105 results on '"Mondot S"'
Search Results
2. Structural robustness of the gut mucosal microbiota is associated with Crohnʼs disease remission after surgery
- Author
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Mondot, S, Lepage, P, Seksik, P, Allez, M, Tréton, X, Bouhnik, Y, Colombel, J F, Leclerc, M, Pochart, P, Doré, J, and Marteau, P
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- 2016
- Full Text
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3. Molecular investigation of bacterial communities on the inner and outer surfaces of peripheral venous catheters
- Author
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Zhang, L., Morrison, M., Nimmo, G. R., Sriprakash, K. S., Mondot, S., Gowardman, J. R., George, N., Marsh, N., and Rickard, C. M.
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- 2013
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4. Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept
- Author
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Amar, J., Serino, M., Lange, C., Chabo, C., Iacovoni, J., Mondot, S., Lepage, P., Klopp, C., Mariette, J., Bouchez, O., Perez, L., Courtney, M., Marre, M., Klopp, P., Lantieri, O., Doré, J., Charles, M. A., Balkau, B., Burcelin, R., and for the D.E.S.I.R. Study Group
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- 2011
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5. Saccharomyces cerevisiae, candida albicans and adherent-invasive escherichia coli (AIEC) intestinal colonization is not associated with asca detection in Crohn's disease
- Author
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Chevarin, Caroline, Mondot, S, Sarter, H., Cornu, Marjorie, SALEM, IMAN, RETUERTO, MAURICIO, Colombel, Jean Frédéric, Savoye, Guillaume, Ruemmele, Franck, Mosca, Alexis, Ley, Delphine, Desreumaux, Pierre, Borderon, Corinne, Beaugerie, Laurent, Buisson, Anthony, Collins, Michael, Ghannoum, Mahmoud, Lepage, Patricia, Barnich, Nicolas, Sendid, Boualem, Gower-Rousseau, Corinne, OUERTANI, jeannette, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
- Subjects
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2020
6. Associations entre profils metabolomiques plasmatiques rmn et composition du microbiote intestinal au sein d’une population d’adultes français en bonne santé
- Author
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Partula, V., primary, Mondot, S., additional, Torres, M., additional, Kesse-Guyot, E., additional, Lécuyer, L., additional, Deschasaux, M., additional, Assmann, K., additional, Latino-Martel, P., additional, Buscail, C., additional, Julia, C., additional, Galan, P., additional, Hercberg, S., additional, Victor-Bala, A., additional, Bouchemal, N., additional, Triba, M., additional, Savarin, P., additional, Rouilly, V., additional, Thomas, S., additional, Quintana-Murci, L., additional, Albert, M., additional, Lantz, O., additional, Duffy, D., additional, and Touvier, M., additional
- Published
- 2019
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7. Associations entre les consommations alimentaires et la composition du microbiote intestinal au sein d’une population d’adultes français en bonne santé
- Author
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Partula, V., primary, Mondot, S., additional, Torres, M., additional, Kesse-Guyot, E., additional, Deschasaux, M., additional, Latino-Martel, P., additional, Galan, P., additional, Hercberg, S., additional, Quintana-Murci, L., additional, Albert, M., additional, Duffy, D., additional, and Touvier, M., additional
- Published
- 2018
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8. EPS4.02 Porphyromonas, a candidate biomarker for detection of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis
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Guilloux, C.-A., primary, Marenne, G., additional, Mondot, S., additional, Lamoureux, C., additional, Billard, L., additional, Gouriou, S., additional, Vallet, S., additional, Le Berre, R., additional, Férec, C., additional, Génin, E., additional, and Héry-Arnaud, G., additional
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- 2018
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9. Groupes alimentaires et composition du microbiote intestinal chez des adultes français issus de la population générale : étude préliminaire
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Torres, M., primary, Mondot, S., additional, Kesse-Guyot, E., additional, Szabo-de-Edelenyi, F., additional, Latino-Martel, P., additional, and Galan, P., additional
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- 2017
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10. Complementarity and redundancy of IL-22-producing innate lymphoid cells
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Rankin, LC, Girard-Madoux, MJH, Seillet, C, Mielke, LA, Kerdiles, Y, Fenis, A, Wieduwild, E, Putoczki, T, Mondot, S, Lantz, O, Demon, D, Papenfuss, AT, Smyth, GK, Lamkanfi, M, Carotta, S, Renauld, J-C, Shi, W, Carpentier, S, Soos, T, Arendt, C, Ugolini, S, Huntington, ND, Bez, GT, Vivier, E, Rankin, LC, Girard-Madoux, MJH, Seillet, C, Mielke, LA, Kerdiles, Y, Fenis, A, Wieduwild, E, Putoczki, T, Mondot, S, Lantz, O, Demon, D, Papenfuss, AT, Smyth, GK, Lamkanfi, M, Carotta, S, Renauld, J-C, Shi, W, Carpentier, S, Soos, T, Arendt, C, Ugolini, S, Huntington, ND, Bez, GT, and Vivier, E
- Abstract
Intestinal T cells and group 3 innate lymphoid cells (ILC3 cells) control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet-dependent differentiation of NCR(-) ILC3 cells into NCR(+) ILC3 cells. Contrary to the prevailing view, we found by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR(+) ILC3 cells were redundant for the control of mouse colonic infection with Citrobacter rodentium in the presence of T cells. However, NCR(+) ILC3 cells were essential for cecal homeostasis. Our data show that interplay between intestinal ILC3 cells and adaptive lymphocytes results in robust complementary failsafe mechanisms that ensure gut homeostasis.
- Published
- 2016
11. ZAP-70 genotype disrupts the relationship between microbiota and host, leading to spondyloarthritis and ileitis in SKG mice
- Author
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Rehaume LM, Mondot S, Aguirre de Cárcer D, Velasco J, Benham H, Hasnain SZ, Bowman J, Ruutu M, Hansbro PM, McGuckin MA, Morrison M, and Thomas R
- Subjects
Mice, Knockout ,Mice, Inbred BALB C ,ZAP-70 Protein-Tyrosine Kinase ,Genotype ,Microbiota ,Ileitis ,Severity of Illness Index ,Interleukin-23 ,Arthritis & Rheumatology ,Toll-Like Receptor 4 ,Mice ,1103 Clinical Sciences, 1107 Immunology, 1117 Public Health and Health Services ,Spondylarthritis ,Animals ,Genetic Predisposition to Disease - Abstract
ObjectiveThe spondyloarthritides share genetic susceptibility, interleukin-23 (IL-23) dependence, and the involvement of microbiota. The aim of the current study was to elucidate how host genetics influence gut microbiota and the relationship between microbiota and organ inflammation in spondyloarthritides.MethodsBALB/c ZAP-70(W163C) -mutant (SKG) mice, Toll-like receptor 4 (TLR-4)-deficient SKG mice, and wild-type BALB/c mice were housed under specific pathogen-free conditions. SKG and wild-type BALB/c mice were maintained under germ-free conditions, and some of these mice were recolonized with altered Schaedler flora. All of the mice were injected intraperitoneally with microbial β-1,3-glucan (curdlan). Arthritis, spondylitis, and ileitis were assessed histologically. Microbiome composition was analyzed in serial fecal samples obtained from mice that were co-housed beginning at the time of weaning, using 454 pyrosequencing. Infiltrating cells and cytokines in the peritoneal cavity were measured by flow cytometry and enzyme-linked immunosorbent assay. Cytokine, endoplasmic reticulum (ER) stress marker, and tight junction protein transcription was measured by quantitative real-time polymerase chain reaction.ResultsMicrobiota content and response to curdlan varied according to whether T cell receptor signal strength was normal or was impaired due to the ZAP-70(W163C) mutation. Curdlan triggered acute inflammation regardless of the presence of the SKG allele or microbiota. However, no or limited microbiota content attenuated the severity of arthritis. In contrast, ileal IL-23 expression, ER stress, lymph node IL-17A production, goblet cell loss, and ileitis development were microbiota-dependent. Ileitis but not arthritis was suppressed by microbiota transfer upon co-housing SKG mice with wild-type BALB/c mice, as well as by TLR-4 deficiency.ConclusionThe interaction between immunogenetic background and host microbiota leads to an IL-23-dependent loss of mucosal function, triggering ileitis in response to curdlan.
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- 2014
12. Hypotensive activity of PAF-acether in rats
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Caillard, C. G., Mondot, S., Zundel, J. L., and Julou, L.
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- 1982
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13. Highlighting new phylogenetic specificities of Crohn’s disease microbiota
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Mondot, S., Kang, Seungha, Furet, J. P., Aguirre de Cárcer, Daniel, McSweeney, Christopher, Morrison, Mark, Marteau, Philippe, Doré, J., Leclerc, M., Mondot, S., Kang, Seungha, Furet, J. P., Aguirre de Cárcer, Daniel, McSweeney, Christopher, Morrison, Mark, Marteau, Philippe, Doré, J., and Leclerc, M.
- Abstract
microbes play a part in the pathogenesis of Crohn’s disease (CD). Methods: Fecal samples were collected from 16 healthy individuals and 16 CD patients (age- and sex-matched). The DNA extracted from these samples were subjected to two different methods of microbiome analysis. Specific bacterial groups were quantified by real-time polymerase chain reaction (PCR) methods using primers designed using a high-throughput in-house bioinformatics pipeline. The same DNA extracts were also used to produce fluorescently labeled cRNA amplicons to interrogate a custom-designed phylogenetic microarray for intestinal bacteria. Results: Even though the intersubject variability was high, differences in the fecal microbiomes of healthy and CD patients were detected. Faecalibacterium prausnitzii and Escherichia coli were more represented in healthy and ileal CD patients, respectively. Additionally, probes specific for Ruminococcus bromii, Oscillibacter valericigenes, Bifidobacterium bifidum, and Eubacterium rectale produced stronger hybridization signals with the DNA samples from healthy subjects. Conversely, species overrepresented in CD patients were E. coli, Enterococcus faecium, and species from the Proteobacteria not normally found in the healthy human GI tract. Furthermore, we detected ‘‘healthy specific’’ molecular species or operational taxonomic units (OTUs) that are not closely related to any known species (Faecalibacterium, Subdoligranulum, and Oscillospora species), indicating that the phylogenetic dysbiosis is broader than at strain or species level. Conclusions: These two techniques of microbiome analysis provided a statistically robust new picture of the dysbiosis in fecal microbiota from ileal CD patients. Specifically, we identified a set of six species discriminant for CD, which provides a preliminary diagnostic tool.
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- 2014
14. ANTI-ARRHYTHMIC ACTIVITIES OF 3-(2-HYDROXY-3-ISOPROPYLAMINO-PROPOXY)-2-PHENYL-1-ISOINDOLINONE, B FORM (R.P. 30 356)
- Author
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Detaille, J.Y., primary, Mondot, S., additional, Caillard, C.G., additional, and Julou, L., additional
- Published
- 1978
- Full Text
- View/download PDF
15. COMPARATIVE EFFECTS OF N-L LEUCYLDAUNORUBICINE (R.P. 20 132) AND DAUNORUBICINE ON ELECTROCAR-DIOGRAM OF THE RAT
- Author
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Mondot, S., primary, Caillard, C.G., additional, and Julou, L., additional
- Published
- 1978
- Full Text
- View/download PDF
16. Highlighting new phylogenetic specificities of Crohnʼs disease microbiota
- Author
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Mondot, S., primary, Kang, S., additional, Furet, J. P., additional, Aguirre de Carcer, D., additional, McSweeney, C., additional, Morrison, M., additional, Marteau, P., additional, Doré, J., additional, and Leclerc, M., additional
- Published
- 2011
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17. 2-(3-Pyridyl)-tetrahydrothiopyran-2-carbothioamide derivatives and analogues: A novel family of potent potassium channel openers
- Author
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Aloup, J.C., primary, Farge, D., additional, James, C., additional, Mondot, S., additional, and Cavero, I., additional
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- 1990
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18. Cardiovascular and biological effects of K+ channel openers, a class of drugs with vasorelaxant and cardioprotective properties
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Richer, C., primary, Pratz, J., additional, Mulder, P., additional, Mondot, S., additional, Giudicelli, J.F., additional, and Cavero, I., additional
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- 1990
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19. Vasorelaxant effects of cromakalim in rats are mediated by glibenclamide-sensitive potassium channels.
- Author
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Cavero, I, Mondot, S, and Mestre, M
- Abstract
Cromakalim (BRL 34915), a K+ channel activator, and diltiazem relaxed isolated rat aortic rings contracted with a low KCl concentration (25 mM). Gilbenclamide (0.1-3 microM) did not modify base-line resting tension or responses to KCl but prevented the vasorelaxant effects of cromakalim without affecting those of diltiazem or nitrendipine. Cromakalim, in contrast to the latter compounds, did not relax aortic rings contracted with 55 mM KCl. In pentobarbital-anesthetized rats prepared for hemodynamic measurements with Doppler flow probes, a 20-min i.v. infusion of cromakalim (5.0 micrograms/kg/min) lowered mean carotid artery blood pressure. This effect reached maximum after administration and was accompanied by decreases in systemic (35%), hindquarter (45%), mesenteric (27%), and renal (19%) vascular resistances. The blood pressure effects of cromakalim were not modified by BW 755C (lipo and cyclooxygenase inhibitor), idazoxan, methylatropine, methysergide, promethazine, propranolol, SCH 23390 (DA-1 receptor antagonist), S-sulpiride, RP 59227 (antagonist of platelet activating factor receptors) or by bilateral vagotomy associated with ligation of carotid arteries. However, in rats pretreated with the hypoglycemic sulfonylureas glibenclamide or glipizide (20 mg/kg i.v.), cromakalim, in contrast to diltiazem or dihydralazine, failed to produce hypotension. In rats deprived of sympathetic drive by pithing, cromakalim produced only a minor fall in blood pressure; however, this effect became pronounced when the low base-line blood pressure of this preparation was elevated by an i.v. infusion of vasopressin and could be prevented by glibenclamide. In conclusion, cromakalim posseses a novel mechanism of vasorelaxation that is consistent with the activation of a cellular outward K+ current.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1989
20. Effects of the K+ channel activators, RP 52891, cromakalim and diazoxide, on the plasma insulin level, plasma renin activity and blood pressure in rats.
- Author
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Pratz, J, Mondot, S, Montier, F, and Cavero, I
- Abstract
In normo- or hyperglycemic (i.v. infusion of 50 mg/kg/min glucose over 30 min) pithed rats, diazoxide (1 mg/kg/min i.v. over 20 min) significantly reduced plasma insulin content. By contrast, cromakalim, nicorandil or RP 52891 even at doses 40-fold higher than those producing the same hypotensive effect as diazoxide in intact anesthetized normotensive rats, failed to change insulin plasma levels. Glibenclamide (0.01-0.3 mg/kg i.v.) pretreatment antagonized dose-dependently the hypoinsulinemic activity of diazoxide with an i.v. ED50 value of 49 +/- 1 microgram/kg. In pithed rats, diazoxide increased markedly plasma renin activity. This effect was almost inhibited completely by 20 mg/kg i.v., but not at all by a 1-mg/kg i.v. dose of glibenclamide. In pentobarbital-anesthetized rats, diazoxide (0.5-2 mg/kg/min i.v. over 20 min) produced decreases in mean carotid artery blood pressure which were antagonized dose-dependently by glibenclamide (5-20 mg/kg i.v.). This sulfonylurea (20 mg/kg i.v.) also prevented the hypotensive effects of several i.v. administered K+ channel activators (cromakalim, RP 52891 and nicorandil) but not those of numerous hypotensive agents such as acetylcholine, adenosine, bradykinin, clonidine, histamine, salbutamol, dihydralazine, papaverine, platelet aggregating factor, nitroglycerin, nitroprusside, nitrendipine and diltiazem. Although glibenclamide lowered plasma glucose levels, its blocking activity vis-à-vis the hypotension evoked by cromakalim was not affected when its hypoglycemic effects were reversed with an i.v. injection of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
21. Hemodynamic and pharmacological evaluation of the vasodilator and vasoconstrictor effects of endothelin-1 in rats.
- Author
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Le Monnier de Gouville, A C, Mondot, S, Lippton, H, Hyman, A, and Cavero, I
- Abstract
In awake normotensive and spontaneously hypertensive rats as well as pentobarbital-anesthetized normotensive rats, endothelin-1 (ET-1, 0.063-0.5 nmol/kg i.v.) produced rapidly appearing, transient, dose-related falls in mean carotid artery blood pressure followed by slowly developing small pressor responses. In the latter preparation, the hypotension was due to a decrease in systemic vascular resistance inasmuch as cardiac output increased slightly. Bilateral vagotomy, BW 755c, glibenclamide, idazoxan, propranolol, methylatropine, methysergide or promethazine pretreatment failed to modify the hypotension induced by ET-1 (0.25 nmol/kg i.v.), but this effect was blocked entirely when ET-1 was injected 8 min after starting an i.v. infusion of ET-1 (0.1 nmol/kg/min for 10 min). In pithed rats, ET-1 (0.125-1.0 nmol/kg i.v.) produced sustained pressor responses which were accompanied by reductions in cardiac output. This peptide (0.25 nmol/kg i.v.) did not affect renal vascular resistance significantly but increased (200%) mesenteric resistance substantially more (3-fold) than systemic or hindquarter resistance. The pressor effects of ET-1 were reduced by diltiazem, nitrendipine, verapamil or cromakalim and unchanged after BW 755c, desipramine, enalapril, indomethacin, methysergide, phentolamine or SK&F 100273. The sustained pressor response evoked by an i.v. infusion of ET-1 (0.25 nmol/kg/min/60 min) was also antagonized markedly by nitrendipine and cromakalim. In pithed rats with vasopressin-supported blood pressure, ET-1 produced a short-lasting hypotension which faded entirely after three successive injections of the peptide. Finally, ET-1 (0.4-0.8 nM) evoked greater contractile responses in rat aortic rings deprived of a functional endothelium than in intact preparations. However, in the latter preparation precontracted with norepinephrine, ET-1, in contrast to acetylcholine, failed to evoke vasorelaxation. In aortic rings, the sustained contractile effects of ET-1 (3.2 nM) were reduced moderately by nitrendipine (50 nM) and markedly by cromakalim (0.8 microM). In contrast, the latter compounds antagonized strongly the contractile response to KCl (25 mM). In conclusion, ET-1 appears to produce active vasorelaxation and vasoconstriction via stimulation of specific receptors on blood vessels. The tolerance to the hypotensive effect of ET-1 may indicate that either the receptor site for ET-1 becomes refractory or, alternatively, it is coupled to easily depletable endogenous hypotensive mediators. Finally, inasmuch as the vasoconstrictor effects of ET-1 can be easily counteracted by calcium antagonists under in vivo but not in vitro conditions, the membrane coupling mechanism for ET-1 may not be exactly the same in conductance or resistance vessels.
- Published
- 1990
22. High affinity specific binding sites for tritiated platelet-activating factor in canine platelet membranes: counterparts of platelet-activating factor receptors mediating platelet aggregation.
- Author
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Tahraoui, L, Floch, A, Mondot, S, and Cavero, I
- Abstract
In canine platelet membranes, tritiated platelet activating factor (PAF) labels in a saturable and reversible manner a single population (nH = 0.97) of binding sites. The affinity of this binding was high (Kd = 0.23 +/- 0.02 nM, n = 4, and 0.21 +/- 0.05, n = 8, determined by kinetics or saturation experiments, respectively), and the density of binding sites (Bmax) was 911 +/- 31 fmol/mg of protein (n = 8). [3H]PAF binding was entirely reversed by unlabeled PAF (10 microM). [3H]PAF exhibited stereoselective discrimination inasmuch as it was poorly displaced by enantio-PAF, the PAF enantiomer that does not occur naturally. Furthermore, the displacing potency of the (+)-enantiomer of the PAF antagonist 52770 RP against [3H]PAF was 45 times higher than that of the (-)-enantiomer. [3H]PAF binding displayed a remarkable specificity in that it was not affected by a variety of classical pharmacological agents. However, this binding was displaced by several PAF receptor antagonists such as 59227 RP, CV-6209, Ro 19-3704, 52770 RP, brotizolam, WEB 2086, SRI 63-441, L-652,731, alprazolam, triazolam, and BN 52021. The Ki of the 16 studied antagonists ranged from 7.9 nM (59227 RP, most potent) to 16.8 microM (BN 52021, least potent). The possible biological significance of our binding procedure was assessed by correlating the potencies of 16 PAF antagonists as [3H]PAF displacers in dog platelet membranes and as inhibitors of PAF-induced platelet aggregation in washed canine platelets. This analysis revealed the existence of a highly significant correlation (r = 0.82, p less than 0.001) between biochemical and functional tests. However, two compounds (Ro 19-3704 and BN 52021) were found to be located outside the confidence limits when the probability level of belonging to the regression line was set at 0.01. In conclusion, this study provides evidence that [3H]PAF binding in canine platelet membranes exhibits the required properties for a valid binding procedure. Furthermore, the labeled sites are likely to be the counterparts of platelet receptors that, when activated by PAF, induce aggregation.
- Published
- 1988
23. Nicorandil: differential contribution of K+ channel opening and guanylate cyclase stimulation to its vasorelaxant effects on various endothelin-1-contracted arterial preparations. Comparison to aprikalim (RP 52891) and nitroglycerin.
- Author
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Borg, C, Mondot, S, Mestre, M, and Cavero, I
- Abstract
In endothelium-denuded rat aortic rings, the sustained contractile effects produced by endothelin-1 (ET-1; 3.2 nM) were concentration-dependently overcome by nicorandil, aprikalim (RP 52891), a specific K+ channel opener, and nitroglycerin, a stimulant of guanylate cyclase (EC50: 2.55 +/- 0.06, 0.37 +/- 0.05 and 0.3 +/- 0.008 microM respectively, n = 13-16/group). The decontractant activity of aprikalim was not affected by the guanylate cyclase inhibitor methylene blue (10 microM), whereas it was markedly antagonized by glibenclamide (1 microM) (pKB: 7.19 +/- 0.15), an antagonist of ATP-gated K+ channels in pancreatic beta cells. This sulfonylurea failed to modify nitroglycerin-induced effects, but slightly reduced (10-15%) those produced by high concentrations of nicorandil. By contrast, methylene blue significantly displaced (4-fold) the control concentration-vasorelaxant response curves obtained with nitroglycerin and nicorandil. Zaprinast (20 microM), an inhibitor of soluble low Km cyclic GMP phosphodiesterase, enhanced the effects of nitroglycerin and nicorandil but did not alter those of aprikalim. Nicorandil relaxed ET-1-contracted rings from micropig left circumflex coronary artery with an EC50 of 24 +/- 2.8 microM (n = 7); this effect was antagonized by methylene blue (10 microM) and glibenclamide (3 microM) (2- and 4-fold dextral shift of the control concentration-response curve, respectively). In rat Langendorff-perfused heart with base-line coronary flow reduced by the addition of ET-1 to the perfusion medium, nicorandil and aprikalim increased coronary flow, while nitroglycerin did not. The vasodilator effects of the two compounds were also inhibited by glibenclamide (pKB congruent to 7).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
24. Cardiovascular profile of 59227 RP, a novel potent and specific PAF receptor antagonists
- Author
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Mondot, S., primary and Cavero, I., additional
- Published
- 1988
- Full Text
- View/download PDF
25. Cardiovascular and biological effects of K + channel openers, a class of drugs with vasorelaxant and cardioprotective properties
- Author
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Richer, C., Pratz, J., Mulder, P., Mondot, S., Giudicelli, J.F., and Cavero, I.
- Published
- 1990
- Full Text
- View/download PDF
26. 171 - COMPARATIVE EFFECTS OF N-L LEUCYLDAUNORUBICINE (R.P. 20 132) AND DAUNORUBICINE ON ELECTROCAR-DIOGRAM OF THE RAT
- Author
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Mondot, S., Caillard, C.G., and Julou, L.
- Published
- 1978
- Full Text
- View/download PDF
27. 1112 - ANTI-ARRHYTHMIC ACTIVITIES OF 3-(2-HYDROXY-3-ISOPROPYLAMINO-PROPOXY)-2-PHENYL-1-ISOINDOLINONE, B FORM (R.P. 30 356)
- Author
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Detaille, J.Y., Mondot, S., Caillard, C.G., and Julou, L.
- Published
- 1978
- Full Text
- View/download PDF
28. MAIT cells monitor intestinal dysbiosis and contribute to host protection during colitis.
- Author
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El Morr Y, Fürstenheim M, Mestdagh M, Franciszkiewicz K, Salou M, Morvan C, Dupré T, Vorobev A, Jneid B, Premel V, Darbois A, Perrin L, Mondot S, Colombeau L, Bugaut H, du Halgouet A, Richon S, Procopio E, Maurin M, Philippe C, Rodriguez R, Lantz O, and Legoux F
- Subjects
- Animals, Mice, Mice, Knockout, Intestinal Mucosa immunology, Intestinal Mucosa microbiology, Riboflavin immunology, Mucosal-Associated Invariant T Cells immunology, Colitis immunology, Colitis microbiology, Dysbiosis immunology, Gastrointestinal Microbiome immunology, Mice, Inbred C57BL
- Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
29. A mechanistic modelling approach of the host-microbiota interactions to investigate beneficial symbiotic resilience in the human gut.
- Author
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Haghebaert M, Laroche B, Sala L, Mondot S, and Doré J
- Subjects
- Humans, Colon metabolism, Colon microbiology, Host Microbial Interactions physiology, Host Microbial Interactions immunology, Immunity, Innate, Gastrointestinal Microbiome physiology, Symbiosis physiology, Models, Biological
- Abstract
The health and well-being of a host are deeply influenced by the interactions with its gut microbiota. Contrasted environmental conditions, such as diseases or dietary habits, play a pivotal role in modulating these interactions, impacting microbiota composition and functionality. Such conditions can also lead to transitions from beneficial to detrimental symbiosis, viewed as alternative stable states of the host-microbiota dialogue. This article introduces a novel mathematical model exploring host-microbiota interactions, integrating dynamics of the colonic epithelial crypt, microbial metabolic functions, inflammation sensitivity and colon flows in a transverse section. The model considers metabolic shifts in epithelial cells based on butyrate and hydrogen sulfide concentrations, innate immune pattern recognition receptor activation, microbial oxygen tolerance and the impact of antimicrobial peptides on the microbiota. Using the model, we demonstrated that a high-protein, low-fibre diet exacerbates detrimental interactions and compromises beneficial symbiotic resilience, underscoring a destabilizing effect towards an unhealthy state. Moreover, the proposed model provides essential insights into oxygen levels, fibre and protein breakdown, and basic mechanisms of innate immunity in the colon and offers a crucial understanding of factors influencing the colon environment.
- Published
- 2024
- Full Text
- View/download PDF
30. Identification of the mechanism for dehalorespiration of monofluoroacetate in the phylum Synergistota.
- Author
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Leong LEX, Denman SE, Kang S, Mondot S, Hugenholtz P, and McSweeney CS
- Abstract
Objective: Monofluoroacetate (MFA) is a potent toxin that blocks ATP production via the Krebs cycle and causes acute toxicity in ruminants consuming MFA-containing plants. The rumen bacterium, Cloacibacillus porcorum strain MFA1 belongs to the phylum Synergistota and can produce fluoride and acetate from MFA as the end-products of dehalorespiration. The aim of this study was to identify the genomic basis for the metabolism of MFA by this bacterium., Methods: A draft genome sequence for C. porcorum strain MFA1 was assembled and quantitative transcriptomic analysis was performed thus highlighting a candidate operon encoding four proteins that are responsible for the carbon-fluorine bond cleavage. Comparative genome analysis of this operon was undertaken with three other species of closely related Synergistota bacteria., Results: Two of the genes in this operon are related to the substrate-binding components of the glycine reductase protein B (GrdB) complex. Glycine shares a similar structure to MFA suggesting a role for these proteins in binding MFA. The remaining two genes in the operon, an antiporter family protein and an oxidoreductase belonging to the radical S-adenosyl methionine superfamily, are hypothesised to transport and activate the GrdB-like protein respectively. Similar operons were identified in a small number of other Synergistota bacteria including type strains of Cloacibacillus porcorum, C. evryensis, and Pyramidobacter piscolens, suggesting lateral transfer of the operon as these genera belong to separate families. We confirmed that all three species can degrade MFA, however, substrate degradation in P. piscolens was notably reduced compared to Cloacibacillus isolates possibly reflecting the loss of the oxidoreductase and antiporter in the P. piscolens operon., Conclusion: Identification of this unusual anaerobic fluoroacetate metabolism extends the known substrates for dehalorespiration and indicates the potential for substrate plasticity in amino acid-reducing enzymes to include xenobiotics.
- Published
- 2024
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31. Multicenter evaluation of gut microbiome profiling by next-generation sequencing reveals major biases in partial-length metabarcoding approach.
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Roume H, Mondot S, Saliou A, Le Fresne-Languille S, and Doré J
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- Humans, Reproducibility of Results, High-Throughput Nucleotide Sequencing methods, DNA, Bacterial genetics, DNA, Bacterial analysis, RNA, Ribosomal, 16S genetics, Gastrointestinal Microbiome genetics, Microbiota genetics
- Abstract
Next-generation sequencing workflows, using either metabarcoding or metagenomic approaches, have massively contributed to expanding knowledge of the human gut microbiota, but methodological bias compromises reproducibility across studies. Where these biases have been quantified within several comparative analyses on their own, none have measured inter-laboratory reproducibility using similar DNA material. Here, we designed a multicenter study involving seven participating laboratories dedicated to partial- (P1 to P5), full-length (P6) metabarcoding, or metagenomic profiling (MGP) using DNA from a mock microbial community or extracted from 10 fecal samples collected at two time points from five donors. Fecal material was collected, and the DNA was extracted according to the IHMS protocols. The mock and isolated DNA were then provided to the participating laboratories for sequencing. Following sequencing analysis according to the laboratories' routine pipelines, relative taxonomic-count tables defined at the genus level were provided and analyzed. Large variations in alpha-diversity between laboratories, uncorrelated with sequencing depth, were detected among the profiles. Half of the genera identified by P1 were unique to this partner and two-thirds of the genera identified by MGP were not detected by P3. Analysis of beta-diversity revealed lower inter-individual variance than inter-laboratory variances. The taxonomic profiles of P5 and P6 were more similar to those of MGP than those obtained by P1, P2, P3, and P4. Reanalysis of the raw sequences obtained by partial-length metabarcoding profiling, using a single bioinformatic pipeline, harmonized the description of the bacterial profiles, which were more similar to each other, except for P3, and closer to the profiles obtained by MGP. This study highlights the major impact of the bioinformatics pipeline, and primarily the database used for taxonomic annotation. Laboratories need to benchmark and optimize their bioinformatic pipelines using standards to monitor their effectiveness in accurately detecting taxa present in gut microbiota., (© 2023. The Author(s).)
- Published
- 2023
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32. Impact of Oral Administration of Lactiplantibacillus plantarum Strain CNCM I-4459 on Obesity Induced by High-Fat Diet in Mice.
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Jacouton E, Mondot S, Langella P, and Bermúdez-Humarán LG
- Abstract
Recent evidence suggests that some lactobacilli strains, particularly Lactiplantibacillus plantarum , have a beneficial effect on obesity-associated syndromes. Several studies have investigated probiotic challenges in models of high-fat diet (HFD)-induced obesity, specifically with respect to its impact on hepatic and/or adipocyte metabolism, gut inflammation and epithelial barrier integrity, and microbiota composition. However, only a few studies have combined these aspects to generate a global understanding of how probiotics exert their protective effects. Here, we used the probiotic strain L. plantarum CNCM I-4459 and explored its impact on a mouse model of HFD-induced obesity. Briefly, mice were administered 1 × 10
9 CFUs/day and fed HFD for 12 weeks. Treatment with this strain improved insulin sensitivity by lowering serum levels of fasting glucose and fructosamine. Administration of the probiotic also affected the transport and metabolism of glucose, resulting in the downregulation of the hepatic Glut-4 and G6pase genes. Additionally, L. plantarum CNCM I-4459 promoted a decreased concentration of LDL-c and modulated hepatic lipid metabolism (downregulation of Fasn, Plin, and Cpt1α genes). Probiotic treatment also restored HFD-disrupted intestinal microbial composition by increasing microbial diversity and lowering the ratio of Firmicutes to Bacteroidetes. In conclusion, this probiotic strain represents a potential approach for at least partial restoration of the glucose sensitivity and lipid disruption that is associated with obesity.- Published
- 2023
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33. Evolution of T cell receptor beta loci in salmonids.
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Boudinot P, Novas S, Jouneau L, Mondot S, Lefranc MP, Grimholt U, and Magadán S
- Subjects
- Animals, Humans, Chromosomes, Human, Pair 19, Immunity, Cellular, Oncorhynchus mykiss genetics
- Abstract
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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Boudinot, Novas, Jouneau, Mondot, Lefranc, Grimholt and Magadán.)
- Published
- 2023
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34. From In Vitro to In Vivo: A Rational Flowchart for the Selection and Characterization of Candidate Probiotic Strains in Intestinal Disorders.
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Maillard F, Meynier M, Mondot S, Pepke F, Galbert C, Torres Maravilla E, Kropp C, Sokol H, Carvalho FA, Jacouton E, Holowacz S, Langella P, Chain F, and Martín R
- Abstract
Experimental and clinical evidence has demonstrated the potential of probiotic strains in the prevention or treatment of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). However, there is little data on what the methodology leading to the identification of such strains should be. In this work, we propose a new flowchart to identify strains with probiotic potential for the management of IBS and IBD, which we tested on a collection of 39 lactic acid bacteria and Bifidobacteria strains. This flowchart included in vitro tests of immunomodulatory properties on intestinal and peripheral blood mononuclear cells (PBMCs), assessment of the barrier-strengthening effect by measuring transepithelial electric resistance (TEER) and quantification of short-chain fatty acids (SCFAs) and aryl hydrocarbon receptor (AhR) agonists produced by the strains. The in vitro results were then combined in a principal component analysis (PCA) to identify strains associated with an anti-inflammatory profile. To validate our flowchart, we tested the two most promising strains identified in the PCA in mouse models of post-infectious IBS or chemically induced colitis to mimic IBD. Our results show that this screening strategy allows the identification of strains with potential beneficial effects on colonic inflammation and colonic hypersensitivity.
- Published
- 2023
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35. General transcription factor TAF4 antagonizes epigenetic silencing by Polycomb to maintain intestine stem cell functions.
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Säisä-Borreill S, Davidson G, Kleiber T, Thevenot A, Martin E, Mondot S, Blottière H, Helleux A, Mengus G, Plateroti M, Duluc I, Davidson I, and Freund JN
- Subjects
- Mice, Animals, Cell Differentiation genetics, Transcription Factor TFIID genetics, Intestinal Mucosa metabolism, Polycomb Repressive Complex 2 metabolism, Epigenesis, Genetic, Stem Cells metabolism, Drosophila Proteins metabolism
- Abstract
Taf4 (TATA-box binding protein-associated factor 4) is a subunit of the general transcription factor TFIID, a component of the RNA polymerase II pre-initiation complex that interacts with tissue-specific transcription factors to regulate gene expression. Properly regulated gene expression is particularly important in the intestinal epithelium that is constantly renewed from stem cells. Tissue-specific inactivation of Taf4 in murine intestinal epithelium during embryogenesis compromised gut morphogenesis and the emergence of adult-type stem cells. In adults, Taf4 loss impacted the stem cell compartment and associated Paneth cells in the stem cell niche, epithelial turnover and differentiation of mature cells, thus exacerbating the response to inflammatory challenge. Taf4 inactivation ex vivo in enteroids prevented budding formation and maintenance and caused broad chromatin remodeling and a strong reduction in the numbers of stem and progenitor cells with a concomitant increase in an undifferentiated cell population that displayed high activity of the Ezh2 and Suz12 components of Polycomb Repressive Complex 2 (PRC2). Treatment of Taf4-mutant enteroids with a specific Ezh2 inhibitor restored buddings, cell proliferation and the stem/progenitor compartment. Taf4 loss also led to increased PRC2 activity in cells of adult crypts associated with modification of the immune/inflammatory microenvironment that potentiated Apc-driven tumorigenesis. Our results reveal a novel function of Taf4 in antagonizing PRC2-mediated repression of the stem cell gene expression program to assure normal development, homeostasis, and immune-microenvironment of the intestinal epithelium., (© 2023. The Author(s).)
- Published
- 2023
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36. Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial.
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Pande A, Sharma S, Khillan V, Rastogi A, Arora V, Shasthry SM, Vijayaraghavan R, Jagdish R, Kumar M, Kumar G, Mondot S, Dore J, and Sarin SK
- Subjects
- Humans, Prednisolone therapeutic use, Fecal Microbiota Transplantation methods, Treatment Outcome, Hepatitis, Alcoholic drug therapy, Microbiota
- Abstract
Background: Severe alcoholic hepatitis (SAH) has high 90-day mortality. Prednisolone therapy has shown modest survival benefits over placebo at 28 but not 90 days. Fecal microbial transplantation (FMT) has shown promise in these patients. We compared the efficacy and safety of the two therapies in SAH patients., Methods: Steroid eligible SAH patients were randomized in an open-label study to prednisolone (n = 60) 40 mg/day for 28 days (assessed at day-7 for continuation) or healthy donor FMT (n = 60) through naso-duodenal tube, daily for seven days. Primary outcome of study was day-90 survival., Results: Patients in prednisolone and FMT arms were comparable at baseline (discriminant function score 65 ± 16.2 and 68 ± 14, MELD score 17.1 and 16.5, respectively). Of 120 patients, 112 [prednisolone-57; FMT-55] completed trial. As per intention-to-treat analysis, 90-day survival was achieved by 56.6% (34/60) patients in prednisolone and 75% (45/60) in FMT group (p = 0.044, FMT HR = 0.528, 95%CI 0.279-0.998). Secondary outcome of 28-day survival [78.33% (47/60) and 88.33% (53/60) (p = 0.243, FMT HR = 0.535, 95%CI 0.213-1.34)] with comparable severity scores over time between both arms. Infections accounted for 11 (19.3%) and 2 (3.6%) deaths in prednisolone and FMT groups, respectively (p = 0.01). Path-tracing showed a slow establishment of microbiota and alpha diversity (Shannon index) improvement by day-28 (p = 0.029). FMT resulted in 23 new taxa by day-28, reduction from baseline in pathogenic taxa [Campylobacter (19-fold, p = 0.035), anaerobes (Parcubacteria, Weisella and Leuconostocaceae)], and increase of Alphaproteobacteria [~ sevenfold, p = 0.047] and Thaumarcheota (known ammonia oxidizer, p = 0.06). Lachnospiraceae (p = 0.008), Prevotella and Viellonella communities in gut favored survival (p < 0.05)., Conclusion: In severe alcoholic hepatitis, FMT is safe and improves 90-day survival and reduces infections by favorably modulating microbial communities. It can be a useful alternative to prednisolone therapy., (© 2022. Asian Pacific Association for the Study of the Liver.)
- Published
- 2023
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37. Correlation Between Serum and Urine Biomarkers and the Intensity of Acute Radiation Cystitis in Patients Treated With Radiation Therapy for Localized Prostate Cancer: Protocol for the Radiotoxicity Bladder Biomarkers (RABBIO) Study.
- Author
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Helissey C, Cavallero S, Mondot S, Parnot C, Yssaad H, Becherirat S, Guitard N, Thery H, Schernberg A, Breitwiller H, Chargari C, and Francois S
- Abstract
Background: Despite improvements in radiation techniques, pelvic radiotherapy is responsible for acute and delayed bladder adverse events, defined as radiation cystitis. The initial symptoms of bladder injury secondary to pelvic irradiation are likely to occur during treatment or within 3 months of radiotherapy in approximately 50% of irradiated patients, and have a significant impact on their quality of life. The pathophysiology of radiation cystitis is not well understood, particularly because of the risk of complications associated with access to bladder tissue after irradiation, which limits our ability to study this process and develop treatments., Objective: It is an original study combining digital data collection to monitor patients' symptoms and biological markers during irradiation. The main objective of our study is to evaluate the correlation of biological biomarkers with the intensity of acute radiation cystitis and the quality of life of patients, assessed with the digital telemonitoring platform Cureety., Methods: Patients with intermediate-risk localized prostate cancer who are eligible for localized radiotherapy will be included. Inflammatory biomarkers will be analyzed in urine and blood samples before the start of radiotherapy and at weeks 4, 12, and 48 of irradiation, through quantitative methods such as a multiplex Luminex assay, flow cytometry, and enzyme-linked immunosorbent assay. We will also characterize the patients' gut and urine microbiota composition using 16S ribosomal RNA sequencing technology. Between sample collection visits, patients will complete various questionnaires related to radiation cystitis symptoms (using the International Prostate Symptom Score), adverse events, and quality of life (using the Functional Assessment of Cancer Therapy-Prostate questionnaire), using the Cureety digital remote monitoring platform. Upon receipt of the questionnaires, an algorithm will process the information and classify patients in accordance with the severity of symptoms and adverse events reported on the basis of Common Terminology Criteria for Adverse Events and International Prostate Symptom Score standards. This will allow us to correlate levels of urinary, blood, and fecal biomarkers with the severity of acute radiation cystitis symptoms and patient-reported quality of life., Results: The study started in March 2022. We estimate a recruitment period of approximately 18 months, and the final results are expected in 2024., Conclusions: This prospective study is the first to explore the overexpression of inflammatory proteins in fluid biopsies from patients with symptoms of acute radiation cystitis. In addition, the 1-year follow-up after treatment will allow us to predict which patients are at risk of late radiation cystitis and to refer them for radioprotective treatment. The results of this study will allow us to develop strategies to limit radiation damage to the bladder and improve the quality of life of patients., Trial Registration: ClinicalTrials.gov NCT05246774; https://clinicaltrials.gov/ct2/show/NCT05246774?term=NCT05246774., International Registered Report Identifier (irrid): DERR1-10.2196/38362., (©Carole Helissey, Sophie Cavallero, Stanislas Mondot, Charles Parnot, Halima Yssaad, Selma Becherirat, Nathalie Guitard, Hélène Thery, Antoine Schernberg, Hugo Breitwiller, Cyrus Chargari, Sabine Francois. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 10.01.2023.)
- Published
- 2023
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38. Roseburia, a decreased bacterial taxon in the gut microbiota of patients suffering from anorexia nervosa.
- Author
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Mondot S, Lachkar L, Doré J, Blottière HM, and Hanachi M
- Subjects
- Bacteria genetics, Cathartics, Feces microbiology, Humans, RNA, Ribosomal, 16S genetics, Anorexia Nervosa complications, Gastrointestinal Microbiome
- Abstract
Anorexia nervosa (AN) is a severe eating disorder which can lead to malnutrition and life threatening complications with high mortality rates. We designed our analysis to identify gut microbial taxa differentially abundant between AN and HC across different 16S rRNA gene datasets. We identified a reduced abundance, diversity and richness of Roseburia genus in the microbiota of patients with AN. Cares leading to partial recovery of patients with AN during hospitalization did not restore Roseburia to the levels of HC. AN dietary habit, either purgative or restrictive, did not affect Roseburia abundance. Roseburia genus and related species abundance were correlated with different health host metabolic markers. Roseburia species are key functional taxa in the human gut microbiome. Low gut Roseburia levels have been linked with other human pathologies. Our study highlights Roseburia species as a major decreased component in the gut of patients with AN., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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39. Long-Term Anxiety-like Behavior and Microbiota Changes Induced in Mice by Sublethal Doses of Acute Sarin Surrogate Exposure.
- Author
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François S, Mondot S, Gerard Q, Bel R, Knoertzer J, Berriche A, Cavallero S, Baati R, Orset C, Dal Bo G, and Thibault K
- Abstract
Anxiety disorder is one of the most reported complications following organophosphorus (OP) nerve agent (NA) exposure. The goal of this study was to characterize the long-term behavioral impact of a single low dose exposure to 4-nitrophenyl isopropyl methylphosphonate (NIMP), a sarin surrogate. We chose two different sublethal doses of NIMP, each corresponding to a fraction of the median lethal dose (one mild and one convulsive), and evaluated behavioral changes over a 6-month period following exposure. Mice exposed to both doses showed anxious behavior which persisted for six-months post-exposure. A longitudinal magnetic resonance imaging examination did not reveal any anatomical changes in the amygdala throughout the 6-month period. While no cholinesterase activity change or neuroinflammation could be observed at the latest timepoint in the amygdala of NIMP-exposed mice, important modifications in white blood cell counts were noted, reflecting a perturbation of the systemic immune system. Furthermore, intestinal inflammation and microbiota changes were observed at 6-months in NIMP-exposed animals regardless of the dose received. This is the first study to identify long-term behavioral impairment, systemic homeostasis disorganization and gut microbiota alterations following OP sublethal exposure. Our findings highlight the importance of long-term care for victims of NA exposure, even in asymptomatic cases.
- Published
- 2022
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40. Dynamic Properties of the Intestinal Ecosystem Call for Combination Therapies, Targeting Inflammation and Microbiota, in Ulcerative Colitis.
- Author
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van de Guchte M, Mondot S, and Doré J
- Subjects
- Anti-Inflammatory Agents adverse effects, Bacteria genetics, Bacteria immunology, Case-Control Studies, Colitis, Ulcerative immunology, Colitis, Ulcerative microbiology, Combined Modality Therapy, Dysbiosis, Host-Pathogen Interactions, Humans, Inflammation Mediators metabolism, Intestines metabolism, Intestines microbiology, Models, Biological, Remission Induction, Time Factors, Treatment Outcome, Anti-Inflammatory Agents therapeutic use, Bacteria drug effects, Cellular Microenvironment, Colitis, Ulcerative therapy, Fecal Microbiota Transplantation adverse effects, Gastrointestinal Microbiome drug effects, Immunity, Innate drug effects, Inflammation Mediators antagonists & inhibitors, Intestines drug effects
- Abstract
Background & Aims: Intestinal microbiota-host interactions play a major role in health and disease. This has been documented at the microbiota level ("dysbiosis" in chronic immune-mediated diseases) and through the study of specific bacteria-host interactions but rarely at the level of intestinal ecosystem dynamics. However, understanding the behavior of this ecosystem may be key to the successful treatment of disease. We recently postulated that health and disease represent alternative stable states of the intestinal ecosystem (different configurations that can exist under identical external conditions), which would require adapted strategies in disease treatment. Here, we examine if alternative stable states indeed exist in this ecosystem and if they could affect remission from ulcerative colitis (UC)., Methods: We analyzed data from a study on pediatric UC. The data reflect current treatment practice following the recruitment of treatment-naive patients with new-onset disease. Patients received personalized anti-inflammatory treatments over a period of 1 year. Stool samples at 0, 4, 12, and 52 weeks allowed an estimation of microbiota status (through 16S ribosomal RNA gene sequencing) and host inflammatory status (through the measurement of fecal calprotectin levels)., Results: We identify 4 microbiota states and 4 host states. Longitudinal data show that the improvement of inflammatory status is accompanied by an improvement of microbiota status. However, they also provide strong indications that both improvements are retarded or blocked by alternative states barriers., Conclusions: Our observations strongly suggest that inflammation suppression should be combined with microbiota management where possible to improve the efficacy of UC treatment., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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41. Impact of Antibiotic Therapies on Resistance Genes Dynamic and Composition of the Animal Gut Microbiota.
- Author
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Rochegüe T, Haenni M, Mondot S, Astruc C, Cazeau G, Ferry T, Madec JY, and Lupo A
- Abstract
Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of ARG s. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals' health status, with positive consequences on global health.
- Published
- 2021
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42. Profiling the T Cell Receptor Alpha/Delta Locus in Salmonids.
- Author
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Edholm ES, Fenton CG, Mondot S, Paulssen RH, Lefranc MP, Boudinot P, and Magadan S
- Subjects
- Amino Acid Sequence, Animals, Conserved Sequence, Gene Expression Profiling, Gene Library, Genome, Models, Molecular, Molecular Sequence Annotation, Oncorhynchus mykiss immunology, Phylogeny, Protein Conformation, RNA, Messenger genetics, Receptors, Antigen, T-Cell biosynthesis, Receptors, Antigen, T-Cell chemistry, Salmo salar immunology, Sequence Alignment, Sequence Homology, Amino Acid, Species Specificity, Terminology as Topic, Genes, T-Cell Receptor genetics, Oncorhynchus mykiss genetics, Receptors, Antigen, T-Cell genetics, Salmo salar genetics
- Abstract
In jawed vertebrates, two major T cell populations have been characterized. They are defined as α/β or γ/δ T cells, based on the expressed T cell receptor. Salmonids (family Salmonidae ) include two key teleost species for aquaculture, rainbow trout ( Oncorhynchus mykiss ) and Atlantic salmon ( Salmo salar) which constitute important models for fish immunology and important targets for vaccine development. The growing interest to decipher the dynamics of adaptive immune responses against pathogens or vaccines has resulted in recent efforts to sequence the immunoglobulin (IG) or antibodies and T cell receptor (TR) repertoire in these species. In this context, establishing a comprehensive and coherent locus annotation is the fundamental basis for the analysis of high-throughput repertoire sequencing data. We therefore decided to revisit the description and annotation of TRA/TRD locus in Atlantic salmon and two strains of rainbow trout (Swanson and Arlee) using the now available high-quality genome assemblies. Phylogenetic analysis of functional TRA/TRD V genes from these three genomes led to the definition of 25 subgroups shared by both species, some with particular feature. A total of 128 TRAJ genes were identified in Salmo , the majority with a close counterpart in Oncorhynchus . Analysis of expressed TRA repertoire indicates that most TRAV gene subgroups are expressed at mucosal and systemic level. The present work on TRA/TRD locus annotation along with the analysis of TRA repertoire sequencing data show the feasibility and advantages of a common salmonid TRA/TRD nomenclature that allows an accurate annotation and analysis of high-throughput sequencing results, across salmonid T cell subsets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Edholm, Fenton, Mondot, Paulssen, Lefranc, Boudinot and Magadan.)
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- 2021
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43. Associations between untargeted plasma metabolomic signatures and gut microbiota composition in the Milieu Intérieur population of healthy adults.
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Partula V, Deschasaux-Tanguy M, Mondot S, Victor-Bala A, Bouchemal N, Lécuyer L, Bobin-Dubigeon C, Torres MJ, Kesse-Guyot E, Charbit B, Patin E, Assmann KE, Latino-Martel P, Julia C, Galan P, Hercberg S, Quintana-Murci L, Albert ML, Duffy D, Lantz O, Savarin P, Triba MN, and Touvier M
- Subjects
- Adult, Creatinine, Feces, Humans, Metabolomics, Plasma chemistry, RNA, Ribosomal, 16S genetics, Gastrointestinal Microbiome, Metabolome
- Abstract
Host-microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host-microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton NMR analysis of plasma. The associations between metabolomic variables and α- and β-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini-Hochberg, 10 % false discovery rate). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose and citrate (-0·133 ≤ Spearman's ρ ≤ 0·126). Specific associations between metabolomic signals and abundances of taxa were detected (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven species and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host-gut microbiota metabolic relationships. In particular, our results support the implication of a 'gut-kidney axis'. More studies providing a detailed exploration of these complex interactions and their implications for host health are needed.
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- 2021
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44. Parasites and diet as main drivers of the Malagasy gut microbiome richness and function.
- Author
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Mondot S, Poirier P, Abou-Bacar A, Greigert V, Brunet J, Nourrisson C, Randrianarivelojosia M, Razafindrakoto JL, Morel E, Rakotomalala RS, Leclerc M, Le Roux K, Monot C, Lepage P, and Candolfi E
- Subjects
- Adult, Animals, Feeding Behavior, Female, Humans, Madagascar, Male, Metabolomics, Diet, Feces microbiology, Gastrointestinal Microbiome physiology, Parasites isolation & purification
- Abstract
Interactions between the prokaryotic microbiome and eukaryotic parasites in the vertebrate gut may affect overall host health and disease. While intertropical areas exhibit a high rate of parasites carriers, such interactions are understudied in these populations. Our objectives were to (1) describe the gut microbiome of individuals living in Madagascar, (2) identify potential associations between bacterial taxa and parasites colonizing the digestive tract and (3) highlight main determinants of the gut microbiota composition in this developing country. Metadata (socioeconomic, diet, clinical) and fecal samples were collected from 219 volunteers from North-West Madagascar (Mahajanga). Fecal microbiome was assessed through 16S rRNA gene sequencing and metabolomics, and related to dietary habits and parasites carriage. We highlight important Malagasy gut microbiome peculiarities. Out of three detected enterotypes, only one is similar to that observed in Westernized countries (Ruminococcus-driven). Functions associated with the two others (Clostridium sensu stricto-driven and Escherichia/Shigella-driven) are mostly directed toward amino acids biosynthesis and degradation, respectively. Diet and protozoan carriage were the main drivers of microbiota composition. High protozoan carriage was associated with higher diversity, richness and microbial functionalities. The gut microbiome of Malagasy strongly differs from that of Westernized countries. Asymptomatic protozoan carriage and dietary habits are the external factors with the deepest impact on gut microbiome. Further studies are needed to understand whether gut microbial richness constitute a predilection niche for protozoans colonization, due to their gazing features, or whether the parasites themselves induce a higher bacterial richness., (© 2021. The Author(s).)
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- 2021
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45. Genomic analysis of a second rainbow trout line (Arlee) leads to an extended description of the IGH VDJ gene repertoire.
- Author
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Magadan S, Mondot S, Palti Y, Gao G, Lefranc MP, and Boudinot P
- Subjects
- Animals, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Oncorhynchus mykiss immunology, Phylogeny, Genes, Immunoglobulin Heavy Chain genetics, Oncorhynchus mykiss genetics, V(D)J Recombination immunology
- Abstract
High-throughput sequencing technologies brought a renewed interest for immune repertoires. Fish Ab and B cell repertoires are no exception, and their comprehensive analysis can both provide new insights into poorly understood immune mechanisms, and identify markers of protection after vaccination. However, the lack of genomic description and standardized nomenclature of IG genes hampers accurate annotation of Ig mRNA deep sequencing data. Complete genome sequences of Atlantic salmon and rainbow trout (Swanson line) recently allowed us to establish a comprehensive and coherent annotation of Salmonid IGH genes following IMGT standards. Here we analyzed the IGHV, D, and J genes from the newly released genome of a second rainbow trout line (Arlee). We confirmed the validity of salmonid IGHV subgroups, and extended the description of the rainbow trout IGH gene repertoire with novel sequences, while keeping nomenclature continuity. This work provides an important resource for annotation of high-throughput Ab repertoire sequencing data., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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46. Anorexia nervosa and gut microbiota: A systematic review and quantitative synthesis of pooled microbiological data.
- Author
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Di Lodovico L, Mondot S, Doré J, Mack I, Hanachi M, and Gorwood P
- Subjects
- Anorexia Nervosa diagnosis, Humans, Anorexia Nervosa metabolism, Anorexia Nervosa microbiology, Brain-Gut Axis physiology, Data Analysis, Gastrointestinal Microbiome physiology, Microbiological Phenomena
- Abstract
Background: Alterations of gut microbiota may play a role in Anorexia Nervosa (AN) through perturbations of the gut-brain axis. Some studies found differences in the gut microbiota of patients with AN compared to healthy controls, but results are heterogeneous. The aim of this work was to systematically review the existing studies comparing gut microbial composition in AN and healthy controls, and to perform a quantitative synthesis of the pooled clinical and microbiological data, when available., Methods: A comprehensive literature search was performed to identify human studies investigating relationships between AN and gut microbiota. Microbiome datasets from studies were pooled and analysed focusing on alpha and beta-diversity and the relative abundance of microbial species in patients' gut microbiota compared to healthy controls., Results: Nine studies were eligible for the systematic review, of which 4 were included in the quantitative synthesis. Preserved alpha-diversity and decreased beta-diversity in AN emerged from the qualitative synthesis, while a slight increase of alpha-diversity (d < 0.4) and comparable beta-diversity were reported by the quantitative synthesis. Out of the 46 common species compared, three had a large combined effect size (d ≥ 0.9) to differentiate patients from controls, namely Alistipes, Parabacterioides and Roseburia. The latter was also correlated with BMI (ρ = 0.29)., Conclusions: The decrease of butyrate-producing species and the increase of mucine-degrading species may represent hallmarks of the gut microbiota alterations in AN, and therefore potentially interesting therapeutic targets. The heterogeneity of clinical and methodological characteristics hampers the generalizability of the results. Standardized research methods could improve comparability among studies to better identify the alterations of gut microbiota in AN., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2021
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47. Alternative stable states in the intestinal ecosystem: proof of concept in a rat model and a perspective of therapeutic implications.
- Author
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Van de Guchte M, Burz SD, Cadiou J, Wu J, Mondot S, Blottière HM, and Doré J
- Subjects
- Animals, Dextran Sulfate pharmacology, Inflammation chemically induced, Inflammation microbiology, Intestines drug effects, Intestines pathology, Male, RNA, Ribosomal, 16S genetics, Rats, Gastrointestinal Microbiome drug effects, Gastrointestinal Microbiome genetics, Intestines microbiology
- Abstract
Background: Chronic immune-mediated diseases are rapidly expanding and notoriously difficult to cure. Altered relatively stable intestinal microbiota configurations are associated with several of these diseases, and with a possible pre-disease condition (more susceptible to disease development) of the host-microbiota ecosystem. These observations are reminiscent of the behavior of an ecosystem with alternative stable states (different stable configurations that can exist under identical external conditions), and we recently postulated that health, pre-disease and disease represent such alternative states. Here, our aim was to examine if alternative stable states indeed exist in the intestinal ecosystem., Results: Rats were exposed to varying concentrations of DSS in order to create a wide range of mildly inflammatory conditions, in a context of diet-induced low microbiota diversity. The consequences for the intestinal microbiota were traced by 16S rRNA gene profiling over time, and inflammation of the distal colon was evaluated at sacrifice, 45 days after the last DSS treatment. The results provide the first formal experimental proof for the existence of alternative stable states in the rat intestinal ecosystem, taking both microbiota and host inflammatory status into consideration. The alternative states are host-microbiota ecosystem states rather than independent and dissociated microbiota and host states, and inflammation can prompt stable state-transition. Based on these results, we propose a conceptual model providing new insights in the interplay between host inflammatory status and microbiota status. These new insights call for innovative therapeutic strategies to cure (pre-)disease., Conclusions: We provide proof of concept showing the existence of alternative stable states in the rat intestinal ecosystem. We further propose a model which, if validated in humans, will support innovative diagnosis, therapeutic strategy, and monitoring in the treatment of chronic inflammatory conditions. This model provides a strong rationale for the application of combinatorial therapeutic strategies, targeting host and microbiota rather than only one of the two in chronic immune-mediated diseases. Video Abstract.
- Published
- 2020
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48. Associations between consumption of dietary fibers and the risk of cardiovascular diseases, cancers, type 2 diabetes, and mortality in the prospective NutriNet-Santé cohort.
- Author
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Partula V, Deschasaux M, Druesne-Pecollo N, Latino-Martel P, Desmetz E, Chazelas E, Kesse-Guyot E, Julia C, Fezeu LK, Galan P, Hercberg S, Mondot S, Lantz O, Quintana-Murci L, Albert ML, Duffy D, Srour B, and Touvier M
- Subjects
- Adult, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 mortality, Dietary Fiber analysis, Female, Fruit chemistry, Fruit metabolism, Humans, Male, Middle Aged, Neoplasms mortality, Prospective Studies, Vegetables chemistry, Vegetables metabolism, Cardiovascular Diseases metabolism, Diabetes Mellitus, Type 2 metabolism, Dietary Fiber metabolism, Neoplasms metabolism
- Abstract
Background: Mounting evidence, yet with varying levels of proof, suggests that dietary fibers (DFs) may exert a protective role against various chronic diseases, but this might depend on the DF type and source., Objectives: Our objectives were to assess the associations between the intake of DFs of different types [total (TDF), soluble (SF), insoluble (IF)] and from different sources (fruits, vegetables, whole grains, legumes, potatoes and tubers) and the risk of cardiovascular diseases (CVDs), cancer, type 2 diabetes (T2D), and mortality in the large-scale NutriNet-Santé prospective cohort (2009-2019)., Methods: Overall, 107,377 participants were included. Usual DF intake was estimated from validated repeated 24-h dietary records over the first 2 y following inclusion in the cohort. Associations between sex-specific quintiles of DF intake and the risk of chronic diseases and mortality were assessed using multiadjusted Cox proportional hazards models., Results: T2D risk was inversely associated with TDFs [HR for quintile 5 compared with quintile 1: 0.59 (95% CI: 0.42, 0.82), P-trend <0.001], SFs [HR: 0.77 (0.56, 1.08); P-trend = 0.02], and IFs [HR: 0.69 (0.50, 0.96); P-trend = 0.004]. SFs were associated with a decreased risk of CVD [HR: 0.80 (0.66, 0.98); P-trend = 0.01] and colorectal cancer [HR: 0.41 (0.21, 0.79); P-trend = 0.01]. IFs were inversely associated with mortality from cancer or CVDs [HR: 0.65 (0.45, 0.94); P-trend = 0.02]. TDF intake was associated with a decreased risk of breast cancer [HR:: 0.79 (0.54, 1.13); P-trend = 0.04]. DF intake from fruit was associated with the risk of several chronic diseases., Conclusions: Our results suggest that DF intake, especially SFs and DFs from fruits, was inversely associated with the risk of several chronic diseases and with mortality. Further studies are needed, involving different types and sources of fiber. Meanwhile, more emphasis should be put on DFs in public health nutrition policies, as DF intake remains below the recommended levels in many countries. This trial was registered at clinicaltrials.gov as NCT03335644., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)
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- 2020
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49. The T cell receptor (TRA) locus in the rabbit (Oryctolagus cuniculus): Genomic features and consequences for invariant T cells.
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Mondot S, Lantz O, Lefranc MP, and Boudinot P
- Subjects
- Animals, Humans, Mice, Rabbits, Receptors, Antigen, T-Cell immunology, Genetic Loci, Immunity, Innate genetics, Natural Killer T-Cells, Receptors, Antigen, T-Cell genetics
- Abstract
The rabbit has been widely used in immunology and infectiology. Rabbit immunoglobulins have been extensively studied, leading to the discovery of their idiotypes, allotypic diversity, and of the diversification of the primary repertoire by hyperconversion. Much less is known about rabbit T cell receptors (TR), especially TRA. This isotype is particularly important for innate-like T cells, which typically express invariant TRA (iTRA). The presence of such cells in the rabbit remains an enigma. Rabbit NKT cells seem to be very rare, and lagomorphs lack MAIT cells. TRAV1, the variable gene expressed in the iTRA of these cells across most mammals, and MR1, the MH1-like receptor that present riboflavin derivatives to MAIT cells, are missing in rabbit. An alternative iTRA has been identified, that may be expressed by new innate-like T cells. To facilitate TRA repertoire analyses in rabbit, we report here a full description of TRA and TRD loci and a subgroup definition based on IMGT® classification. Rabbit TRA rearrangements follow the same temporal pattern that is observed in mouse and human. Rare transcripts expressing TRDV/TRDD/TRDJ rearrangements spliced to TRAC were detected. TRA and TRD genes have been made available in IMGT and IMGT/HighV-QUEST, allowing easy analysis of TRA/TRD RepSeq., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2019
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50. Standardized IMGT® Nomenclature of Salmonidae IGH Genes, the Paradigm of Atlantic Salmon and Rainbow Trout: From Genomics to Repertoires.
- Author
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Magadan S, Krasnov A, Hadi-Saljoqi S, Afanasyev S, Mondot S, Lallias D, Castro R, Salinas I, Sunyer O, Hansen J, Koop BF, Lefranc MP, and Boudinot P
- Subjects
- Animals, Computational Biology, Gene Expression Regulation, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, Phylogeny, V(D)J Recombination, Genes, Immunoglobulin Heavy Chain, Molecular Sequence Annotation methods, Oncorhynchus mykiss genetics, Salmo salar genetics
- Abstract
In teleost fish as in mammals, humoral adaptive immunity is based on B lymphocytes expressing highly diverse immunoglobulins (IG). During B cell differentiation, IG loci are subjected to genomic rearrangements of V, D, and J genes, producing a unique antigen receptor expressed on the surface of each lymphocyte. During the course of an immune response to infections or immunizations, B cell clones specific of epitopes from the immunogen are expanded and activated, leading to production of specific antibodies. Among teleost fish, salmonids comprise key species for aquaculture. Rainbow trout ( Oncorhynchus mykiss ) and Atlantic salmon ( Salmo salar ) are especially important from a commercial point of view and have emerged as critical models for fish immunology. The growing interest to capture accurate and comprehensive antibody responses against common pathogens and vaccines has resulted in recent efforts to sequence the IG repertoire in these species. In this context, a unified and standardized nomenclature of salmonid IG heavy chain (IGH) genes is urgently required, to improve accuracy of annotation of adaptive immune receptor repertoire dataset generated by high-throughput sequencing (AIRRseq) and facilitate comparisons between studies and species. Interestingly, the assembly of salmonids IGH genomic sequences is challenging due to the presence of two large size duplicated IGH loci and high numbers of IG genes and pseudogenes. We used data available for Atlantic salmon to establish an IMGT standardized nomenclature of IGH genes in this species and then applied the IMGT rules to the rainbow trout IGH loci to set up a nomenclature, which takes into account the specificities of Salmonid loci. This unique, consistent nomenclature for Salmonid IGH genes was then used to construct IMGT sequence reference directories allowing accurate annotation of AIRRseq data. The complex issues raised by the genetic diversity of salmon and trout strains are discussed in the context of IG repertoire annotation., (Copyright © 2019 Magadan, Krasnov, Hadi-Saljoqi, Afanasyev, Mondot, Lallias, Castro, Salinas, Sunyer, Hansen, Koop, Lefranc and Boudinot.)
- Published
- 2019
- Full Text
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