erythrodysesthesia being most common. Exploratory biomarker analysis identified PD1 and indoleamine 2,3-dioxygenase 1 expression and activity as potential resistance markers. These findings highlight the clinical potential of regorafenib and avelumab in GEP-NENs, emphasizing the need for predictive biomarkers and validation in future randomized trials. Clinical Trial registration : NCT03475953.
ano.nymous@ccsd.cnrs.fr.invalid (Sophie Cousin) 27 May 2025
https://hal.science/hal-05086448v1
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[hal-02801289] Avis en réponse à la saisine du 7 novembre 2013, de Madame Marie-Christine Blandin, relative à l’article de Snell et al. (Food and Chemical Toxicology, 2012)
Le Haut Conseil des biotechnologies (HCB) a été saisi le 7 novembre 2013 par Madame la Sénatrice Marie-Christine Blandin, en vertu de l’article L531-3 du code de l’environnement, d’une demande d’avis relative à l’article de Snell et al., intitulé «Assessment of the health impact of GM plant diets in long-term and multigenerational animal feeding trials: A literature review», publié dans la revue Food and Chemical Toxicology (Snellet al.,2012). Pour répondre aux questions de la saisine, le Comité Scientifique (CS) du HCB a constitué un groupe de travail ad hoc. A la suite du compte-rendu de ce dernier, le CS du HCB a procédé à l’examen du projet de réponse le 25 février 2014 sous la présidence de Jean-Christophe Pagès.
ano.nymous@ccsd.cnrs.fr.invalid (Claude Bagnis) 02 Feb 2024
https://hal.inrae.fr/hal-02801289v1
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[hal-04497566] The role of hydrolysed diet in the management of chronic diarrhoea in dogs-is it always the first therapeutic step
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ano.nymous@ccsd.cnrs.fr.invalid (S Duvergé) 10 Mar 2024
https://hal.science/hal-04497566v1
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[hal-05244496] Interés de bacterias lácticas recombinantes en salud humana y animal
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ano.nymous@ccsd.cnrs.fr.invalid (Naima G Cortes-Perez) 08 Sep 2025
https://hal.inrae.fr/hal-05244496v1
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[anses-04026020] Avis relatif à la représentativité de l’échantillonnage pour la recherche d’histamine dans les poissons
L’histamine est l’une des principales causes de toxi-infections alimentaires liées à la consommation de poisson. L’intoxication histaminique est majoritairement liée à la consommation de poissons riches en histidine. Le comité du Codex Alimentarius sur l’hygiène alimentaire (CCFH) a adopté en 2018, dans le Code d’usages pour les poissons et les produits de la pêche, des orientations de type HACCP pour la maîtrise par les opérateurs de la formation de l’histamine (CXC 52-2003). En parallèle, des discussions sur les normes pour les produits (tels que le thon en conserve ou les blocs de filets de poissons) ont été initiées notamment concernant l’échantillonnage des lots. Dans ce contexte, l’Union européenne a proposé de reprendre le plan à trois classes du règlement européen (CE) n°2073/2005. D’autres pays (USA, Japon notamment) proposent un plan à deux classes avec un échantillonnage plus élevé. Ces divergences d’approches n’ont pas permis d’adopter les sections relatives aux méthodes d’analyse et à l’échantillonnage des produits. Des éléments techniques sont attendus dans le cadre de la reprise des discussions. En outre, l’appréciation de la conformité des lots est rendue délicate par l’hétérogénéité de la contamination des poissons, associée au fait que seule une petite partie des poissons prélevés peut être analysée. Dans ce contexte, la DGAL souhaite disposer d’orientations afin d’améliorer, d’une part les dispositions pour les contrôles officiels, et d’autre part l’appréciation de la pertinence des plans mis en place par les professionnels. Les deux questions adressées dans le courrier de la saisine sont les suivantes : « - L’approche présentée dans les travaux du Codex qui compare la puissance statistique des plans d’échantillonnage de l’histamine entre la position UE et celle des USA/Japon est-elle jugée pertinente ? Quels arguments pourraient présenter l’UE/la France pour défendre son approche lors de la reprise des échanges ? - Dans l’objectif d’établir des recommandations sur l’échantillonnage pour la recherche d’histamine lors des contrôles officiels d’une part, et pour juger de la pertinence des plans mis en place par les professionnels pour les autocontrôles d’autre part, quelles seraient les propositions d’orientations de l’Anses (partie du poisson utilisée comme échantillon, définition du lot, analyse systématique ou non de tous les lots, nombre maximal d’unités d’un échantillonnage composite/pooling, etc.) ? » La première question a fait l’objet d’une note d’appui scientifique et technique (AST) du 30 novembre 2021, la seconde question est l’objet de cet avis.
ano.nymous@ccsd.cnrs.fr.invalid (Philippe Fravalo) 13 Mar 2023
https://anses.hal.science/anses-04026020v1
