Publications

PUBLICATIONS

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HAL : Dernières publications

  • [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
  • [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
  • [hal-05425718] Optimized use of the FilmArray Meningitis/Encephalitis panel for early discontinuation of antibiotic therapy

    Introduction : La prise en charge des suspicions de méningite ou d’encéphalite repose sur une antibiothérapie empirique immédiate, souvent initiée avant la confirmation microbiologique. Dans ce contexte, le panel syndromique FilmArray® Méningite/Encéphalite (FAME) offre une réponse diagnostique rapide, mais son coût élevé soulève la question de son utilisation rationnelle. L’étude multicentrique FAMOuS (FilmArray® Meningitis/Encephalitis Optimization Study) visait à évaluer l’impact réel de FAME sur les décisions thérapeutiques précoces et à proposer un algorithme d’aide à la décision pour optimiser son emploi en routine hospitalière. Méthodes : Nous avons analysé rétrospectivement les données biologiques, les traitements instaurés avant et après obtention des résultats FAME, ainsi que les évolutions cliniques de 783 patients pris en charge dans six hôpitaux français sur une période de trois ans. Les indications, les résultats FAME, les modifications thérapeutiques et les examens complémentaires ont été comparés afin d’identifier les leviers d’optimisation. Résultats : Parmi les 783 panels réalisés, 80 % étaient négatifs, 7 % positifs pour une étiologie bactérienne et 13 % pour une origine virale. Aucun faux négatif bactérien n’a été observé. Les résultats positifs ont entraîné une modification thérapeutique dans 74 % des cas, contre 50 % pour les résultats négatifs. Les détections dans des prélèvements contenant <10 leucocytes ont concerné exclusivement des patients immunodéprimés ou des enfants de moins de 2 ans. Conclusion : L’étude FAMOuS a permis de concevoir un algorithme décisionnel basé sur les résultats du panel FAME et les profils cliniques des patients. Ce flowchart, appliqué en routine, pourrait éviter jusqu’à 33 % d’examens complémentaires non nécessaires et favoriser l’arrêt précoce de certaines antibiothérapies, sans compromettre la sécurité des patients.

    ano.nymous@ccsd.cnrs.fr.invalid (Nathan Nicolau-Guillaumet) 19 Dec 2025

    https://univ-reims.hal.science/hal-05425718v1
  • [anses-05426168] vvv2_align_SE, vvv2_align_PE / vvv2_display: Galaxy-based workflows and tool designed to perform, summarize and visualize variant calling and annotation in viral genome assemblies

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Alexandre Flageul) 19 Dec 2025

    https://anses.hal.science/anses-05426168v1
  • [hal-05423435] Bioproduction of 2-Phenylethanol by Yarrowia lipolytica on Sugar Beet Molasses as a Low-Cost Substrate

    2-phenylethanol (2-PE) is a valuable aromatic alcohol with diverse applications in cosmetics, food, beverages, and pharmaceutical industries. Currently, 2-PE is produced either through chemical synthesis or by extraction from plant materials. However, both conventional production methods have their own limitations. Therefore, there is a need for more eco-friendly and cost-effective approaches to produce natural 2-PE. Biotechnological routes, particularly microbial fermentations, hold promise for natural 2-PE production, especially when using low-cost substrates. In this study, 2-PE was produced by de novo synthesis via the shikimate pathway, using the yeast Yarrowia lipolytica in a medium composed of sugar beet molasses (SBM) and yeast extract (YE) as carbon and nitrogen sources, respectively. A genetically engineered strain was generated, in which the SUC2 gene was transformed, expressing the invertase enzyme, enabling Y. lipolytica to efficiently utilize SBM as a cost-effective substrate. A central composite design allowed for the optimization of the concentrations of the carbon and nitrogen sources, resulting in approximately 0.71 g(2-PE)/L(culture medium). The results obtained highlight the potential of utilizing SBM as a low-cost substrate for 2-PE production, advancing biotechnological approaches in fragrance synthesis.

    ano.nymous@ccsd.cnrs.fr.invalid (Sara Mitri) 18 Dec 2025

    https://hal.science/hal-05423435v1
  • [hal-05423360] Improving the Synthesis of Odd-Chain Fatty Acids in the Oleaginous Yeast Yarrowia lipolytica

    (1) Background: Odd-chain fatty acids (OCFAs) have garnered attention for their potential health benefits and unique roles in various biochemical pathways. Yarrowia lipolytica, a versatile yeast species, is increasingly studied for its capability to produce OCFAs under controlled genetic and environmental conditions. However, optimizing the synthesis of specific OCFAs, such as cis-9-heptadecenoic acid (C17:1), remains a challenge. (2) Methods: The gene coding for the Δ9 fatty acid desaturase, YlOLE1, and the gene coding the diacylglycerol O-acyltransferase 2, YlDGA2, were overexpressed in Y. lipolytica. With the engineered strain, the main goal was to fine-tune the production of OCFA-enriched lipids by optimizing the concentrations of sodium propionate and sodium acetate used as precursors for synthesizing odd- and even-chain fatty acids, respectively. (3) Results: In the strain overexpressing only YlDGA2, no significant changes in fatty acid composition or lipid content were observed compared to the control strain. However, in the strain overexpressing both genes, while no significant changes in lipid content were noted, a significant increase was observed in OCFA content. The optimal conditions for maximizing the cell density and the C17:1 content in lipids were found to be 2.23 g/L of sodium propionate and 17.48 g/L of sodium acetate. These conditions resulted in a cell density (optical density at 600 nm) of 19.5 ± 0.46 and a C17:1 content of 45.56% ± 1.29 in the culture medium after 168 h of fermentation. (4) Conclusions: By overexpressing the YlOLE1 gene and optimizing the concentrations of fatty acid precursors, it was possible to increase the content of OCFAs, mainly C17:1, in lipids synthesized by Y. lipolytica.

    ano.nymous@ccsd.cnrs.fr.invalid (Nour Tabaa Chalabi) 18 Dec 2025

    https://hal.science/hal-05423360v1
  • [hal-05423079] Sustainable 2-Phenylethanol Production: Co-Cultivation of Yarrowia lipolytica Strains in Mixed Agro-Industrial By-Products

    The bioproduction of 2-phenylethanol (2-PE), a high-value aromatic compound widely used in the fragrance, cosmetic, food and beverage, and pharmaceutical industries, through yeast fermentation offers a sustainable alternative to chemical synthesis and rose extraction. This study explores the fermentation of Yarrowia lipolytica strains using mixed agro-industrial by-products as substrates to produce 2-PE via de novo synthesis, without supplementation with the costly precursor L-phenylalanine. Y. lipolytica strains were genetically engineered to enhance flux through the shikimate pathway and enable the hydrolysis of a broader range of substrates. The culture media consisted solely of a mixture of agro-industrial by-products: sugar beet molasses (SBM), brewer’s spent grain (BSG) pressing extract, and chicory root (CR) pressing extract, serving as the primary carbon and nitrogen sources without the addition of nutrients, minerals, synthetic, complex ingredients, or costly additives. The co-culture approach enhanced substrate utilization, leading to an increase in 2-PE titers, reaching approximately 2.5 g/L 2-PE production after 240 h of fermentation. This study demonstrates the feasibility of integrating co-culture fermentation and agro-industrial waste valorization for sustainable 2-PE production, offering a scalable bioprocess for industrial applications.

    ano.nymous@ccsd.cnrs.fr.invalid (Sara Mitri) 18 Dec 2025

    https://hal.science/hal-05423079v1
  • [hal-05333962] BioRGroup dataset: R-group expansion of ChEBI molecules referenced in the Rhea database

    Abstract The application of artificial intelligence in cheminformatics highlights the necessity of comprehensive datasets that fully utilize all available chemical information. While generalist databases such as PubChem provide extensive compound coverage, specialised resources such as Rhea, which relies on the ChEBI ontology, are critical for the study of enzyme-catalysed reactions. A notable challenge arises from the presence of generic structures in ChEBI molecules, which incorporate R-groups as placeholders for various molecular fragments. This creates difficulties for their use in computational pipelines, such as those applied in retro-biosynthesis and biocatalysis. To address this issue, a curated dataset is presented that resolves R-group-containing ChEBI entries into fully defined molecular instances. The pipeline extracts generic molecules from Rhea, identifies compatible substitutions using PubChem and RDKit, and applies tailored filters to generate chemically valid enumerations. The dataset, BioRGroup, is delivered in a standard file format, thereby enabling the systematic integration of previously under-utilised generic structures into computational workflows, enhancing the scope and granularity of chemical data analysis.

    ano.nymous@ccsd.cnrs.fr.invalid (Guillaume Gricourt) 27 Oct 2025

    https://hal.science/hal-05333962v1
  • [hal-04484107] Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation

    The anaerobic bacterium Fusobacterium nucleatum is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms underlying the promotion of intestinal tumor formation by F. nucleatum have only been partially uncovered. Here, we showed that F. nucleatum releases a metabolite into the microenvironment that strongly activates NF-κB in intestinal epithelial cells via the ALPK1/TIFA/TRAF6 pathway. Furthermore, we showed that the released molecule had the biological characteristics of ADPheptose. We observed that F. nucleatum induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, BIRC3 and TNFAIP3. Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity in vitro. Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in Fusobacterium induced-CRC pathogenesis, and identify the role of ADP-H in this process.

    ano.nymous@ccsd.cnrs.fr.invalid (Camille Martin-Gallausiaux) 29 Feb 2024

    https://hal.inrae.fr/hal-04484107v1
  • [hal-04092647] Use of genetically modified lactic acid bacteria and bifidobacteria as live delivery vectors for human and animal health

    There is now strong evidence to support the interest in using lactic acid bacteria (LAB)in particular, strains of lactococci and lactobacilli, as well as bifidobacteria, for the development of new live vectors for human and animal health purposes. LAB are Gram-positive bacteria that have been used for millennia in the production of fermented foods. In addition, numerous studies have shown that genetically modified LAB and bifodobacteria can induce a systemic and mucosal immune response against certain antigens when administered mucosally. They are therefore good candidates for the development of new mucosal delivery strategies and are attractive alternatives to vaccines based on attenuated pathogenic bacteria whose use presents health risks. This article reviews the most recent research and advances in the use of LAB and bifidobacteria as live delivery vectors for human and animal health.

    ano.nymous@ccsd.cnrs.fr.invalid (Romina Levit) 09 May 2023

    https://hal.inrae.fr/hal-04092647v1
  • [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
  • [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
  • [hal-04316558] Infective anoproctitis in men having sex with men: Don’t forget Mycoplasma genitalium

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    ano.nymous@ccsd.cnrs.fr.invalid (V. Berti) 30 Nov 2023

    https://hal.science/hal-04316558v1
  • [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
  • [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
  • [hal-04144819] Epidemiology and clinical characteristics of Klebsiella spp. meningitis in France

    Objectives: To describe the epidemiology of Klebsiella spp. meningitis in France with respect to clinical and bacteriological data. Methods: We performed a four-year multicenter, retrospective, observational study. The primary objective was to provide a clinical description of patients with Klebsiella spp. meningitis. Secondary objectives were to compare community-acquired meningitis and healthcare-associated meningitis and to analyze factors associated with mortality. Results: We enrolled 131 patients with Klebsiella spp. meningitis. Eighty-two (62.6%) infections were reported following neurosurgery. Twenty-eight strains (21.4%) were resistant to third-generation cephalosporins (3GC). The median [IQR] cellularity was 980/mm3 [116-5550], the median protein level was 5.67 [1.62-9] g/L and the median CSF glucose level was 2.5 [0-3.4] mmol/L. The in-hospital mortality rate was 23.6%. Community-acquired meningitis isolates were more frequently susceptible to 3GC than isolates from healthcare-associated meningitis (89.2% versus 72%; P=0.04). Comorbidities reported for patients with community-acquired meningitis were mainly diabetes mellitus and liver cirrhosis. In multivariate analysis, focal neurological disorder at the time of diagnosis was the only factor associated with in-hospital mortality (P=0.01). Conclusions: Purulent meningitis caused by Klebsiella spp. needs to be considered in patients with community-acquired meningitis and preexisting conditions, as well as in case of meningitis following neurosurgical procedures.

    ano.nymous@ccsd.cnrs.fr.invalid (Benoît Pilmis) 28 Jun 2023

    https://hal.inrae.fr/hal-04144819v1
  • [hal-03983231] Evolution of anti-SARS-CoV-2 immune response in a cohort of French healthcare workers followed for 7 months

    Objectives : We aimed to understand the immune response among healthcare workers (HCWs) following SARS-CoV-2 infection, and to determine the infection prevalence during the first wave of the pandemic among workers in our hospital. Methods : Determination of the serological status against SARS-CoV-2 (nucleocapsid) was offered to all HCWs. All HCWs with positive SARS-CoV-2 serology were proposed to be included in a longitudinal medical and serological follow-up (anti-spike) for 7 months. Results : We included 3062 HCWs; 256 (8.4%) were positive for anti-SARS-CoV-2 nucleocapsid IgG. Among them, early decrease in the anti-nucleocapsid antibody index was observed between the first (S1) and second (S2) serology samplings in 208 HCWs (84.2%). The initial anti-nucleocapsid IgG index seemed to be related to the HCWs' age. Seventy-four HCWs were included in the 7-month cohort study. Among them, 69 (90.5%) had detectable anti-spike IgG after 7 months and 24 (32.4%) reported persistent symptoms consistent with post-acute COVID-19 syndrome diagnosis. Conclusion : The prevalence of serological positivity among HCWs was 6.7%. Infection should be followed by vaccination because of antibody decrease.

    ano.nymous@ccsd.cnrs.fr.invalid (Benoît Pilmis) 10 Feb 2023

    https://hal.science/hal-03983231v1
  • [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
  • [hal-04144813] Is the second dose of vaccination useful in previously SARS-CoV-2-infected healthcare workers?

    Vaccines are the most important public health measure to protect people from COVID-19 worldwide. In addition, healthcare workers account for a large number of infected people. Protecting this population from COVID-19 seems crucial to preserve healthcare systems. In a context of few doses available, serological assays could be useful to decide whether one or two doses are needed. Our results show that a first dose of BNT162b2 mRNA vaccine seems to act as a boost after SARS-CoV-2 infection in healthcare workers with a previous SARS-CoV-2 infection; a second dose might therefore not be required.

    ano.nymous@ccsd.cnrs.fr.invalid (G. Pean de Ponfilly) 28 Jun 2023

    https://hal.inrae.fr/hal-04144813v1
  • [hal-02712082] Ultradian variations in sensitivity of rat aorta rings to noradrenaline

    The in vitro sensitivity of the rat aorta to the vasoconstrictor effect of noradrenaline was found to vary according to the time the animals were killed, with a minimum at 10:00 h and a maximum at 16:00 h. This ultradian rhythm was not influenced by the presence of the endothelium but was modified by some, as yet unidentified, circulating factor(s). The results also strongly suggested an ultradian rhythm of in vitro sensitivity to the β-adrenoceptor agonists, salbutamol and isoprenaline. This rhythm appears to be opposite to that for the sensitivity of aortic α-adrenoceptors to stimulation. In conclusion, our results demonstrate that the regulation of aortic tone follows an ultradian rhythm.

    ano.nymous@ccsd.cnrs.fr.invalid (Michel Gohar) 01 Jun 2020

    https://hal.inrae.fr/hal-02712082v1
  • [hal-04303436] Purification of Natural Pigments Violacein and Deoxyviolacein Produced by Fermentation Using Yarrowia lipolytica

    Violacein and deoxyviolacein are bis-indole pigments synthesized by a number of microorganisms. The present study describes the biosynthesis of a mixture of violacein and deoxyviolacein using a genetically modified Y. lipolytica strain as a production chassis, the subsequent extraction of the intracellular pigments, and ultimately their purification using column chromatography. The results show that the optimal separation between the pigments occurs using an ethyl acetate/cyclohexane mixture with different ratios, first 65:35 until both pigments were clearly visible and distinguishable, then 40:60 to create a noticeable separation between them and recover the deoxyviolacein, and finally 80:20, which allows the recovery of the violacein. The purified pigments were then analyzed by thin-layer chromatography and nuclear magnetic resonance.

    ano.nymous@ccsd.cnrs.fr.invalid (Georgio Nemer) 02 Feb 2024

    https://hal.science/hal-04303436v1
  • [hal-05268445] Th1 and Th2 cells are required for both eosinophil- and neutrophil-associated airway inflammatory responses in mice

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    ano.nymous@ccsd.cnrs.fr.invalid (Romy Dejean de la Batie) 19 Sep 2025

    https://hal.inrae.fr/hal-05268445v1
  • [hal-04841808] Méthodes d’évaluation des risques sanitaires et environnementaux et des enjeux socio-économiques associés aux plantes obtenues au moyen de certaines nouvelles techniques génomiques (NTG)

    Depuis le 1er janvier 2022, conformément à l’ordonnance n° 2021-1325 du 13 octobre 2021 et au décret n° 2021-1905 du 30 décembre 2021, l’Anses reprend les missions du Haut conseil des biotechnologies (HCB) concernant l’évaluation des risques pour l’environnement de l’ensemble des utilisations de biotechnologies en milieu ouvert, et les impacts socioéconomiques. L’Anses a été saisie dans le cadre de ces nouvelles missions par la Direction générale de la prévention des risques (DGPR) et la Direction générale de l’alimentation (DGAl) sur l’utilisation des nouvelle techniques génomiques (NTG) sur les végétaux. Les autres instances ayant repris les missions du HCB, à savoir le Conseil économique, social et environnemental (CESE) et le Comité consultatif national d’éthique (CCNE), ont également été sollicité sur cette question sur les périmètres correspondant respectivement aux questions sociétales et éthiques. Par ailleurs, il convient de noter que de nombreux acteurs institutionnels publics, organisations professionnelles et syndicales ont également produit des rapports sur les NTG. Le rapport d’expertise collective est réalisé dans le périmètre des missions de l’Anses sur les biotechnologies, incluant l’évaluation des risques sanitaires et environnementaux et les impacts socio-économiques. Il vise à éclairer les demandeurs sur ce périmètre qui couvre seulement une partie des enjeux liés à l’utilisation des NTG dans le domaine de la sélection végétale. Les questions instruites dans ce rapport sont donc limitées à ce périmètre et les conclusions devront être prises en compte uniquement dans ce cadre et mises en perspective avec les avis des autres instances sollicitées. Il convient de noter que cette expertise a été engagée avant la proposition de règlement de la Commission du 5 juillet 20231. Suite à sa publication, l’Anses a décidé de s’autosaisir afin de mener une analyse des critères définissant les plantes NTG de catégorie 1, considérées comme équivalentes aux plantes conventionnelles, exposés dans l’annexe 1 et justifiés par une note technique diffusée par la Commission européenne en octobre (Anses 2023). Cette analyse a été réalisée en parallèle et ses conclusions n’ont donc pas été prises en compte dans le présent travail d’expertise, réalisé dans le cadre du périmètre défini précédemment, qui ne fait pas la distinction entre les plantes NTG de catégorie 1 et 2.

    ano.nymous@ccsd.cnrs.fr.invalid (Michel Gautier) 16 Dec 2024

    https://cnrs.hal.science/hal-04841808v1
  • [hal-03031236] Fecal microbiota transplantation to maintain remission in Crohn’s disease: a pilot randomized controlled study

    Background: The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileocolonic CD. Method: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6). Results: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified. Conclusion: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797).

    ano.nymous@ccsd.cnrs.fr.invalid (Harry Sokol) 30 Nov 2020

    https://hal.sorbonne-universite.fr/hal-03031236v1
  • [anses-04171242] Évaluation des impacts sur la santé publique de la dynamique des populations de renards

    Le Renard roux (Vulpes vulpes) est une espèce de la faune sauvage. En tant que gibier, il peut être chassé par différents moyens. Il est de plus susceptible d’être inscrit, dans certains territoires, comme espèce susceptible d’occasionner des dégâts (ESOD) par arrêté ministériel triennal pris en application de l’article R.427-6 du Code de l’environnement. Nonobstant les restrictions sur les périodes de chasse, les animaux classés ESOD peuvent être éliminés toute l’année. En 2019 et pour trois ans, suite à des consultations départementales et un arbitrage ministériel, le renard a été classé ESOD dans 90 départements français. La décision de classement doit être motivée. Plusieurs arguments sont avancés pour ce classement : pertes dans les élevages avicoles ou de gibier, raisons sanitaires (par ex. : échinococcose alvéolaire, gale sarcoptique). Inversement, des bénéfices liés à la présence des renards sont également avancés, tels que la prédation de rongeurs (campagnols notamment), porteurs d’agents zoonotiques, la réduction d’utilisation de raticides, etc. ... Dans un rapport et avis sur le rôle épidémiologique du renard dans le système multihôtes de la tuberculose bovine (Anses 2021), l’Anses notait que l’importance des nuisances attribuées aux renards faisait l’objet de controverses et de polémiques en France. La présente saisine s’inscrit ainsi dans un contexte sociétal sensible impliquant notamment les associations de protection de la nature et les chasseurs ou les éleveurs. Les réponses à cette saisine visent à clarifier le rôle du renard dans l’épidémiologie de certaines zoonoses pour lesquelles il est présenté comme premier responsable de la transmission à l’humain, ce qui motive certains acteurs à proposer son classement en tant qu’ESOD.

    ano.nymous@ccsd.cnrs.fr.invalid (Emmanuelle Gilot-Fromont) 04 Mar 2025

    https://anses.hal.science/anses-04171242v1
  • [hal-05124696] Impacts sur la santé publique de la dynamique des populations de renards

    The Red Fox (Vulpes vulpes) can be hunted as a game species. It may also be listed as a “species likely to cause damage” (ESOD – the acronym in French), for public health reasons among others. Conversely, benefits linked to the presence of foxes are also put forward, such as the predation of rodents carrying zoonotic agents. In this context, ANSES was asked to: (1) list the zoonoses present in France for which foxes play an epidemiological role, (2) identify other public health impacts associated with changes in fox populations, (3) explain the relative importance of the effects of changes in fox populations for humans and/or the environment, (4) analyse the feasibility of a cost‐benefit analysis (CBA) of the prevention and impacts associated with these zoonoses. In France, the fox is a source of zoonotic pathogens, with a major role for Echinococcus multilocularis, a parasite for which the fox is the main source of environmental contamination. However, reducing fox populations does not reduce the risk of transmission of E. multilocularis to humans or domestic animals, and may even have the opposite effect to the one intended. The main levers for action are those relating to exposure to environmental contamination. The fox is part of complex trophic networks, in which its specific role in regulating prey populations is impossible to determine because (i) several predators share the same prey, with a variable role for the fox among the predators, (ii) the dynamics of prey populations is also conditioned by factors other than predation. The relationship between the abundance of rodents and the risk of disease for humans has not been demonstrated either, due to the complexity of the trophic and epidemiological networks, their highly probable variability from one ecosystem to another, and the multiplicity of hosts. As a result, the data currently available does not allow any conclusions to be drawn about the epidemiological role of the fox as a predator of rodents hosting zoonotic agents. Finally, there is no public health justification for culling foxes, particularly for ESOD classification, except in the very specific and localised context of the fight against bovine tuberculosis, for which the selective culling of foxes in and around the livestock buildings of a domestic outbreak has been proposed. In addition, the expertise concluded to the feasibility of a CBA targeted at assessing the burden of alveolar echinococcosis and measures to prevent its transmission. The feasibility study shows the partial nature of a CBA targeting zoonoses, without taking into account other roles played by the fox in the ecosystem.

    ano.nymous@ccsd.cnrs.fr.invalid (Emmanuelle Gilot-Fromont) 18 Jul 2025

    https://hal.science/hal-05124696v1
  • [pasteur-05420000] The influence of environment on bacterial co-abundance in the gut microbiomes of healthy human individuals

    The gut microbiome is a complex ecosystem characterized not only by its marginal taxonomic composition but also by its emergent properties. Bacteria develop local interactions to form coherent functional communities, whose effects on health and diseases cannot be predicted from the behavior of individual members. Understanding the factors underlying variability in these communities may therefore provide critical insights on the biological links between the gut microbiome and human phenotypes. Here, we examined the effect of a range of host factors, including demographics, medical history, and dietary habits, on these communities in 938 healthy individuals using MANOCCA, a covariance-based approach developed to address existing limitations. Increased age and smoking were associated with a significant overall decrease in co-abundance, and conversely a higher body mass index was associated with increased co-abundance. At the taxon level, a core of 200 genera were systematically impacted in their co-abundance with other taxa, suggesting a central role in structuring the network. Finally, we demonstrate that our approach offers a powerful framework for prediction purposes, with taxa co-abundance being able to predict the age of participants with an accuracy three-fold higher than a model based on abundance only.

    ano.nymous@ccsd.cnrs.fr.invalid (Christophe Boetto) 17 Dec 2025

    https://pasteur.hal.science/pasteur-05420000v1
  • [hal-02153623] Glyphosate and glyphosate-based herbicide exposure during the peripartum period affects maternal brain plasticity, maternal behaviour and microbiome

    Glyphosate is found in a large array of non‐selective herbicides such as Roundup® (Monsanto, Creve Coeur, MO, USA) and is by far the most widely used herbicide. Recent work in rodent models suggests that glyphosate‐based herbicides during development can affect neuronal communication and result in altered behaviours, albeit through undefined mechanisms of action. To our knowledge, no study has investigated the effects glyphosate or its formulation in herbicide on maternal behaviour and physiology. In the present study, relatively low doses of glyphosate (5 mg kg‐1 d‐1), Roundup® (5 mg kg‐1 d‐1 glyphosate equivalent), or vehicle were administered by ingestion to Sprague‐Dawley rats from gestational day (GD) 10 to postpartum day (PD)22. The treatments significantly altered licking behaviour toward pups between PD2 and PD6. We also show in the dams at PD22 that Roundup exposure affected the maturation of doublecortin‐immunoreactive new neurones in the dorsal dentate gyrus of the hippocampus of the mother. In addition, the expression of synaptophysin was up‐regulated by glyphosate in the dorsal and ventral dentate gyrus and CA3 regions of the hippocampus, and down‐regulated in the cingulate gyrus. Although a direct effect of glyphosate alone or its formulation on the central nervous system is currently not clear, we show that gut microbiota is significantly altered by the exposure to the pesticides, with significant alteration of the phyla Bacteroidetes and Firmicutes. This is the first study to provide evidence that glyphosate alone or in formulation (Roundup) differentially affects maternal behaviour and modulates neuroplasticity and gut microbiota in the mother.

    ano.nymous@ccsd.cnrs.fr.invalid (Julie Dechartres) 01 Jul 2019

    https://univ-rennes.hal.science/hal-02153623v1
  • [hal-05422050] A scoping review of the health effects of fermented foods in specific human populations and their potential role in precision nutrition: current knowledge and gaps

    Background Diets and specific foods have a significant impact on health, and individual responses to nutritional factors vary. This variability among humans can be considered a basis for developing personalized or precision nutrition. Fermented foods (FF) contain a wide range of macro- and micronutrients, bioactive compounds, and live or dead microorganisms. FF represent a diverse range of products and have garnered significant interest due to their potential health benefits. However, consistent evidence remains limited, possibly due to heterogeneity in individual responses. Objectives The objective of this review is to assess and compile existing evidence on the variable responses of populations to FF and to determine whether FF could be integrated into a precision nutrition strategy. Design Interventional and observational human studies were systematically collected. The publication identified the main factors likely to contribute to variable responses to FF across all health outcomes. The question was systematically addressed to assess the available evidence and identify knowledge gaps, guiding future research. A pragmatic approach was employed, following EFSA health claim guidelines, which require an assessment of food characteristics and mechanisms of action, as well as conducting a systematic search of human interventional studies. A similar approach was used to analyze data extracted from observational studies. The population included all humans (healthy and non-healthy, of all ages), encompassing both observational and interventional studies. The intervention consisted of the ingestion of any FF, while the control was defined as the absence or lower consumption of FF or consumption of a corresponding non-FF. Outcomes included all markers of the population's health status. Results The main factors contributing to variable responses to FF across all health outcomes were related to initial phenotypic characteristics (biological sex, geographical origin, hormonal status, and age), baseline health status [metabolic syndrome [MetS], chronic metabolic pathologies, cancer, and psychological disorders], and genetic background. Additionally, since the gut microbiota is person-specific and influences metabolic responses, particular attention was paid to its functions and role in the variability of population responses to FF. Conclusion Collectively, this review represents a first step toward evaluating the feasibility of using FF in tailored nutritional strategies. Systematic review registration https://osf.io/69d3f/overview .

    ano.nymous@ccsd.cnrs.fr.invalid (Christèle Humblot) 17 Dec 2025

    https://hal.inrae.fr/hal-05422050v1
  • [hal-03856549] Faecal microbiota study reveals specific dysbiosis in spondyloarthritis

    Altered microbiota composition or dysbiosis is suspected to be implicated in the pathogenesis of chronic inflammatory diseases, such as spondyloarthritis (SpA) and rheumatoid arthritis (RA). Methods 16S ribosomal RNA gene sequencing was performed on faecal DNA isolated from stool samples in two consecutive cross-sectional cohorts, each comprising three groups of adult volunteers: SpA, RA and healthy controls (HCs). In the second study, HCs comprised a majority of aged-matched siblings of patients with known HLA-B27 status. Alpha and beta diversities were assessed using QIIME, and comparisons were performed using linear discriminant analysis effect size to examine differences between groups. Results In both cohorts, dysbiosis was evidenced in SpA and RA, as compared with HCs, and was disease specific. A restriction of microbiota biodiversity was detected in both disease groups. The most striking change was a twofold to threefold increased abundance of Ruminococcus gnavus in SpA, as compared with both RA and HCs that was significant in both studies and positively correlated with disease activity in patients having a history of inflammatory bowel disease (IBD). Among HCs, significant difference in microbiota composition were also detected between HLA-B27+ and HLA-B27 negative siblings, suggesting that genetic background may influence gut microbiota composition. Conclusion Our results suggest that distinctive dysbiosis characterise both SpA and RA and evidence a reproducible increase in R. gnavus that appears specific for SpA and a marker of disease activity. This observation is consistent with the known proinflammatory role of this bacteria and its association with IBD. It may provide an explanation for the link that exists between SpA and IBD.

    ano.nymous@ccsd.cnrs.fr.invalid (Maxime Breban) 16 Nov 2022

    https://hal.inrae.fr/hal-03856549v1
  • [mnhn-02291865] Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur

    Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze.jlr Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety.

    ano.nymous@ccsd.cnrs.fr.invalid (Fabien Pifferi) 27 May 2020

    https://mnhn.hal.science/mnhn-02291865v1
  • [hal-03695580] Inferring characteristics of bacterial swimming in biofilm matrix from time-lapse confocal laser scanning microscopy

    Biofilms are spatially organized communities of microorganisms embedded in a self-produced organic matrix, conferring to the population emerging properties such as an increased tolerance to the action of antimicrobials. It was shown that some bacilli were able to swim in the exogenous matrix of pathogenic biofilms and to counterbalance these properties. Swimming bacteria can deliver antimicrobial agents in situ, or potentiate the activity of antimicrobial by creating a transient vascularization network in the matrix. Hence, characterizing swimmer trajectories in the biofilm matrix is of particular interest to understand and optimize this new biocontrol strategy in particular, but also more generally to decipher ecological drivers of population spatial structure in natural biofilms ecosystems. In this study, a new methodology is developed to analyze time-lapse confocal laser scanning images to describe and compare the swimming trajectories of bacilli swimmers populations and their adaptations to the biofilm structure. The method is based on the inference of a kinetic model of swimmer populations including mechanistic interactions with the host biofilm. After validation on synthetic data, the methodology is implemented on images of three different species of motile bacillus species swimming in a Staphylococcus aureus biofilm. The fitted model allows to stratify the swimmer populations by their swimming behavior and provides insights into the mechanisms deployed by the micro-swimmers to adapt their swimming traits to the biofilm matrix.

    ano.nymous@ccsd.cnrs.fr.invalid (Guillaume Ravel) 20 Jun 2022

    https://hal.inrae.fr/hal-03695580v4
  • [hal-02914093] Comprehensive proteomic analysis of camel milk-derived extracellular vesicles

    Extracellular vesicles were recovered by optimized density gradient ultracentrifugation from milk of Camelus (C.) dromedarius, C. bactrianus and hybrids reared in Kazakhstan, visualized by transmission electron microscopy and characterized by nanoparticle tracking analysis. Purified extracellular vesicles had a heterogeneous size distribution with diameters varying between 25 and 170 nm, with average yield of 9.49 x 108 - 4.18 x 1010 particles per milliliter of milk. Using a comprehensive strategy combining classical and advanced proteomic approaches an extensive LC-MS/MS proteomic analysis was performed of EVs purified from 24 camel milks (C. bactrianus, n=8, C. dromedarius, n=10, and hybrids, n=6). A total of 1,010 unique proteins involved in different biological processes were thus identified, including most of the markers associated with small extracellular vesicles, such as CD9, CD63, CD81, HSP70, HSP90, TSG101 and ADAM10. Camel milk-derived EV proteins were classified according to biological processes, cellular components and molecular functions using gene-GO term enrichment analysis of DAVID 6.8 bioinformatics resource. Camel milk-derived EVs were mostly enriched with exosomal proteins. The most prevalent biological processes of camel milk-derived EV proteins were associated with exosome synthesis and its secretion processes (such as intracellular protein transport, translation, cell-cell adhesion and protein transport, and translational initiation) and were mostly engaged in molecular functions such as Poly(A) RNA and ATP binding, protein binding and structural constituent of ribosome. Proteomic studies of camel milk and sub-fractions thereof, such as casein, whey, or the milk fat globule membrane (MFGM) have revealed a plethora of bioactive proteins and peptides beneficial for developing immune and metabolic systems (Casado et al., 2008; Kussmann and Van Bladeren, 2011). By contrast, camel milk-derived EVs are still a largely uncharted proteomic terrain, although we know that milk-derived EVs carry cell origin-specific cargo and transport both bioactivity and information between cells (de la Torre Gomez et al., 2018).

    ano.nymous@ccsd.cnrs.fr.invalid (A. Ryskaliyeva) 11 Aug 2020

    https://hal.inrae.fr/hal-02914093v1
  • [hal-02152871] Gut bacteria are critical for optimal muscle functiona potential link with glucose homeostasis

    Gut microbiota is involved in the development of several chronic diseases, including diabetes, obesity and cancer, through its interactions with the host organs. It has been suggested that the cross-talk between gut microbiota and skeletal muscle plays a role in different pathological conditions, such as intestinal chronic inflammation and cachexia. However, it remains unclear whether gut microbiota directly influences skeletal muscle function. In this work, we studied the impact of gut microbiota modulation on mice skeletal muscle function and investigated the underlying mechanisms. We determined the consequences of gut microbiota depletion after treatment with a mixture of broad spectrum antibiotics for 21 days and after 10-days natural reseeding. We found that in gut microbiota-depleted mice, running endurance was decreased, as well as the extensor digitorum longus muscle fatigue index in an ex vivocontractile test. Importantly, the muscle endurance capacity was efficiently normalized by natural reseeding. Theseendurance changes werenot relatedto variationin muscle mass, fiber typology or mitochondrial function. However, several pertinent glucose metabolism markers such as ileum gene expression of short fatty acidchain and glucose transporters,Gpr41and Sglt1and muscle glycogen level, paralleled the muscle endurance changes observed after ATB treatment and reseeding. As glycogen is a key energetic substrate for prolonged exercise, modulating itsmuscle availability via gut microbiota represents one potent mechanism that can contribute to the gut microbiota/skeletal muscle axis. Taken together, our results strongly support the hypothesis that gut bacteria are required for host optimal skeletal muscle function.

    ano.nymous@ccsd.cnrs.fr.invalid (Kevin Nay) 01 Jul 2019

    https://univ-rennes.hal.science/hal-02152871v1
  • [anses-04453263] Avis de l'Anses relatif à l’évaluation des substances inscrites au programme de travail 2021 de l’Agence dans le cadre de la deuxième stratégie nationale sur les perturbateurs endocriniens (SNPE2) : Mélamine (n°CAS : 108-78-1)

    La deuxième Stratégie nationale sur les perturbateurs endocriniens (SNPE2) répond à la nécessité d’agir face aux questions que soulèvent les perturbateurs endocriniens. Lancée en 2019, elle avait pour principal objectif de réduire l’exposition des populations et de l’environnement à ces substances et comporte notamment un volet dédie à l’évaluation du caractère perturbateur endocrinien des substances chimiques.Le 8 octobre 2019, l’Agence nationale de sécurité sanitaire (Anses) a été saisie par les Ministères de la Transition écologique et des Solidarités et de la Santé pour la mise en œuvre des actions de la SNPE2 relatives à:1) L’expertise des substances chimiques en vue de proposer la reconnaissance des dangers de perturbateurs endocriniens au titre des règlements européens ;2) La coordination des travaux de l’ANSM et de l’Anses sur les perturbateurs endocriniens afin de renforcer l’évaluation des dangers et des risques des substances pour leur potentiel caractère de perturbateurs endocriniens dans les cosmétiques et les produits de santé ;3) La publication d’une liste priorisée de substances à évaluer pour leur potentiel caractère de perturbateurs endocriniens et d’une liste de substances catégorisées (perturbateurs endocriniens avérés, présumés, suspectés).Dans le cadre de l’action n°3 de cette stratégie, l’Anses a publié le 13 avril 2021 une liste desubstances d’intérêt pour leur potentiel caractère de perturbateurs endocriniens (PE) ainsi qu’une méthodologie visant à prioriser l’évaluation de ces substances afin de confirmer ou d’infirmer leur caractère de perturbateurs endocriniens. A l’issue de ce travail de priorisation, l’Anses a établi une liste de 16 substances pour lesquelles les travaux d’évaluation méritaient d’être complétés ou accélérés. Cette liste de 16 substances jugées prioritaires a été présentée à une réunion commune des comités d’orientation thématique (COT) de l’Anses. Ces instances consultatives constituent des espaces de dialogue et d’échanges avec les parties prenantes de l’Agence incluant les différents collèges représentés au conseil d’administration et des membres d’organisations de la société civile impliquées sur les champs de compétence de l’Anses. Ils ont vocation à épauler le conseil d’administration dans l’expression des besoins en termes d’évaluation des risques et de recherche et la définition des orientations stratégiques de l’Agence, en lui faisant remonter les préoccupations dominantes de la société civile dans le domaine de compétence de l’Anses. Le 15 avril 2021, les membres du comité d’orientation thématique sur les perturbateurs endocriniens (InterCOT PE) ont été invités à nommer jusqu’à 3 substances leur apparaissant comme prioritaires à évaluer pour leur potentiel caractère PE.Les résultats de cette consultation ont permis la hiérarchisation de ces 16 substances tenant compte de leurs dangers, des expositions et du niveau de préoccupation sociétale qu’elles suscitent. Suite à cette hiérarchisation la mélamine a été classée comme une substance à évaluer de manière prioritaire.L’agence a souhaité rendre compte de son évaluation et de ses conclusions à travers la rédaction d’une « analyse des options de gestion des risques règlementaires » (Regulatory management option analysis ou RMOA), utilisé dans le cadre de REACH. Ce format permet, simultanément, d’apporter une aide à la décision aux ministères français sur la /les mesure(s) de gestion des risques la/les plus appropriée(s) à adopter et de partager au niveau européen les résultats des travaux de l’agence menés dans le cadre de la SNPE2.Les RMOA sont réalisés selon un format standard européen et comportent les informationssuivantes :- les éléments de contexte relatifs aux informations disponibles et à l’encadrement règlementaire existant des substances ;- les informations disponibles sur les dangers et les usages des substances, les tonnages, les risques pour la santé humaine ou l’environnement, les cas d’usages susceptibles d’entraîner des effets néfastes sur la santé et/ou l’environnement, etc…, en fonction des problématiques couvertes dans le RMOA ;- une justification de la nécessité de la mise en œuvre de mesures de gestion du risque au niveau européen ; l’identification des différentes options de gestion du risque disponibles dans le cadre du règlement REACH, du règlement CLP, ou s’appuyant sur d’autres outils législatifs et réglementations sectorielles existants en fonction des usages identifiés de ces substances.

    ano.nymous@ccsd.cnrs.fr.invalid (Sakina Mhaouty-Kodja) 12 Feb 2024

    https://anses.hal.science/anses-04453263v1
  • [anses-04616159] Avis de l'Anses relatif à l’analyse des options de gestion réglementaires du disulfure de carbone (n°CAS : 75-15-0) dans le cadre de la réglementation REACH

    En application des protocoles d’accord du 28 juillet 2017 et du 7 juin 2022 relatifs à l’organisation de l’Anses et des ministères de tutelle pour la mise en œuvre des Règlements REACh et CLP, un programme de travail annuel est établi entre l’Anses et les ministères de tutelle. Au sein de ce programme de travail, l’Anses identifie des substances chimiques pour lesquelles des risques pour la santé humaine et/ou l’environnement sont observés et analyse les options de gestion des risques règlementaires (Regulatory Management Option Analysis ou RMOA) afin d’apporter une aide à la décision aux ministères sur la /les mesure(s) de gestion des risques la/les plus appropriée(s) à adopter. Au cas par cas, elle approfondit dans le cadre du RMOA certains champs d’évaluation des dangers et des risques. Le programme de travail 2022 comportait la réalisation d’une analyse des options de gestion règlementaires concernant le disulfure de carbone (N° CAS : 75-15-0). Le choix de cette substance fait suite aux conclusions de l’Anses dans le cadre du règlement REACh (Anses, 2021 ; 2022). Les RMOA sont réalisés selon le format standard européen et comportent les informations suivantes : - les éléments de contexte relatifs aux informations disponibles et à l’encadrement règlementaire existant des substances ; - les informations disponibles sur les dangers et les usages des substances, les tonnages, les risques pour la santé humaine ou l’environnement, les cas d’usages susceptibles d’entraîner des effets néfastes sur la santé et/ou l’environnement, etc…, en fonction des problématiques couvertes dans le RMOA ; - une justification de la nécessité de la mise en œuvre de mesures de gestion du risque au niveau européen ; - l’identification des différentes options de gestion du risque disponibles dans le cadre du règlement REACh, du règlement CLP, ou s’appuyant sur d’autres outils législatifs et réglementations sectorielles existants en fonction des usages identifiés de ces substances

    ano.nymous@ccsd.cnrs.fr.invalid (Luc Belzunces) 18 Jun 2024

    https://anses.hal.science/anses-04616159v1
  • [hal-05279637] Alterations in gut microbiota characteristics along a type 2 diabetes risk gradient linked with family history

    Type 2 diabetes (T2D) is a major global health issue, with growing evidence linking it to gut microbiome changes. However, whether these alterations precede T2D onset and act as predictors, risk factors, or contributors remains unclear. This study analyzed the gut microbiota of 192 individuals from the French NutriNet-Santé cohort, divided into four groups: non-T2D adults with no (n = 47), one (n = 48), or two (n = 51) T2D-affected parents, and T2D-affected adults (n = 46). A progressive microbiota shift was observed in non-T2D groups based on parental history, converging toward the T2D profile. Changes included altered enterotype distribution, increased oral-associated species, disrupted ecological networks, and a shift in Gram-positive-to-negative ratios. Notably, Prevotella copri abundance increased, alongside bacteria potentially enhancing branched-chain amino acid (BCAA), lipopolysaccharide (LPS), and acetate production. Diet also influenced microbiota patterns, with sweet product intake, vitamin levels, and copper/zinc ratios playing roles. A gradual microbiome transition from non-diabetic to T2D participants underscores its association with family history-based risk. While these shifts may reflect or drive T2D progression, further studies are needed to confirm these findings and explore their potential for preventive strategies.

    ano.nymous@ccsd.cnrs.fr.invalid (Oscar Gitton-Quent) 23 Sep 2025

    https://hal.inrae.fr/hal-05279637v1
  • [hal-03339765] Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3

    The commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo. Our results showed that F. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.

    ano.nymous@ccsd.cnrs.fr.invalid (Marion Lenoir) 09 Sep 2021

    https://hal.inrae.fr/hal-03339765v1
  • [hal-03824840] Modulation of the PI3K/Akt/mTOR signaling pathway by probiotics as a fruitful target for orchestrating the immune response

    The mammalian target of rapamycin (mTOR) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B or Akt (PKB/Akt) signaling pathways are considered as two but somewhat interconnected significant immune pathways which play complex roles in a variety of physiological processes as well as pathological conditions. Aberrant activation of PI3K/Akt/mTOR signaling pathways has been reported to be associated in a wide variety of human diseases. Over the past few years, growing evidence in in vitro and in vivo models suggest that this sophisticated and subtle cascade mediates the orchestration of the immune response in health and disease through exposure to probiotics. An expanding body of literature has highlighted the contribution of probiotics and PI3K/Akt/mTOR signaling pathways in gastrointestinal disorders, metabolic syndrome, skin diseases, allergy, salmonella infection, and aging. However, longitudinal human studies are possibly required to verify more conclusively whether the investigational tools used to understand the regulation of these pathways might provide effective approaches in the prevention and treatment of various disorders. In this Review, we summarize the experimental evidence from recent peer-reviewed studies and provide a brief overview of the causal relationship between the effects of probiotics and their metabolites on the components of PI3K/Akt/mTOR signaling pathways and human disease.

    ano.nymous@ccsd.cnrs.fr.invalid (Amir Hossein Mohseni) 21 Oct 2022

    https://hal.inrae.fr/hal-03824840v1
  • [hal-04535966] Anti-S-layer monoclonal antibodies impact <i>Clostridioides difficile</i> physiology

    Clostridioides difficile (C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults which is characterized by high levels of recurrence and mortality. Surface (S)-layer Protein A (SlpA), the most abundantly expressed protein on the bacterial surface, plays a crucial role in the early stages of infection although the nature of its involvement in C. difficile physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and have been correlated with improved outcomes of C. difficile infection (CDI). However, the precise mechanisms by which anti-S-layer antibodies confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting the S-layer of reference strain 630. Characterization of these mAbs unraveled important roles for the S-layer protein in growth, toxin secretion, and biofilm formation by C. difficile, with differential and even opposite effects of various anti-SlpA mAbs on these functions. Moreover, one anti-SlpA mAb impaired C. difficile growth and conferred sensitivity to lysozyme-induced lysis. The results of this study show that anti-S-layer antibody responses can be beneficial or harmful for the course of CDI and provide important insights for the development of adequate S-layer-targeting therapeutics.

    ano.nymous@ccsd.cnrs.fr.invalid (Lise Hunault) 07 Apr 2024

    https://hal.inrae.fr/hal-04535966v1
  • [hal-04908276] Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism

    Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.

    ano.nymous@ccsd.cnrs.fr.invalid (Naika Prince) 23 Jan 2025

    https://hal.inrae.fr/hal-04908276v1
  • [hal-00961711] Ecology and metabolism of the beneficial intestinal commensal bacterium Faecalibacterium prausnitzii

    Faecalibacterium prausnitzii is a major commensal bacterium, and its prevalence is often decreased in conditions of intestinal dysbiosis. The phylogenic identity of this bacterium was described only recently. It is still poorly characterized, and its specific growth requirements in the human gastrointestinal tract are not known. In this review, we consider F. prausnitzii metabolism, its ecophysiology in both humans and animals, and the effects of drugs and nutrition on its population. We list important questions about this beneficial and ubiquitous commensal bacterium that it would be valuable to answer.

    ano.nymous@ccsd.cnrs.fr.invalid (Sylvie Miquel) 10 Feb 2025

    https://hal.science/hal-00961711v1
  • [hal-03518769] Alteration of the gut microbiota following SARS-CoV-2 infection correlates with disease severity in hamsters

    Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster model. Our data confirmed that this model recapitulates some hallmark features of the human disease in the lungs. We further showed that SARS-CoV-2 infection associated with mild intestinal inflammation, relative alteration in intestinal barrier property and liver inflammation and altered lipid metabolism. These changes occurred concomitantly with an alteration of the gut microbiota composition over the course of infection, notably characterized by a higher relative abundance of deleterious bacterial taxa such as Enterobacteriaceae and Desulfovibrionaceae. Conversely, several members of the Ruminococcaceae and Lachnospiraceae families, including bacteria known to produce the fermentative products short-chain fatty acids (SCFAs), had a reduced relative proportion compared to non-infected controls. Accordingly, infection led to a transient decrease in systemic SCFA amounts. SCFA supplementation during infection had no effect on clinical and inflammatory parameters. Lastly, a strong correlation between some gut microbiota taxa and clinical and inflammation indices of SARS-CoV-2 infection severity was evidenced. Collectively, alteration of the gut microbiota correlates with disease severity in hamsters making this experimental model valuable for the design of interventional, gut microbiota-targeted, approaches for the control of COVID-19.

    ano.nymous@ccsd.cnrs.fr.invalid (Valentin Sencio) 10 Jan 2022

    https://hal.sorbonne-universite.fr/hal-03518769v1
  • [inserm-03755432] Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk

    Some cardiometabolic risk factors such as dyslipidemia and insulin resistance are known to be associated with low gut microbiota richness. A link between gut microbiota richness and the diversity of consumed dietary fibers (DF) has also been reported. We introduced a larger diversity of consumed DF by using a daily consumed bread in subjects at cardiometabolic risk and assessed the impacts on the composition and functions of gut microbiota as well as on cardiometabolic profile. Thirty-nine subjects at cardiometabolic risk were included in a double-blind, randomized, cross-over, twice 8-week study, and consumed daily 150 g of standard bread or enriched with a 7-dietary fiber mixture (5.55 g and 16.05 g of fibers, respectively). Before and after intervention, stool samples were collected for gut microbiota analysis from species determination down to gene-level abundance using shotgun metagenomics, and cardiometabolic profile was assessed. Multi-fiber bread consumption significantly decreased Bacteroides vulgatus, whereas it increased Parabacteroides distasonis, Fusicatenibacter saccharivorans, an unclassified Acutalibacteraceae and an unclassified Eisenbergiella (q \textless 0.1). The fraction of gut microbiota carrying the gene coding for five families/subfamilies of glycoside hydrolases (CAZymes) were also increased and negatively correlated with peaks and total/incremental area under curve (tAUC/iAUC) of postprandial glycemia and insulinemia. Compared to control bread, multi-fiber bread decreased total cholesterol (-0.42 mM; q \textless 0.01), LDL cholesterol (-0.36 mM; q \textless 0.01), insulin (-2.77 mIU/l; q \textless 0.05), and HOMA (-0.78; q \textless 0.05). In conclusion, increasing the diversity of DF in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile.

    ano.nymous@ccsd.cnrs.fr.invalid (H. Ranaivo) 22 Aug 2022

    https://inserm.hal.science/inserm-03755432v1
  • [hal-01608260] Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance

    The trillions of bacterial cells that colonize the mammalian digestive tract influence both host physiology and the fate of dietary compounds. Gnotobionts and fecal transplantation have been instrumental in revealing the causal role of intestinal bacteria in energy homeostasis and metabolic dysfunctions such as type-2 diabetes. However, the exact contribution of gut bacterial metabolism to host energy balance is still unclear and knowledge about underlying molecular mechanisms is scant. We have previously characterized cecal bacterial community functions and host responses in diet-induced obese mice using omics approaches. Based on these studies, we here discuss issues on the relevance of mouse models, give evidence that the metabolism of cholesterol-derived compounds by gut bacteria is of particular importance in the context of metabolic disorders and that dominant species of the family Coriobacteriaceae are good models to study these functions.

    ano.nymous@ccsd.cnrs.fr.invalid (Thomas Clavel) 03 Oct 2017

    https://hal.science/hal-01608260v1
  • [hal-04707080] Improved gut microbiome recovery following drug therapy is linked to abundance and replication of probiotic strains

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Jamie Fitzgerald) 24 Sep 2024

    https://hal.inrae.fr/hal-04707080v1
  • [hal-03339876] Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening

    Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except forEscherichia coliandEnterococcusspp., which became dominant. Both the alpha and beta-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase ofE. coliandEnterococcusspp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved alpha-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients' outcome.

    ano.nymous@ccsd.cnrs.fr.invalid (Thomas Hueso) 04 Sep 2024

    https://hal.inrae.fr/hal-03339876v1
  • [hal-02628590] Mucosa-associated microbiota dysbiosis in colitis associated cancer

    Gut microbiota dysbiosis has been associated with inflammatory bowel diseases (IBD). In colorectal cancer, the gut microbiota has also been recognized as potentially involved in aggravating or favoring the tumor development. However, very little is known on the structure and role of the microbiota in colitis associated cancer (CAC), an important complication of IBD in human. Here we analyzed the bacterial and fungal composition of the mucosa associated microbiota of patients suffering CAC, sporadic cancer (SC) and of healthy subjects (HS) by barcode sequences analysis on the following cohort: 7 CAC patients, 10 SC patients and 10 HS using 16S (MiSeq) and ITS2 (pyrosequencing) sequencing, for bacteria and fungi respectively. Mucosa-associated bacterial microbiota in CAC was significantly different from the ones in SC or in HS, while the fungal showed no differences. Comparison between mucosa-associated microbiota on the tumor site or in normal mucosa near the tumor showed very similar patterns. The global mucosa-associated bacterial microbiota in cancer patients was characterized by a restriction in biodiversity but no change for the fungal community. Compared to SC, CAC was characterized by an increase of Enterobacteriacae family and Sphingomonas genus and a decrease of Fusobacterium and Ruminococcus genus. Our study confirms the alteration of the mucosa-associated bacterial microbiota in IBD and SC. Although the cohort is limited in number, this is the first evidence of the existence of an altered bacterial microbiota in CAC clearly different from the one in SC patients.

    ano.nymous@ccsd.cnrs.fr.invalid (Mathias Lavie-Richard) 27 May 2020

    https://hal.inrae.fr/hal-02628590v1
  • [hal-04645842] The microbiota and the host organism switch between cooperation and competition based on dietary iron levels

    The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (&amp;lt;6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2 alpha. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced alpha-diversity of microbiota, and led to Lactobacillaceae becoming particularly more abundant after 60 days of privation. By inoculating GF mice with a simplified bacterial mixture, we show that the iron-depleted host favors the gut fitness of Bifidobacterium longum

    ano.nymous@ccsd.cnrs.fr.invalid (Marie-Louise Noordine) 12 Jul 2024

    https://hal.inrae.fr/hal-04645842v1
  • [hal-05168787] Unraveling the gut-skin axis in atopic dermatitis: exploiting insights for therapeutic strategies

    Gut microbiota exert functions of high importance in the intestine. Furthermore, there is increasing evidence for its role in immune regulation and maintenance of homeostasis in many physiological processes taking place in distant tissues. In particular, in this review, we explore the impact of metabolites produced by the gut microbiota on the development of atopic dermatitis (AD). Probiotics and prebiotics balance the microbiota and promote the generation of bacterial metabolites, such as short-chain fatty acids and tryptophan derivates, which promote the regulation of the exacerbated AD immune response through regulatory T cells and IL-10 and TGF-β cytokines. Metabolites also have a direct action on keratinocytes once they reach the bloodstream. Besides, probiotics decrease the levels of metabolites associated with AD onset, such as phenols. Understanding all these crosstalk processes between the gut and the skin reveals a number of possibilities, mainly through the manipulation of the gut microbiome, which may represent therapeutic strategies that can contribute to the standard treatments of AD patients to improve their quality of life.

    ano.nymous@ccsd.cnrs.fr.invalid (Marcela Rios-Carlos) 18 Jul 2025

    https://hal.inrae.fr/hal-05168787v1

Contact

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