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HAL : Dernières publications

  • [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-05298898] Differential translocation of bacteriophages across the intestinal barrier in health and Crohn’s disease

    SUMMARY Impaired intestinal barrier function is a major feature of Crohn’s disease (CD), leading to exacerbated inflammation in response to the microbiota. In this context, the translocation of intestinal bacteriophages (phages) and their effects on the host have been little investigated. We used phage fluorescence imaging coupled with ex-vivo and in-vitro models that mimic physiological and inflammatory conditions and found that phages can translocate across the intestinal barrier without disrupting its integrity. Although the translocation rate across the intestinal epithelium depended on phage morphology and the condition of the barrier, these factors did not influence the crossing of phage across the vascular endothelium. Virome analysis confirmed that viral sequences shared between blood and stool samples are more abundant in CD patients than healthy subjects, indicating that a barrier defect facilitates phage translocation from the gut to the bloodstream.

    ano.nymous@ccsd.cnrs.fr.invalid (Clara Douadi) 06 Oct 2025

    https://hal.inrae.fr/hal-05298898v1
  • [hal-05484226] Evolution of T cell receptor beta loci in salmonids

    T-cell mediated immunity relies on a vast array of antigen specific T cell receptors (TR). Characterizing the structure of TR loci is essential to study the diversity and composition of T cell responses in vertebrate species. The lack of good-quality genome assemblies, and the difficulty to perform a reliably mapping of multiple highly similar TR sequences, have hindered the study of these loci in non-model organisms. High-quality genome assemblies are now available for the two main genera of Salmonids, Salmo and Oncorhynchus . We present here a full description and annotation of the TRB loci located on chromosomes 19 and 25 of rainbow trout ( Oncorhynchus mykiss ). To get insight about variations of the structure and composition of TRB locus across salmonids, we compared rainbow trout TRB loci with other salmonid species and confirmed that the basic structure of salmonid TRB locus is a double set of two TRBV-D-J-C loci in opposite orientation on two different chromosomes. Our data shed light on the evolution of TRB loci in Salmonids after their whole genome duplication (WGD). We established a coherent nomenclature of salmonid TRB loci based on comprehensive annotation. Our work provides a fundamental basis for monitoring salmonid T cell responses by TRB repertoire sequencing.

    ano.nymous@ccsd.cnrs.fr.invalid (Pierre Boudinot) 29 Jan 2026

    https://hal.inrae.fr/hal-05484226v1
  • [hal-05283634] Corrigendum : Lacticaseibacillus casei CNCM I-5663 supplementation maintained muscle mass in a model of frail rodents.

    The aim of this study was to identify a probiotic-based strategy for maintaining muscle anabolism in the elderly. In previous research, we found that individuals experiencing short bowel syndrome (SBS) after an intestinal resection displayed beneficial metabolic adjustments that were mediated by their gut microbes. Thus, these bacteria could potentially be used to elicit similar positive effects in elderly people, who often have low food intake and thus develop sarcopenia. Gut bacterial strains from an SBS patient were evaluated for their ability to (1) maintain Caenorhabditis elegans survival and muscle structure and (2) promote protein anabolism in a model of frail rodents (18-month-old rats on a food-restricted diet: 75% of ad libitum consumption). We screened a first set of bacteria in C. elegans and selected two Lacticaseibacillus casei strains (62 and 63) for further testing in the rat model. We had four experimental groups: control rats on an ad libitum diet (AL); non-supplemented rats on the food-restricted diet (R); and two sets of food-restricted rats that received a daily supplement of one of the strains (∼109 CFU; R+62 and R+63). We measured lean mass, protein metabolism, insulin resistance, cecal short-chain fatty acids (SCFAs), and SCFA receptor expression in the gut. Food restriction led to decreased muscle mass [-10% vs. AL (p < 0.05)]. Supplementation with strain 63 tempered this effect [-2% vs. AL (p > 0.1)]. The mechanism appeared to be the stimulation of the insulin-sensitive p-S6/S6 and p-eIF2α/eIF2α ratios, which were similar in the R+63 and AL groups (p > 0.1) but lower in the R group (p < 0.05). We hypothesize that greater SCFA receptor sensitivity in the R+63 group promoted gut-muscle cross talk [GPR41: +40% and GPR43: +47% vs. R (p < 0.05)]. Hence, strain 63 could be used in association with other nutritional strategies and exercise regimes to limit sarcopenia in frail elderly people.

    ano.nymous@ccsd.cnrs.fr.invalid (Muriel Giron) 25 Sep 2025

    https://hal.inrae.fr/hal-05283634v1
  • [tel-05483135] Régulation des cellules entéroendocrines par le microbiote intestinal le long de l'intestin : vers une implication du métabolisme cellulaire

    Les cellules entéroendocrines (CEE) sont essentielles dans l'épithélium intestinal en produisant des hormones régulant entre autres le métabolisme énergétique, la satiété, la digestion et le transit intestinal. Ces hormones sont sécrétées en réponse à différents stimuli, notamment nutritionnels et microbiens, permettant une réponse adaptée à la prise alimentaire ou à un changement de l'activité du microbiote intestinal. Ce dernier regroupe l'ensemble des microorganismes nichés dans l'intestin, majoritairement des bactéries, qui interagissent avec l'hôte au travers de leur contribution à l'extraction des nutriments fournissant des substrats énergétiques aux cellules de l'hôte, modulant son activité métabolique, la barrière intestinale et l'immunité. Les CEE expriment de nombreux récepteurs qui les rendent particulièrement sensibles aux métabolites produits par le microbiote intestinal. Le lien étroit entre microbiote et hormones intestinales est illustré par des niveaux circulants d'hormones, telles que GLP-1, dérégulés chez les animaux axéniques ou traités aux antibiotiques. Par ailleurs, différentes sous-populations de CEE sont dispersées le long du tractus intestinal, permettant des réponses locales spécifiques aux modifications de l'environnement.Ce travail de thèse vise à mieux comprendre comment les fonctions des différentes sous-populations de CEE sont régulées. En particulier, l'objectif de cette étude était de comprendre comment, en absence de pathologie, le microbiote intestinal module les CEE et leur production d'hormones intestinales. En plus de mener cette étude à travers différentes régions intestinales, j'ai étudié la cinétique de mise en place des adaptations des CEE à un changement de l'environnement microbien tout en analysant d'éventuels dimorphismes sexuels dans la réponse des CEE.Afin de comprendre comment l'activité des CEE est régulée par le microbiote intestinal, le microbiote de souris a été appauvri par antibiothérapie à spectre large. L'expression génique des hormones intestinales a été mesurée à différents temps post-déplétion et dans diverses régions intestinales. L'utilisation de souris génétiquement modifiées produisant une protéine fluorescente spécifiquement dans les CEE, a permis de trier ces cellules et d'étudier les réponses spécifiques des CEE par rapport à l'épithélium.Au cours de cette thèse, j'ai pu montrer que l'absence de microbiote intestinal entraîne une adaptation transcriptionnelle des CEE produisant plus certaines hormones intestinales spécifiquement selon les régions intestinales. En outre, les réponses transcriptionnelles des CEE triées sont différentes du reste de l'épithélium intestinal, indiquant une réponse spécifique des CEE au microbiote intestinal. L'analyse des voies KEGG indique que les voies du métabolisme sont particulièrement altérées par l'absence de microbiote dans les CEE. Des analyses d'activités enzymatiques et de modulations métaboliques sur modèles organoïdes soutiennent l'hypothèse d'une implication du remodelage du métabolisme des CEE dans l'altération de leurs fonctions par le microbiote intestinal.Ces observations soulignent une importante spécificité de la modulation fonctionnelle des CEE par le microbiote intestinal en fonction des régions intestinales. Cette réponse hétérogène des CEE pourrait être liée à des facteurs environnementaux locaux ou à des facteurs endogènes comme des régulations épigénétiques. Par ailleurs, la modulation de l'environnement microbien influence différemment l'activité des divers sous-types de CEE. Cette spécificité ouvre des perspectives thérapeutiques, la production de certaines hormones intestinales pourrait être ciblée via les voies sensibles au microbiote, notamment dans le contexte de maladies métaboliques comme le diabète. Enfin, l'activité fonctionnelle des CEE semble intrinsèquement liée à leur métabolisme cellulaire qui apparaît ainsi comme un levier potentiel majeur de la régulation de l'activité entéroendocrine.

    ano.nymous@ccsd.cnrs.fr.invalid (Delphine Polvé) 29 Jan 2026

    https://theses.hal.science/tel-05483135v1
  • [hal-05473389] The food grade bacterium Lactobacillus helveticus VEL12193 promotes autophagy by releasing membrane vesicles

    BACKGROUND: Autophagy-related processes are crucial for maintaining cellular homeostasis in eukaryotic organisms. While alterations of these processes have been strongly linked to specific human disorders, including inflammatory bowel disease, neurodegenerative diseases, and metabolic syndromes, long-term autophagy stimulation appears to be safe and to extend lifespan in model organisms. Several studies indicate that gut microbiota or derived metabolites can modulate host autophagy at the gut mucosa level but also in peripheral organs. Here, we investigated in vitro and in vivo the potential of bacterial species commonly used in food fermentation (ferments) or for their health benefits (probiotics) to modulate host autophagy. METHODS: We screened 11 bacterial strains (lactobacilli and bifidobacteria) in vitro for autophagy induction in human epithelial cells. The most effective strain identified in vitro was then tested in vivo through long-term dietary supplementation in mice to confirm its pro-autophagic effects in the gut and a distant organ, the retina. RESULTS: In vitro screening of the 11 bacterial strains revealed a strain-dependent ability of bacteria to stimulate autophagy in human epithelial cells. The Lactobacillus helveticus strain VEL12193, isolated from cheese, emerged as the strongest autophagy inducer. Long-term dietary supplementation of mice with L. helveticus VEL12193 confirmed the pro-autophagic potential of this strain, as evidenced by autophagy stimulation in the gut mucosa but also at distance, in the retina. Finally, we identified membrane vesicles (MVs) from L. helveticus as a component involved in bacteria-induced autophagy in epithelial and immune cells, with lactate and specific lipid species potentially contributing to this effect. CONCLUSION: In this study, we present evidence that intervention with ferments/probiotics stimulates autophagy in multiple cell types and organs, and we show in vitro that MVs mediate this effect. Additionally, we identify L. helveticus VEL12193 as a promising candidate for the development of healthy-aging strategies.

    ano.nymous@ccsd.cnrs.fr.invalid (Marie-Agnès Bringer) 29 Jan 2026

    https://hal.science/hal-05473389v2
  • [hal-04344498] Elimination of cefotaxime during continuous renal replacement therapy using polysulfone and polyacrylonitrile-derived filters. An in vitro assessment

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    ano.nymous@ccsd.cnrs.fr.invalid (Jessica Le Ven) 14 Dec 2023

    https://hal.science/hal-04344498v1
  • [hal-04344460] Elimination of cefepime during continuous renal replacement therapy using polysulfone and polyacrylonitrile-derived filters. An in vitro assessment

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    ano.nymous@ccsd.cnrs.fr.invalid (Valentin Maulet) 14 Dec 2023

    https://hal.science/hal-04344460v1
  • [hal-04068124] Elimination of cefotaxime using polysulfone and polyacrylonitrile-derived filters: An in vitro assessment

    Continuous renal replacement therapy (CCRT) efficiently eliminates cefotaxime. To our knowledge, there are no previous in vitro studies dealing with the disposition of cefotaxime. We studied the elimination of cefotaxime by two filters in a model mimicking a session of CRRT using the NeckEpur ® technology. The ST150 ® -polyacrylonitrile filter with the Prismaflex, Baxter-Gambro, and the AV1000 ® -polysulfone filter with the Multifiltrate Pro, Fresenius, were studied. Continuous filtration used a flowrate of 1 L/h in post-dilution only. Simulated blood flowrate was set at 200 mL/min. Routes of elimination were assessed using the NeckEpur ® technology. Cefotaxime concentrations were measured using ultra high-performance liquid chromatography, and tandem mass spectrometry. Two sessions were performed using the ST ® filter and three using the AV ® filter. Stability of cefotaxime during 6 h was assessed in triplicate with a mean variation of concentrations of 2.4 ± 1.5% at the end of the study. The mean measured initial concentration in the central compartment (CC) for the five sessions was 52.4 mg/L. The mean amount eliminated from the CC at the end of the sessions using the ST150 ® -polyacrylonitrile and the AV1000 ® -polysulfone filters were 72% and 73%, respectively. The clearances of cefotaxime from the central compartment (CC) were 1.1 and 1.2 L/h, respectively. The mean sieving coefficient were 0.99 and 0.99, respectively. The mean percentages of the amount eliminated from the CC by filtration/adsorption were 87/13% and 92/8%, respectively. Both adsorption percentages were below 15%. We conclude neither the ST150 ® -polyacrylonitrile nor the AV1000 ® -polysulfone filters result in clinically significant adsorption of cefotaxime.

    ano.nymous@ccsd.cnrs.fr.invalid (Jessica Le Ven) 13 Apr 2023

    https://hal.science/hal-04068124v1
  • [hal-03339579] Elimination of fluconazole during continuous renal replacement therapy. An in vitro assessment

    Introduction: Continuous renal replacement therapy (CRRT) efficiently eliminates fluconazole. However, the routes of elimination were not clarified. Adsorption of fluconazole by filters is a pending question. We studied the elimination of fluconazole in a model mimicking a session of CRRT in humans using the NeckEpur® model. Two filters were studied. Methods: The AV1000®-polysulfone filter with the Multifiltrate Pro. Fresenius and the ST150®-polyacrylonitrile filter with the Prismaflex. Baxter-Gambro were studied. Continuous filtration used a flowrate of 2.5 L/h in post-dilution only. Session were made in duplicate. Routes of elimination were assessed using the NeckEpur® model. Results: The mean measured initial fluconazole concentration (mean ± SD) for the four sessions in the central compartment (CC) was 14.9 ± 0.2 mg/L. The amount eliminated from the CC at the end of 6 h-session at a 2.5 L/h filtration flowrate for the AV1000®-polysulfone and the ST150®-polyacrylonitrile filters were 90%–93% and 96%–94%, respectively; the clearances from the central compartment (CC) were 2.5–2.6 and 2.4–2.3 L/h, respectively. The means of the instantaneous sieving coefficient were 0.94%–0.91% and 0.99%–0.91%, respectively. The percentages of the amount eliminated from the CC by filtration/adsorption were 100/0%–95/5% and 100/0%–100/0%, respectively. Conclusion: Neither the ST150®-polyacrylonitrile nor the AV1000®-polysulfone filters result in any significant adsorption of fluconazole.

    ano.nymous@ccsd.cnrs.fr.invalid (Frédéric Baud) 09 Sep 2021

    https://hal.inrae.fr/hal-03339579v1
  • [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
  • [hal-05473716] Cyclic exclusive enteral nutrition versus partial enteral nutrition to maintain long-term drug-free remission in paediatric Crohn's disease (CD-HOPE): an open-label, endpoint-blinded, randomised controlled trial

    Background For children with Crohn's disease, there is a marked demand for long-term nutritional treatment strategies to avoid the side-effects related to drug treatment. We aimed to investigate whether paediatric patients with Crohn's disease responding to nutritional induction therapy can be maintained in remission on dietary therapy without the use of medication or surgery. Methods In this open-label, endpoint-blinded, randomised controlled trial (CD-HOPE) done in 21 hospitals of the GETAID pédiatrique network in France, eligible patients were aged 6 years to younger than 18 years with Crohn's disease (newly diagnosed or relapsing after drug treatment) who had reached clinical remission (weighted Paediatric Crohn's Disease Activity Index [wPCDAI] ≤12·5) after induction therapy with 6–12 weeks of exclusive enteral nutrition (EEN; 100% of calories). Stratified by age (≤10 years or >10 years) and relapse status, patients were randomly assigned (1:1) using block randomisation to receive either cyclic EEN (C-EEN; 100% of daily caloric requirements) for 2 weeks every 8 weeks for at least six cycles or daily partial enteral nutrition (PEN; 25% of daily caloric requirements) for 52 weeks. Oral MODULEN IBD was used for both. Except for the 2-week intervals of EEN in the C-EEN group, food access was not restricted. The primary endpoint was relapse rate at 12 months. A relapse was defined as: (1) a wPCDAI score greater than 12·5 at two successive visits, or (2) a wPCDAI greater than 12·5 once and the need for Crohn's disease-related surgery, medication, or study exit, or (3) a wPCDAI score continuously greater than 12·5 since the last study visit, or (4) incomplete wPCDAI and moderate or severe Physician Global Assessment at any timepoint. Primary and safety analyses were performed on an intention-to-treat basis. This trial was registered on ClinicalTrials.gov (NCT02201693) and is complete. Findings Between Dec 12, 2014, and Sept 4, 2018 (last patient visit Oct 2, 2019), 112 patients were screened and 100 patients (70 boys and 30 girls) were randomly assigned to C-EEN (n=49) or PEN (n=51). Median age of participants was 12 years (IQR 11–13) in the C-EEN group and 13 years (11–14) in the PEN group. At 12 months, 24 (49%) of 49 patients had relapsed on C-EEN compared with 39 (76%) of 51 patients on PEN (adjusted odds ratio 0·29 [95% CI 0·13–0·70], p=0·0051). 19 adverse events occurred in 17 patients: four serious adverse events in four patients on PEN, not related to treatment, and 15 non-serious adverse events in 13 patients (nine in seven patients on C-EEN and six in six patients on PEN). The serious adverse events were all related to Crohn's disease relapse requiring hospitalisation for rescue therapy. Six adverse events were possibly related to study treatment: one patient in the C-EEN group reported transient vomiting and diarrhoea at the start of the first EEN cycle, one patient in the C-EEN group developed anorexia and, in the PEN group, four patients reported either weight loss, nausea, Crohn's disease relapse, or skin infection. No malignancy or death was reported in this study. Interpretation C-EEN was superior to PEN in maintaining clinical remission over 1 year in paediatric patients with Crohn's disease responding to EEN induction therapy. These findings suggest a new way to use nutritional therapy for maintaining drug-free long-term remission in patients with Crohn's disease who are responding to EEN induction therapy. Funding Assistance Publique-Hôpitaux de Paris and Nestlé Health Science.

    ano.nymous@ccsd.cnrs.fr.invalid (Bénédicte Pigneur) 23 Jan 2026

    https://u-picardie.hal.science/hal-05473716v1
  • [hal-05347161] Intestinal hepcidin overexpression promotes iron deficiency anemia and counteracts iron overload via DMT1 downregulation

    Hepcidin is the key hyposideremic hormone produced primarily by the liver. However, recent reports reveal extra-hepatic functional sources of hepcidin, including the intestine, the site of dietary iron absorption. To determine whether intestinal hepcidin may play a role in plasma iron lowering, we generated transgenic mice overexpressing the peptide specifically in this tissue. At one month of age, transgenic mice exhibited severe iron deficiency along with decreased haematological indices and a drastic suppression of liver hepcidin in response to hyposideremia. Mechanistically, we showed that intestinal hepcidin was produced in the intestine lumen, inducing a striking down-regulation of Divalent Metal Transporter 1 (DMT1) protein at the enterocyte. To confirm the capacity of hepcidin to decrease DMT1, we developed food-grade recombinant lactic acid bacteria (recLAB) genetically modified to deliver hepcidin directly into the intestinal lumen. These recLAB induced a rapid decrease of duodenal DMT1 and, most importantly, when daily orally administrated, protected against iron overload in a mouse model of hemochromatosis. Taken together, our data reveal a previously unrecognized role of intestinal hepcidin as a regulator of systemic iron homeostasis, acting on DMT1 on the apical side of enterocytes, with potential therapeutics relevance for haematological or iron disorders.

    ano.nymous@ccsd.cnrs.fr.invalid (Marion Falabrègue) 04 Nov 2025

    https://hal.inrae.fr/hal-05347161v1
  • [hal-04280847] Evolution of T cell receptor beta loci in salmonids

    T-cell mediated immunity relies on a vast array of antigen specific T cell receptors (TR). Characterizing the structure of TR loci is essential to study the diversity and composition of T cell responses in vertebrate species. The lack of good-quality genome assemblies, and the difficulty to perform a reliably mapping of multiple highly similar TR sequences, have hindered the study of these loci in non-model organisms. High-quality genome assemblies are now available for the two main genera of Salmonids, Salmo and Oncorhynchus . We present here a full description and annotation of the TRB loci located on chromosomes 19 and 25 of rainbow trout ( Oncorhynchus mykiss ). To get insight about variations of the structure and composition of TRB locus across salmonids, we compared rainbow trout TRB loci with other salmonid species and confirmed that the basic structure of salmonid TRB locus is a double set of two TRBV-D-J-C loci in opposite orientation on two different chromosomes. Our data shed light on the evolution of TRB loci in Salmonids after their whole genome duplication (WGD). We established a coherent nomenclature of salmonid TRB loci based on comprehensive annotation. Our work provides a fundamental basis for monitoring salmonid T cell responses by TRB repertoire sequencing.

    ano.nymous@ccsd.cnrs.fr.invalid (Pierre Boudinot) 11 Jul 2024

    https://hal.inrae.fr/hal-04280847v2
  • [inserm-04961151] Correlation Between Electronic Patient-Reported Outcomes and Biological Markers of Key Parameters in Acute Radiation Cystitis Among Patients With Prostate Cancer (RABBIO): Prospective Observational Study

    Background: Despite advances in radiation techniques, radiation cystitis (RC) remains a significant cause of morbidity from pelvic radiotherapy, which may affect patients' quality of life (QoL). The pathophysiology of RC is not well understood, which limits the development of effective treatments. Objective: The Radiotoxicity Bladder Biomarkers study aims to investigate the correlation between blood and urinary biomarkers and the intensity of acute RC symptoms and QoL in patients undergoing localized prostate cancer radiotherapy. Methods: This study included patients with low- or intermediate-risk localized prostate cancer who were eligible for localized radiotherapy. Blood and urinary biomarkers were analyzed before radiotherapy was initiated and at weeks 4 and 12 of radiation therapy. Patients completed questionnaires related to RC symptoms and QoL (International Prostate Symptom Score and Functional Assessment of Cancer Therapy-Prostate [FACT-P]) using a digital remote monitoring platform. The information was processed by means of an algorithm, which classified patients according to the severity of symptoms and adverse events reported. Levels of blood and urinary biomarkers were tested with the severity of acute RC symptoms and patient-reported QoL. Results: A total of 401 adverse events questionnaires were collected over the duration of this study from 20 patients. The most frequently reported adverse events at week 4 were pollakiuria, constipation, and diarrhea. In comparison with baseline, the mean FACT-P score decreased at week 4. A significant increase in the proportion of M2 phenotype cells (CD206+, CD163+, CD204+) at W12 compared to W0 was observed. An increase in serum and urine levels of macrophage colony-stimulating factor (M-CSF), hepatocyte growth factor, and macrophagic inflammatory protein was observed at week 12 compared to baseline levels. Baseline serum and urine M-CSF concentrations showed a significant negative correlation with FACT-P scores at weeks 4 and 12 (r=-0.65, P=.04, and r=-0.76, P=.02, respectively). Conclusions: The Radiotoxicity Bladder Biomarkers study is the first to explore the overexpression of inflammatory proteins in blood and urine of patients with symptoms of acute RC. These preliminary findings suggest that serum and urine levels of hepatocyte growth factor, M-CSF, and macrophagic inflammatory protein, as well as macrophage polarization, are mobilized after prostate radiotherapy. The elevated M-CSF levels in serum and urine at baseline were associated with the deterioration of QoL during radiotherapy. The results of this study may help to develop mitigation strategies to limit radiation damage to the bladder.

    ano.nymous@ccsd.cnrs.fr.invalid (Carole Helissey) 21 Feb 2025

    https://inserm.hal.science/inserm-04961151v1
  • [hal-05411391] Improving electrochemical aptasensor sensitivity for Bacillus cereus spore detection in food safety applications

    Rapid detection of Bacillus cereus spores is essential for preventing food contamination and spoilage. Many existing methods detect B. cereus vegetative cells rather than spores and cannot be applied directly to foods. Here, we present a combination of aptamers targeting different moieties on the surface of B. cereus spores with rapid electrochemical detection. When DNA aptamers, previously selected for B. cereus spores, were immobilized on screen-printed gold electrodes, they exhibited higher binding capacity than individual aptamers, suggesting a synergistic effect. Additionally, the mixture of rhodamine-labelled aptamers enabled spatial fluorescent visualization of the B. cereus endospore structure, confirming the increased binding efficiency. The electrochemical aptasensor based on three aptamers exhibited a wide dynamic range (102–107 CFU/mL) and low limit of detection (∼1 CFU/mL) using just 15 μL of sample. Validation in spiked salad, using direct spore sensing in rinse water and comparison with the culturing method, confirmed its sensitivity and specificity. These combined aptamer approaches, achieving rapid (15 min) and single-step detection may also be suitable for detecting other foodborne pathogens.

    ano.nymous@ccsd.cnrs.fr.invalid (Milica Sentic) 11 Dec 2025

    https://hal.science/hal-05411391v1
  • [hal-02948912] Workability tests on fresh concrete formulated with eco-friendly admixture

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    ano.nymous@ccsd.cnrs.fr.invalid (Nicolas Serres) 25 Sep 2020

    https://hal.science/hal-02948912v1
  • [hal-02949261] Bioréceptivité des matériaux cimentaires - protocole de préparation et analyses des surfaces en fonction du temps

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    ano.nymous@ccsd.cnrs.fr.invalid (Charlotte Munzer) 25 Sep 2020

    https://hal.science/hal-02949261v1
  • [hal-02625648] Colon Immune-Related Adverse Events: Anti-CTLA-4 and Anti-PD-1 Blockade Induce Distinct Immunopathological Entities

    Background and Aim: Immune checkpoint inhibitors targeting CTLA-4 and PD-1 improve survival in cancer patients but may induce immune-related adverse events, including colitis. The immunological characteristics of anti-CTLA-4 [alpha CTLA-4]- and anti-PD-1 [alpha PD-1]-related colitis have been poorly described. The aim of the present study was to compare the immunological and histological characteristics of alpha CTLA-4-induced colitis and alpha PD-1-induced colitis. Methods: Colonic biopsies from patients with alpha CTLA-4-induced colitis, alpha PD-1-induced colitis, and inflammatory bowel disease [IBD] were analysed by immunohistochemistry and flow cytometry. Tumour necrosis factor alpha [TNF alpha] concentration was assessed in biopsy supernatants. Results: CD8(+) T cells were found in the lamina propria and epithelium in alpha PD-1-induced colitis, whereas CD4(+) T cells were found in the lamina propria in alpha CTLA-4-induced colitis. No or low intraepithelial lymphocytes were observed in alpha CTLA-4-induced colitis. No difference in numbers of mucosal regulatory T cells was observed between alpha CTLA-4- or alpha PD-1-induced colitis and IBD patients. Higher numbers of activated ICOS+ conventional CD4(+) T cells were observed in alpha CTLA-4- induced colitis compared with patients with IBD. Among ICOS+ CD4(+) T cells, conventional CD4(+) T cells were the main T cell population in patents with alpha CTLA-4-induced colitis, whereas Treg cells were predominant in IBD or alpha PD-1-induced colitis. High mucosal TNF alpha concentrations were observed in alpha CTLA-4-induced colitis. Low mucosal TNF alpha concentrations were associated with steroid sensitivity. Conclusions: These observations show that alpha CTLA-4- and alpha PD-1-induced colitis have distinct immunological characteristics. Mucosal TNF alpha concentration might detect patients at risk of developing corticosteroid resistance after CTLA-4 blockade.

    ano.nymous@ccsd.cnrs.fr.invalid (Clelia Coutzac) 26 May 2020

    https://hal.inrae.fr/hal-02625648v1
  • [hal-03109210] Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer

    Gut microbiota composition influences the clinical benefit of immune checkpoints in patients with advanced cancer but mechanisms underlying this relationship remain unclear. Molecular mechanism whereby gut microbiota influences immune responses is mainly assigned to gut microbial metabolites. Short-chain fatty acids (SCFA) are produced in large amounts in the colon through bacterial fermentation of dietary fiber. We evaluate in mice and in patients treated with anti-CTLA-4 blocking mAbs whether SCFA levels is related to clinical outcome. High blood butyrate and propionate levels are associated with resistance to CTLA-4 blockade and higher proportion of Treg cells. In mice, butyrate restrains anti-CTLA-4-induced up-regulation of CD80/CD86 on dendritic cells and ICOS on T cells, accumulation of tumor-specific T cells and memory T cells. In patients, high blood butyrate levels moderate ipilimumab-induced accumulation of memory and ICOS + CD4 + T cells and IL-2 impregnation. Altogether, these results suggest that SCFA limits anti-CTLA-4 activity.

    ano.nymous@ccsd.cnrs.fr.invalid (Clélia Coutzac) 07 Jun 2023

    https://hal.science/hal-03109210v1
  • [hal-01604339] Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab

    Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity. Twenty-six patients with metastatic melanoma treated with ipilimumab were prospectively enrolled. Fecal microbiota composition was assessed using 16S rRNA gene sequencing at baseline and before each ipilimumab infusion. Patients were further clustered based on microbiota patterns. Peripheral blood lymphocytes immunophenotypes were studied in parallel. A distinct baseline gut microbiota composition was associated with both clinical response and colitis. Compared to patients whose baseline microbiota was driven by Bacteroides (Cluster B, n =10), patients whose baseline microbiota was enriched with Faecalibacterium genus and other Firmicutes (Cluster A, n =12) had longer progression-free survival ( p =0.0039) and overall survival ( p =0.051). Most of the baseline colitis-associated phylotypes were related to Firmicutes (e.g., relatives of Faecalibacterium prausnitzii and Gemmiger formicilis ), whereas no colitis-related phylotypes were assigned to Bacteroidetes. A low proportion of peripheral blood regulatory T cells was associated with Cluster A, long-term clinical benefit and colitis. Ipilimumab led to a higher Inducible T-cell COStimulator induction on CD4+ T cells and to a higher increase in serum CD25 in patients who belonged to Faecalibacterium -driven Cluster A. Baseline gut microbiota enriched with Faecalibacterium and other Firmicutes is associated with beneficial clinical response to ipilimumab and more frequent occurrence of ipilimumab-induced colitis.

    ano.nymous@ccsd.cnrs.fr.invalid (Nathalie Chaput) 02 Oct 2017

    https://hal.science/hal-01604339v1
  • [hal-01607061] Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?

    Checkpoint inhibitors blocking CTLA-4 (ipilimumab) and PD-1 (nivolumab, pembrolizumab) have transfigured our cancer treatment paradigm. However, these drugs can induce immune-related adverse events that share clinical and pathological characteristics with immune-mediated diseases. One of the most severe immune-related adverse event observed with anti-CTLA-4 is an enterocolitis that mirrors naturally occurring inflammatory bowel disease. This paper reviews the clinical, immunological, and microbiota data associated with the immune-related enterocolitis induced by the cancer immunotherapy blocking CTLA-4, ipilimumab. A parallel analysis of the mechanisms underlying inflammatory bowel diseases on the one hand, and anti-CTLA-4-induced colitis on the other hand, stresses the crucial role of the gut microbiota and of resident T-reg in the genesis of both iatrogenic and spontaneous inflammatory bowel diseases.

    ano.nymous@ccsd.cnrs.fr.invalid (Franck Carbonnel) 03 Oct 2017

    https://hal.science/hal-01607061v1
  • [pasteur-02554241] High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

    Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum-which is usually described as free of bacteria-became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ-deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.

    ano.nymous@ccsd.cnrs.fr.invalid (Julie Tomas) 28 May 2020

    https://pasteur.hal.science/pasteur-02554241v1
  • [hal-03786864] Cyclic di-AMP Oversight of Counter-Ion Osmolyte Pools Impacts Intrinsic Cefuroxime Resistance in Lactococcus lactis

    The broadly conserved cyclic di-AMP (c-di-AMP) is a conditionally essential bacterial second messenger. The pool of c-di-AMP is fine-tuned through diadenylate cyclase and phosphodiesterase activities, and direct binding of c-di-AMP to proteins and riboswitches allows the regulation of a broad spectrum of cellular processes. c-di-AMP has a significant impact on intrinsic b-lactam antibiotic resistance in Gram-positive bacteria; however, the reason for this is currently unclear. In this work, genetic studiesrevealed that suppressor mutations that decrease the activity of the potassium (K1) importer KupB or the glutamine importer GlnPQ restore cefuroxime (CEF) resistance in diadenylate cyclase (cdaA) mutants of Lactococcus lactis. Metabolite analyses showed thatglutamine is imported by GlnPQ and then rapidly converted to glutamate, and GlnPQ mutations or c-di-AMP negatively affects the pools of the most abundant free amino acids (glutamate and aspartate) during growth. In a high-c-di-AMP mutant, GlnPQ activity could be increased by raising the internal K1 level through the overexpression of a c-di-AMP-insensitive KupB variant. These results demonstrate that c-di-AMP reduces GlnPQ activity and, therefore, the level of the major free anions in L. lactis through its inhibition of K1 import. Excessive ion accumulation in cdaA mutants results in greater spontaneous cell lysis under hypotonic conditions, while CEF-resistant suppressors exhibit reduced cell lysis and lower osmoresistance. This work demonstrates that the overaccumulation of major counter-ion osmolyte pools in c-di-AMP-defective mutants of L. lactis causes cefuroxime sensitivity.

    ano.nymous@ccsd.cnrs.fr.invalid (Huong Thi Pham) 10 Sep 2024

    https://hal.inrae.fr/hal-03786864v1
  • [hal-01531770] Principles of Systems Biology, No. 11

    This month: AI that learns patterns and facts, new protein-RNA and protein-protein relationships, engineering signaling and metabolism, and more variants of Cas9.

    ano.nymous@ccsd.cnrs.fr.invalid (Greg Wayne) 01 Jun 2017

    https://hal.science/hal-01531770v1
  • [hal-05478791] Cobalamin-mediated protection of Faecalibacterium duncaniae against oxidative stress: Insights from proteomic and membrane fatty acid profiles

    Faecalibacterium species are keystone commensals of the human gut, contributing to intestinal homeostasis, immune modulation, and epithelial health. However, their extreme sensitivity to oxygen and reactive oxygen species renders them highly vulnerable during inflammatory conditions, severely limiting their therapeutic application. Understanding the molecular mechanisms underlying their oxidative stress responses is therefore critical for harnessing these bacteria as next-generation probiotics to restore gut health. In this study, we investigated oxidative stress responses in Faecalibacterium duncaniae A2–165 using comprehensive proteomic and membrane fatty acid profiling. We demonstrated that increasing hydrogen peroxide (H₂O₂) concentrations extend the lag phase of growth and affect survival during the first hour of exposure, notably altering the redox potential. Exposure to H₂O₂ triggered a remodeling of the proteome, including detoxification systems, metal transporters, DNA repair systems, transcriptional regulators, and enzymes involved in cobalamin biosynthesis. Complementary RT-qPCR analyses revealed coordinated and time-dependent transcriptional activation of genes involved in oxidative stress response. Remarkably, cobalamin supplementation enhanced bacterial growth, mitigated H₂O₂-induced stress, and lowered superoxide levels in F. duncaniae, highlighting its direct antioxidant activity. By analyzing membrane fatty acid profiles, we showed that cobalamin preserves membrane fluidity, counteracting oxidative stress induced by H₂O₂ in F. duncaniae. These findings reveal the multifaceted strategies employed by F. duncaniae to withstand oxidative stress and provide a foundation for future efforts to optimize its production at industrial scales and its therapeutic potential as a next-generation probiotic.

    ano.nymous@ccsd.cnrs.fr.invalid (Maria Alejandra de Angel Fontalvo) 27 Jan 2026

    https://institut-agro-dijon.hal.science/hal-05478791v1
  • [hal-04649763] MAIT cells monitor intestinal dysbiosis and contribute to host protection during colitis

    Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors and responds to such changes remains unclear. Here, we describe a protective mechanism by which mucosal-associated invariant T (MAIT) cells detect microbiota metabolites produced upon intestinal inflammation and promote tissue repair. At steady state, MAIT ligands derived from the riboflavin biosynthesis pathway were produced by aerotolerant bacteria residing in the colonic mucosa. Experimental colitis triggered luminal expansion of riboflavin-producing bacteria, leading to increased production of MAIT ligands. Modulation of intestinal oxygen levels suggested a role for oxygen in inducing MAIT ligand production. MAIT ligands produced in the colon rapidly crossed the intestinal barrier and activated MAIT cells, which expressed tissue-repair genes and produced barrier-promoting mediators during colitis. Mice lacking MAIT cells were more susceptible to colitis and colitis-driven colorectal cancer. Thus, MAIT cells are sensitive to a bacterial metabolic pathway indicative of intestinal inflammation.

    ano.nymous@ccsd.cnrs.fr.invalid (Yara El Morr) 10 Oct 2024

    https://hal.science/hal-04649763v1
  • [hal-03545788] Differentially optimized cell-free buffer enables robust expression from unprotected linear DNA in exonuclease-deficient extracts

    The use of linear DNA templates in cell-free systems promises to accelerate the prototyping and engineering of synthetic gene circuits. A key challenge is that linear templates are rapidly degraded by exonucleases present in cell extracts. Current approaches tackle the problem by adding exonuclease inhibitors and DNA-binding proteins to protect the linear DNA, requiring additional time-and resource-intensive steps. Here, we delete the recBCD exonuclease gene cluster from the Escherichia coli BL21 genome. We show that the resulting cell-free systems, with buffers optimized specifically for linear DNA, enable near-plasmid levels of expression from σ70 promoters in linear DNA templates without employing additional protection strategies. When using linear or plasmid DNA templates at the buffer calibration step, the optimal potassium glutamate concentrations obtained when using linear DNA were consistently lower than those obtained when using plasmid DNA for the same extract. We demonstrate the robustness of the exonuclease deficient extracts across seven different batches and a wide range of experimental conditions across two different laboratories. Finally, we illustrate the use of the ΔrecBCD extracts for two applications: toehold switch characterization and enzyme screening. Our work provides a simple, efficient, and cost-effective solution for using linear DNA templates in cell-free systems and highlights the importance of specifically tailoring buffer composition for the final experimental setup. Our data also suggest that similar exonuclease deletion strategies can be applied to other species suitable for cell-free synthetic biology.

    ano.nymous@ccsd.cnrs.fr.invalid (Angelo Cardoso Batista) 27 Jan 2022

    https://hal.inrae.fr/hal-03545788v1
  • [hal-05396365] NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner

    <div><p>Chronic obstructive pulmonary disease (COPD) is a major health issue primarily caused by cigarette smoke (CS) and characterized by breathlessness and repeated airway inflammation. NLRP6 is a cytosolic innate receptor controlling intestinal inflammation and orchestrating the colonic host-microbial interface. However, its roles in the lungs remain largely unexplored. Using CS exposure models, our data show that airway inflammation is strongly impaired in Nlrp6deficient mice with drastically fewer recruited neutrophils, a key cell subset in inflammation and COPD. We found that NLRP6 expression in lung epithelial cells is important to control airway and lung tissue inflammation in an inflammasomedependent manner. Since gut-derived metabolites regulate NLRP6 inflammasome activation in intestinal epithelial cells, we investigated the link between NLRP6, CS-driven lung inflammation, and gut microbiota composition. We report that acute CS exposure alters gut microbiota in both wild-type (WT) and Nlrp6-deficient mice and that antibiotic treatment decreases CS-induced lung inflammation. In addition, gut microbiota transfer from dysbiotic Nlrp6deficient mice to WT mice decreased airway lung inflammation in WT mice, h ighlighting an NLRP6-d epe nde nt gut-to-lu ng a xis co ntrolling pulmonary inflammation.</p></div>

    ano.nymous@ccsd.cnrs.fr.invalid (Mégane Nascimento) 03 Dec 2025

    https://hal.science/hal-05396365v1
  • [hal-05479927] Fructose malabsorption induces dysbiosis and increases anxiety in male human and animal models

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Adeline Coursan) 27 Jan 2026

    https://normandie-univ.hal.science/hal-05479927v1
  • [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
  • [hal-01204461] The detection of the methylated wif-1 gene is more accurate than a fecal occult blood test for colorectal cancer screening

    Background: The clinical benefit of guaiac fecal occult blood tests (FOBT) is now well established for colorectal cancer screening. Growing evidence has demonstrated that epigenetic modifications and fecal microbiota changes, also known as dysbiosis, are associated with CRC pathogenesis and might be used as surrogate markers of CRC. Patients and Methods: We performed a cross-sectional study that included all consecutive subjects that were referred (from 2003 to 2007) for screening colonoscopies. Prior to colonoscopy, effluents (fresh stools, sera-S and urine-U) were harvested and FOBTs performed. Methylation levels were measured in stools, S and U for 3 genes (Wif1, ALX-4, and Vimentin) selected from a panel of 63 genes; Kras mutations and seven dominant and subdominant bacterial populations in stools were quantified. Calibration was assessed with the Hosmer-Lemeshow chi-square, and discrimination was determined by calculating the C-statistic (Area Under Curve) and Net Reclassification Improvement index. Results: There were 247 individuals (mean age 60.8612.4 years, 52% of males) in the study group, and 90 (36%) of these individuals were patients with advanced polyps or invasive adenocarcinomas. A multivariate model adjusted for age and FOBT led to a C-statistic of 0.83 [0.77-0.88]. After supplementary sequential (one-by-one) adjustment, Wif-1 methylation (S or U) and fecal microbiota dysbiosis led to increases of the C-statistic to 0.90 [0.84-0.94] (p = 0.02) and 0.81 [0.74-0.86] (p = 0.49), respectively. When adjusted jointly for FOBT and Wif-1 methylation or fecal microbiota dysbiosis, the increase of the C-statistic was even more significant (0.91 and 0.85, p < 0.001 and p = 0.10, respectively). Conclusion: The detection of methylated Wif-1 in either S or U has a higher performance accuracy compared to guaiac FOBT for advanced colorectal neoplasia screening. Conversely, fecal microbiota dysbiosis detection was not more accurate. Blood and urine testing could be used in those individuals reluctant to undergo stool testing.

    ano.nymous@ccsd.cnrs.fr.invalid (Aurelien Amiot) 27 May 2020

    https://hal.science/hal-01204461v1
  • [pasteur-02551921] Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures

    Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls' microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.

    ano.nymous@ccsd.cnrs.fr.invalid (Iradj Sobhani) 05 May 2020

    https://pasteur.hal.science/pasteur-02551921v1
  • [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-04764173] Description, clinical impact and early outcome of S. maltophilia respiratory tract infections after lung transplantation, A retrospective observational study

    Background and research question S. maltophilia infections are associated with significant morbidity and mortality. Little is known regarding its presentation, management, and outcome in lung transplant recipients. Study design and Methods This retrospective case control study reviewed S. maltophilia respiratory tract infection in lung transplant recipients (01/01/2011-31/01/2020) and described the clinical, microbiological and outcome characteristics matched with lung transplant recipients without respiratory tract infection. Results and interpretation We identified 63 S. maltophilia infections in lung transplant recipients. Among them none were colonized before transplantation. Infections occurred a median of 177 (IQR: 45- 681) days post transplantation. Fifty-four (85.7 %) patients received trimethoprim-sulfamethoxazole (400/80 mg three times a week) to prevent Pneumocystis jirovecii pneumonia (PJP). S. maltophilia strains were susceptible to trimethoprim-sulfamethoxazole, levofloxacin, minocycline and ceftazidime in respectively 85.7 %, 82.5 %, 96.8 % and 34.9 % of cases. Median duration of treatment was 9 days (IQR 7–11.5). Clinical and microbiological recurrence were observed in respectively 25.3 % and 39.7 % of cases. Combination therapy was not associated with a decrease in the risk of recurrence and did not prevent the emergence of resistance. S. maltophilia respiratory tract infection was associated with a decline in FEV-1 at one year. Conclusion S. maltophilia is an important cause of lower respiratory tract infection in lung transplant recipients. Trimethoprim-sulfamethoxazole use as prophylaxis for PJP doesn't prevent S. maltophilia infection among lung transplant recipients. Levofloxacin and trimethoprim-sulfamethoxazole appear to be the two molecules of choice for the treatment of these infections and new antibiotic strategies (cefiderocol, aztreonam/avibactam) are currently being evaluated for multi-resistant S. maltophilia infections.

    ano.nymous@ccsd.cnrs.fr.invalid (Benoît Pilmis) 03 Nov 2024

    https://hal.inrae.fr/hal-04764173v1
  • [hal-05463746] Impact of Remdesivir on long-term outcomes in lung transplant recipients with SARS-CoV-2 infection: a retrospective cohort analysis

    The COVID-19 pandemic has presented considerable challenges for lung transplant (LTx) recipients, a population inherently at high risk for severe complications. Although early data from the pandemic indicated worrisome outcomes for these patients, understanding the current context of SARS-CoV-2 infections is essential to inform ongoing management strategies. The efficacy of anti-viral treatments, including Remdesivir (RDV), remains uncertain. This study aims to evaluate the effect of RDV on clinical outcomes in LTx recipients infected with SARS CoV-2, primarily those with a clinically significant disease course.

    ano.nymous@ccsd.cnrs.fr.invalid (Damiana-Maria Vulturar) 17 Jan 2026

    https://hal.science/hal-05463746v1
  • [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-03544230] Plastic biodegradation: Do Galleria mellonella Larvae Bioassimilate Polyethylene? A Spectral Histology Approach Using Isotopic Labeling and Infrared Microspectroscopy

    Environmental pollution by the nearly nonbiodegradable polyethylene (PE) plastics is of major concern; thus, organisms capable of biodegrading PE are required. The larvae of the Greater Wax Moth, Galleria mellonella (Gm), were identified as a potential candidate to digest PE. In this study, we tested whether PE was metabolized by Gm larvae and could be found in their tissues. We examined the implication of the larval gut microbiota by using conventional and axenic reared insects. First, our study showed that neither beeswax nor LDPE alone favor the growth of young larvae. We then used Fourier transform infrared microspectroscopy (μFTIR) to detect deuterium in larvae fed with isotopically labeled food. Deuterated molecules were found in tissues of larvae fed with deuterium labeled oil for 24 and 72 h, proving that μFTIR can detect metabolization of 1 to 2 mg of deuterated food. Then, Gm larvae were fed with deuterated PE (821 kDa). No bioassimilation was detected in the tissues of larvae that had ingested 1 to 5 mg of deuterated PE in 72 h or in 19 days, but micrometer sized PE particles were found in the larval digestive tract cavities. We evidenced weak biodegradation of 641 kDa PE films in contact for 24 h with the dissected gut of conventional larvae and in the PED4 particles from excreted larval frass. Our study confirms that Gm larvae can biodegrade HDPE but cannot necessarily metabolize it.

    ano.nymous@ccsd.cnrs.fr.invalid (Agnès Réjasse) 08 Dec 2023

    https://hal.inrae.fr/hal-03544230v1
  • [hal-03580568] PHROG: families of prokaryotic virus proteins clustered using remote homology

    Viruses are abundant, diverse and ancestral biological entities. Their diversity is high, both in terms of the number of different protein families encountered and in the sequence heterogeneity of each protein family. The recent increase in sequenced viral genomes constitutes a great opportunity to gain new insights into this diversity and consequently urges the development of annotation resources to help functional and comparative analysis. Here, we introduce PHROG (Prokaryotic Virus Remote Homologous Groups), a library of viral protein families generated using a new clustering approach based on remote homology detection by HMM profile-profile comparisons. Considering 17 473 reference (pro)viruses of prokaryotes, 868 340 of the total 938 864 proteins were grouped into 38 880 clusters that proved to be a 2-fold deeper clustering than using a classical strategy based on BLAST-like similarity searches, and yet to remain homogeneous. Manual inspection of similarities to various reference sequence databases led to the annotation of 5108 clusters (containing 50.6 % of the total protein dataset) with 705 different annotation terms, included in 9 functional categories, specifically designed for viruses. Hopefully, PHROG will be a useful tool to better annotate future prokaryotic viral sequences thus helping the scientific community to better understand the evolution and ecology of these entities.

    ano.nymous@ccsd.cnrs.fr.invalid (Paul Terzian) 18 Feb 2022

    https://hal.inrae.fr/hal-03580568v1
  • [hal-01536512] Regulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis

    We discovered a chromosomal locus containing 2 toxin-antitoxin modules (TAs) with an antisense transcriptional organization in the E. faecalis clinical isolate V583. These TAs are homologous to the type I txpA-ratA system and the type II mazEF, respectively. We have shown that the putative MazF is toxic for E. coli and triggers RNA degradation, and its cognate antitoxin MazE counteracts toxicity. The second module, adjacent to mazEF, expresses a toxin predicted to belong to the TxpA type I family found in Firmicutes, and the antisense RNA antidote, RatA. Genomic analysis indicates that the cis-association of mazEF and txpA-ratA modules has been favored during evolution, suggesting a selective advantage for this TA organization in the E. faecalis species. We showed regulatory interplays between the 2 modules, involving transcription control and RNA stability. Remarkably, our data reveal that MazE and MazEF have a dual transcriptional activity: they act as autorepressors and activate ratA transcription, most likely in a direct manner. RatA controls txpA RNA levels through stability. Our data suggest a pivotal role of MazEF in the coordinated expression of mazEF and txpA-ratA modules in V583. To our knowledge, this is the first report describing a crosstalk between type I and II TAs.

    ano.nymous@ccsd.cnrs.fr.invalid (Francoise Wessner) 04 Sep 2024

    https://hal.science/hal-01536512v1
  • [hal-02618779] Identification and characterization of EYK1, a key gene for erythritol catabolism in <em>Yarrowia lipolytica</em> (vol 101, pg 6587, 2017)

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (F. Carly) 25 May 2020

    https://hal.inrae.fr/hal-02618779v1
  • [hal-01001241] The lipases from Yarrowia lipolytica: genetics, production, regulation, biochemical characterization and biotechnological applications

    Lipases are serine hydrolases that catalyze in nature the hydrolysis of ester bonds of long chain triacylglycerol into fatty acid and glycerol. However, in favorable thermodynamic conditions, they are also able to catalyze reactions of synthesis such as esterification or amidation. The non-conventional yeast Yarrowia lipolytica possesses 16 paralogs of genes coding for lipase. However, little information on all those paralogs has been yet obtained and only three isoenzymes, namely Lip2p, Lip7p and Lip8p have been partly characterized so far. Microarray data suggest that only a few of them could be expressed and that lipase synthesis seems to be dependent on the fatty acid or oil used as carbon source confirming the high adaptation of Y. lipolytica to hydrophobic substrate utilization. This review focuses on the biochemical characterization of those enzymes with special emphasis on the Lip2p lipase which is the isoenzyme mainly synthesized by Y. lipolytica. Crystallographic data highlight that this latter is a lipase sensu stricto with a lid covering the active site of the enzyme in its closed conformation. Recent findings on enzyme conditioning in dehydrated or liquid formulation, in enzyme immobilization by entrapment in natural polymers from either organic or mineral origins are also discussed together with long-term storage strategies. The development of various biotechnological applications in different fields such as cheese ripening, waste treatment, drug synthesis or human therapeutics is also presented.

    ano.nymous@ccsd.cnrs.fr.invalid (Patrick P. Fickers) 04 Jun 2014

    https://hal.science/hal-01001241v1
  • [hal-02627658] Enhancing erythritol productivity in Yarrowia lipolytica using metabolic engineering

    Erythritol (1,2,3,4-butanetetrol) is a four-carbon sugar alcohol with sweetening properties that is used by the agrofood industry as a food additive. In this study, we demonstrated that metabolic engineering can be used to improve the production of erythritol from glycerol in the yeast Yarrowia lipolytica. The best results were obtained using a mutant that overexpressed GUT1 and TKL1, which encode a glycerol kinase and a transketolase, respectively, and in which EYK1, which encodes erythrulose kinase, was disrupted; the latter enzyme is involved in an early step of erythritol catabolism. In this strain, erythritol productivity was 75% higher than in the wild type; furthermore, the culturing time needed to achieve maximum concentration was reduced by 40%. An additional advantage is that the strain was unable to consume the erythritol it had created, further increasing the process's efficiency. The erythritol productivity values we obtained here are among the highest reported thus far.

    ano.nymous@ccsd.cnrs.fr.invalid (Frédéric Carly) 26 May 2020

    https://hal.inrae.fr/hal-02627658v1
  • [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
  • [hal-02623311] Identification and characterization of <em>EYD1</em>, encoding an erythritol dehydrogenase in <em>Yarrowia lipolytica</em> and its application to bioconvert erythritol into erythrulose

    In this study, gene YALI0F01650g has been isolated and characterized. Several experimental evidences suggest that the identified gene, renamed &lt;em&gt;EYD1&lt;/em&gt;, encodes an erythritol dehydrogenase. An efficient bioreactor process for the bioconversion of erythritol into erythrulose was also developed. Using constitutive expression of &lt;em&gt;EYD1&lt;/em&gt; in a &lt;em&gt;Y. lipolytica&lt;/em&gt; mutant containing a disrupted &lt;em&gt;EYK1&lt;/em&gt; gene, which encodes erythrulose kinase, erythrulose could be synthesized from erythritol at a rate of 0.116 g/g(DCW).h and with a bioconversion yield of 0.64 g/g.

    ano.nymous@ccsd.cnrs.fr.invalid (Frédéric Carly) 26 May 2020

    https://hal.inrae.fr/hal-02623311v1
  • [hal-02626429] New inducible promoter for gene expression and synthetic biology in <em>Yarrowia lipolytica</em>

    Background: The oleaginous yeast Yarrowia lipolytica is increasingly used as alternative cell factory for the production of recombinant proteins. At present, several promoters with different strengths have been developed based either on the constitutive pTEF promoter or on oleic acid inducible promoters such as pPOX2 and pLIP2. Although these promoters are highly efficient, there is still a lack of versatile inducible promoters for gene expression in &lt;em&gt;Y. lipolytica&lt;/em&gt;. Results: We have isolated and characterized the promoter of the EYK1 gene coding for an erythrulose kinase. pEYK1 induction was found to be impaired in media supplemented with glucose and glycerol, while the presence of erythritol and erythrulose strongly increased the promoter induction level. Promoter characterization and mutagenesis allowed the identification of the upstream activating sequence UAS1(EYK1). New hybrid promoters containing tandem repeats of either UAS1(XPR2) or UAS1(EYK1) were developed showing higher expression levels than the native pEYK1 promoter. Furthermore, promoter strength was improved in a strain carrying a deletion in the EYK1 gene, allowing thus the utilization of erythritol and erythrulose as free inducer. Conclusions: Novel tunable and regulated promoters with applications in the field of heterologous protein production, metabolic engineering, and synthetic biology have been developed, thus filling the gap of the absence of versatile inducible promoter in the yeast &lt;em&gt;Y. lipolytica&lt;/em&gt;.

    ano.nymous@ccsd.cnrs.fr.invalid (Marion Trassaert) 26 May 2020

    https://hal.inrae.fr/hal-02626429v1
  • [hal-02640216] Deciphering how LIP2 and POX2 promoters can optimally regulate recombinant protein production in the yeast Yarrowia lipolytica

    Background: In recent years, the non-conventional model yeast species Yarrowia lipolytica has received much attention because it is a useful cell factory for producing recombinant proteins. In this species, expression vectors involving LIP2 and POX2 promoters have been developed and used successfully for protein production at yields similar to or even higher than those of other cell factories, such as Pichia pastoris. However, production processes involving these promoters can be difficult to manage, especially if carried out at large scales in fed-batch bioreactors, because they require hydrophobic inducers, such as oleic acid or methyl oleate. Thus, the challenge has become to reduce loads of hydrophobic substrates while simultaneously promoting recombinant protein production. One possible solution is to replace a portion of the inducer with a co-substrate that can serve as an alternative energy source. However, implementing such an approach would require detailed knowledge of how carbon sources impact promoter regulation, which is surprisingly still lacking for the LIP2 and POX2 promoters. This study's aim was thus to better characterize promoter regulation and cell metabolism in Y. lipolytica cultures grown in media supplemented with different carbon sources. Results: pPOX2 induction could be detected when glucose or glycerol was used as sole carbon source, which meant these carbon source could not prevent promoter induction. In addition, when a mixture of glucose and oleic acid was used in complex medium, pPOX2 induction level was lower that that of pLIP2. In contrast, pLIP2 induction was absent when glucose was present in the culture medium, which meant that cell growth could occur without any recombinant gene expression. When a 40/60 mixture of glucose and oleic acid (w/w) was used, a tenfold increase in promoter induction, as compared to when an oleic-acid-only medium was observed. It was also clear that individual cells were adapting metabolically to use both glucose and oleic acid. Indeed, no distinct subpopulations that specialized on glucose versus oleic acid were observed; such an outcome would have led to producer and non-producer phenotypes. In medium containing both glucose and oleic acid, cells tended to directly metabolize oleic acid instead of storing it in lipid bodies. Conclusions: This study found that pLIP2 is a promoter of choice as compared to pPOX2 to drive gene expression for recombinant protein production by Y. lipolytica used as cell factory.

    ano.nymous@ccsd.cnrs.fr.invalid (Hosni Sassi) 28 May 2020

    https://hal.inrae.fr/hal-02640216v1
  • [hal-01535357] Genetic engineering of nonconventional yeasts for the production of valuable compounds

    Genetic engineering of nonconventional yeasts for the production of valuable compounds

    ano.nymous@ccsd.cnrs.fr.invalid (Andriy Sibirny) 08 Jun 2017

    https://hal.science/hal-01535357v1
  • [hal-02623203] Erratum to : Identification and characterization of <em>EYK1</em>, a key gene for erythritol catabolism in <em>Yarrowia lipolytica</em>

    Erythritol is a four-carbon sugar alcohol synthesized by osmophilic yeasts, such as Yarrowia lipolytica, in response to osmotic stress. This metabolite has application as food additive due to its sweetening properties. Although Y. lipolytica can produce erythritol at a high level from glycerol, it is also able to consume it as carbon source. This ability negatively affects erythritol productivity and represents a serious drawback for the development of an efficient erythritol production process. In this study, we have isolated by insertion mutagenesis a Y. lipolytica mutant unable to grow on erythritol. Genomic characterization of the latter highlighted that the mutant phenotype is directly related to the disruption of the YALI0F01606g gene. Several experimental evidences suggested that the identified gene, renamed EYK1, encodes an erythrulose kinase. The mutant strain showed an enhanced capacity to produce erythritol as compared to the wild-type strain. Moreover, in specific experimental conditions, it is also able to convert erythritol to erythrulose, another compound of biotechnological interest.

    ano.nymous@ccsd.cnrs.fr.invalid (F. Carly) 26 May 2020

    https://hal.inrae.fr/hal-02623203v1
  • [hal-02928505] The role of microbiota in tissue repair and regeneration

    A comprehensive understanding of the human body endogenous microbiota is essential for acquiring an insight into the involvement of microbiota in tissue healing and regeneration process in order to enable development of biomaterials with a better integration with human body environment. Biomaterials used for biomedical applications are normally germ-free, and the human body as the host of the biomaterials is not germ-free. The complexity and role of the body microbiota in tissue healing/regeneration have been underestimated historically. Traditionally, studies aiming at the development of novel biomaterials had focused on the effects of environment within the target tissue, neglecting the signals generated from the microbiota and their impact on tissue regeneration. The significance of the human body microbiota in relation to metabolism, immune system, and consequently tissue regeneration has been recently realised and is a growing research field. This review summarises recent findings on the role of microbiota and mechanisms involved in tissue healing and regeneration, in particular skin, liver, bone, and nervous system regrowth and regeneration highlighting the potential new roles of microbiota for development of a new generation of biomaterials.

    ano.nymous@ccsd.cnrs.fr.invalid (Amin Shavandi) 13 Feb 2024

    https://hal.inrae.fr/hal-02928505v1

Contact

micalis@inra.fr

Modification date: 26 January 2024 | Publication date: 12 April 2019 | By: RB