Search

We have determined whether orange juice-derived nanovesicles (ONVs) could be used for the treatment of obesity-associated intestinal complications. ONVs were characterized by lipidomic, metabolomic, electron microscopy. In vitro, intestinal barriers (IBs = Caco-2+HT-29-MTX) were treated with ONVs and co-cultured with adipocytes to monitor IB fat release. In vivo, obesity was induced with a high-fat, high-sucrose diet (HFHSD mice) for 12 weeks. Then, half of HFHSD mice were gavaged with ONVs. One-month ONV treatment did not modify HFHSD-induced insulin resistance but reversed diet-induced gut modifications. In the jejunum, ONVs increased villi size, reduced triglyceride content, and modulated mRNA levels of genes involved in immune response (tumor necrosis factor [TNF]-α and interleukin [IL]-1β), barrier permeability (CLDN1, OCLN, ZO1), fat absorption, and chylomicron release. ONVs targeted microsomal triglyceride transfer protein (MTP) and angiopoietin-like protein-4 (ANGPTL4), two therapeutic targets to reduce plasma lipids and inflammation in gastrointestinal diseases. Interestingly, ONV treatment did not aggravate liver steatosis, as MTP mRNA was increased in the liver. Therefore, ONVs protected both intestine and the liver from fat overload associated with the HFHSD. As ONVs concentrated amino acids and bioactive lipids versus orange juice, which are deficient in obese patients, the use of ONVs as a dietary supplement could bring physiological relevant compounds in the jejunum to accelerate the restoration of intestinal functions during weight loss in obese patients.

Urban Infiltration Basins (UIBs) are used to manage urban runoff transfers and feed aquifers. These UIBs can accumulate urban pollutants and favor the growth of potentially pathogenic biological agents as Nocardia. Objectives: To assess the spatio-temporal dynamics of pathogenic Nocardia in UIBs and to stablish phylogenetic relationships between clinical and UIB N. cyriacigeorgica strains. To assess pathogenicity associated with environmental N. cyriacigeorgica using an animal model, and to identify genetic elements that may be associated to its virulence. Methods: A well-characterized UIB in terms of chemical pollutants from Lyon area was used in this study during a whole year. Cultural and Next-Generation-Sequencing methods were used for Nocardia detection and typing. Clinical and environmental isolates phylogenetic relationships and virulences were compared with Multilocus-Sequence-Analysis study together with a murine model. Results: In autumn, N. cyriacigeorgica and N. nova were the pathogenic most prevalent species in the UIB. The complex N. abscessus/asiatica was also detected together with some other non-pathogenic species. The presence of pathogenic Nocardia was positively correlated to metallic trace elements. Up to 1.0 × 103 CFU/g sediment of N. cyriacigeorgica and 6 OTUs splited in two different phylogroups were retrieved and were close to clinical strains. The EML446 tested UIB isolate showed significant infectivity in mice with pulmonary damages similar to clinical clone (GUH-2). Conclusion: Hsp65 marker-based metabarcoding approach allowed detecting N. cyriacigeogica as the most abundant Nocardia pathogenic species in a UIB. Metal trace elements-polluted environments can be reservoirs of pathogenic Nocardia which may have a similar virulence to clinical strains.

Aim: Serum calprotectin (SC), a novel biomarker of inflammatory bowel diseases (IBD), has been recently investigated with conflicting results. The purpose of this study was to assess the ability of SC to predict relapse in IBD patients treated by biologic therapies, and to evaluate the correlation between SC, clinical and endoscopic relapse and other biomarkers as fecal calprotectin (FC) and C-reactive protein (CRP). Methods: All consecutive IBD patients in deep remission (clinical, endoscopic or imaging remission) were followed 12 months in this prospective study. Blood and stool samples were collected for SC, serum CRP and FC. SC was measured the day of inclusion (baseline, D0), 3 months (M3) and at 6 months (M6) or during the study period for clinical relapse. Relapse was defined as clinical, biomarkers, or endoscopic/imaging activities. Evolution of SC was quantified before relapse to analyze a predicting value of loss of response (LOR). SC for patients with active IBD and those with symptoms without inflammation were also compared. Results: Among the 119 patients included, 54 (46.4%) patients experienced a disease relapse during follow-up. Median SC levels did not increase in patients with clinical relapse (3.15 µg/ml at baseline, 3.38 µg/ml at M3, 3.33 µg/ml at M6 and 3.99 µg/ml in case of relapse (p = 0.63)). SC were compared during relapse in patients with endoscopic remission but clinical symptoms defined as secondary Irritable Bowel Syndrome (IBS). SC levels were higher in active IBD and similar between the groups of patients with IBS or deep remission (3.05 µg/ml IBS vs 2.99 µg/ml remission vs 5.1 µg/ml for clinical relapse, p = 0.04). In patients with clinical symptoms, SC presents a good predictive value for relapse (AUROC 0.764, IC95: 0.68–0.88), with a sensitivity of 72%, a specificity of 77%, using a cut-off value of 4.45 µg/ml. A weak, but significant correlation was found between SC and FC levels (r = 0.35, P = 0.001). A combined score with CRP, FC and SC is not efficient to improve IBD diagnostic. Conclusion: SC was significantly higher in patients with clinical relapse compared to those with endoscopic remission with or without clinical symptoms. SC allow to discriminate patients with active IBD or with IBS but failed to predict relapse.

Summary: Background: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. Methods: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. Findings: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. Interpretation: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. Funding: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.