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1. Case study on the identification and classification of small-scale flow patterns in flaring active region

Author

Philishvi, E., Shergelashvili, B. M., Buitendag, S., Raes, J., Poedts, S., and Khodachenko, M. L.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Physics - Computational Physics, Physics - Data Analysis, Statistics and Probability, Physics - Space Physics
Abstract

We propose a novel methodology to identity flows in the solar atmosphere and classify their velocities as either supersonic, subsonic, or sonic. The proposed methodology consists of three parts. First, an algorithm is applied to the Solar Dynamics Observatory (SDO) image data to locate and track flows, resulting in the trajectory of each flow over time. Thereafter, the differential emission measure inversion method is applied to six AIA channels along the trajectory of each flow in order to estimate its background temperature and sound speed. Finally, we classify each flow as supersonic, subsonic, or sonic by performing simultaneous hypothesis tests on whether the velocity bounds of the flow are larger, smaller, or equal to the background sound speed. The proposed methodology was applied to the SDO image data from the 171 {\AA} spectral line for the date 6 March 2012 from 12:22:00 to 12:35:00 and again for the date 9 March 2012 from 03:00:00 to 03:24:00. Eighteen plasma flows were detected, 11 of which were classified as supersonic, 3 as subsonic, and 3 as sonic at a $70\%$ level of significance. Out of all these cases, 2 flows cannot be strictly ascribed to one of the respective categories as they change from the subsonic state to supersonic and vice versa. We labelled them as a subclass of transonic flows. The proposed methodology provides an automatic and scalable solution to identify small-scale flows and to classify their velocities as either supersonic, subsonic, or sonic. We identified and classified small-scale flow patterns in flaring loops. The results show that the flows can be classified into four classes: sub-, super-, trans-sonic, and sonic. The detected flows from AIA images can be analyzed in combination with the other high-resolution observational data, such as Hi-C 2.1 data, and be used for the development of theories of the formation of flow patterns., Comment: 13 pages, 7 figures, Accepted for publication in A&A

Published
2020
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2. The polytropic index of solar coronal plasma in sunspot fan loops and its temperature dependence

Author

Prasad, S. Krishna, Raes, J. O., Van Doorsselaere, T., Magyar, N., and Jess, D. B.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

Observations of slow magneto-acoustic waves have been demonstrated to possess a number of applications in coronal seismology. Determination of the polytropic index ($\gamma$) is one such important application. Analysing the amplitudes of oscillations in temperature and density corresponding to a slow magneto-acoustic wave, the polytropic index in the solar corona has been calculated and based on the obtained value it has been inferred that thermal conduction is highly suppressed in a very hot loop in contrast to an earlier report of high thermal conduction in a relatively colder loop. In this study, using SDO/AIA data, we analysed slow magneto-acoustic waves propagating along sunspot fan loops from 30 different active regions and computed polytropic indices for several loops at multiple spatial positions. The obtained $\gamma$ values vary from 1.04$\pm$0.01 to 1.58$\pm$0.12 and most importantly display a temperature dependence indicating higher $\gamma$ at hotter temperatures. This behaviour brings both the previous studies to agreement and perhaps implies a gradual suppression of thermal conduction with increase in temperature of the loop. The observed phase shifts between temperature and density oscillations, however, are substantially larger than that expected from a classical thermal conduction and appear to be influenced by a line-of-sight integration effect on the emission measure., Comment: Accepted for publication in ApJ

Published
2018
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3. Observations of apparent superslow wave propagation in solar prominences

Author

Raes, J. O., Van Doorsselaere, T., Baes, M., and Wright, A. N.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

Phase mixing of standing continuum Alfv\'en waves and/or continuum slow waves in atmospheric magnetic structures such as coronal arcades can create the apparent effect of a wave propagating across the magnetic field. We observe a prominence with SDO/AIA on 2015 March 15 and find the presence of oscillatory motion. We aim to demonstrate that interpreting this motion as a magneto hydrodynamic (MHD) wave is faulty. We also connect the decrease of the apparent velocity over time with the phase mixing process, which depends on the curvature of the magnetic field lines. By measuring the displacement of the prominence at different heights to calculate the apparent velocity, we show that the propagation slows down over time, in accordance with the theoretical work of Kaneko et al. We also show that this propagation speed drops below what is to be expected for even slow MHD waves for those circumstances. We use a modified Kippenhahn-Schl\"uter prominence model to calculate the curvature of the magnetic field and fit our observations accordingly. Measuring three of the apparent waves, we get apparent velocities of 14, 8, and 4 km/s. Fitting a simple model for the magnetic field configuration, we obtain that the filament is located 103 Mm below the magnetic centre. We also obtain that the scale of the magnetic field strength in the vertical direction plays no role in the concept of apparent superslow waves and that the moment of excitation of the waves happened roughly one oscillation period before the end of the eruption that excited the oscillation. Some of the observed phase velocities are lower than expected for slow modes for the circumstances, showing that they rather fit with the concept of apparent superslow propagation. A fit with our magnetic field model allows for inferring the magnetic geometry of the prominence., Comment: 10 pages, 6 figures, 1 of which consists of 3 panels

Published
2017
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5. Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity

Author

Vanderbeke, L., Van Mol, P., Van Herck, Y., De Smet, F., Humblet-Baron, S., Martinod, K., Antoranz, A., Arijs, I., Boeckx, B., Bosisio, F. M., Casaer, M., Dauwe, D., De Wever, W., Dooms, C., Dreesen, E., Emmaneel, A., Filtjens, J., Gouwy, M., Gunst, J., Hermans, G., Jansen, S., Lagrou, K., Liston, A., Lorent, N., Meersseman, P., Mercier, T., Neyts, J., Odent, J., Panovska, D., Penttila, P. A., Pollet, E., Proost, P., Qian, J., Quintelier, K., Raes, J., Rex, S., Saeys, Y., Sprooten, J., Tejpar, S., Testelmans, D., Thevissen, K., Van Buyten, T., Vandenhaute, J., Van Gassen, S., Velásquez Pereira, L. C., Vos, R., Weynand, B., Wilmer, A., Yserbyt, J., Garg, A. D., Matthys, P., Wouters, C., Lambrechts, D., Wauters, E., and Wauters, J.

Published
2021
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6. DOP48 Faecal microbiota transplantation in active Ulcerative Colitis: Key lessons from a randomized controlled trial halted for futility

Author

Deleu, S, primary, Caenepeel, C, additional, Vazquez Castellanos, J F, additional, Arnauts, K, additional, Braekeleire, S, additional, Machiels, K, additional, Baert, F, additional, Mana, F, additional, Pouillon, L, additional, Hindryckx, P, additional, Lobaton Ortega, T, additional, Louis, E, additional, Franchimont, D, additional, Verstockt, B, additional, Ferrante, M, additional, Sabino, J, additional, Vieira-Silva, S, additional, Falony, G, additional, Raes, J, additional, and Vermeire, S, additional

Published
2024
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7. DOP86 FOod Additives on the Mucosal barrier study (FOAM): Effect of five emulsifiers on inflammation, intestinal permeability, and the microbiome: preliminary results

Author

Wellens, J, primary, Vanderstappen, J, additional, Hoekx, S, additional, Vissers, E, additional, Luppens, M, additional, Raes, J, additional, Verstockt, B, additional, Ferrante, M, additional, Verbeke, K, additional, Matthys, C, additional, Vermeire, S, additional, and Sabino, J, additional

Published
2024
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8. DOP43 Histologic improvement, attenuation of inflammation and microbiome modulation by engineered high acetate producing Saccharomyces boulardii in DSS-induced colitis

Author

Deleu, S, primary, Trindade de Carvalho, B, additional, Jacobs, I, additional, Vazquez Castellanos, J, additional, Verstockt, S, additional, Verstockt, B, additional, Arnauts, K, additional, Deprez, L, additional, Vissers, E, additional, Lenfant, M, additional, De Hertogh, G, additional, Huys, G, additional, Thevelein, J, additional, Raes, J, additional, and Vermeire, S, additional

Published
2024
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9. Multiomics Analyses to Deliver the Most Effective Treatment to Every Patient With Inflammatory Bowel Disease

Author

Weersma, R.K., Barrett, J.C., Vermeire, S., Xavier, R.J., Anderson, C.A., Wijmenga, C., Daly, M.J., Alm, E.J., Raes, J., Huttenhower, C., Stappenbeck, T., Netea, M., Kaser, A., Franke, A., McGovern, D.P., Colombel, J.F., van den Brink, G.R., Uhlig, H.H., Georges, M., Lees, C.W., Parkes, M., Giallourakis, C., Hart, A., Rioux, J.D., Sokol, H., Hurtado-Lorenzo, A., Yeretssian, G., Markus- de Kwaadsteniet, M.L., Festen, E.A., Rahmouni, S., Vieira-Silva, S., McIntyre, R.E., Moutsianas, L., Weersma, Rinse K., Xavier, Ramnik J., Vermeire, Severine, and Barrett, Jeffrey C.

Published
2018
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11. Oral dydrogesterone versus micronized vaginal progesterone for luteal phase support: a double-blind crossover study investigating pharmacokinetics and impact on the endometrium.

Author

Loreti, S, Thiele, K, Brucker, M De, Olsen, C, Centelles-Lodeiro, J, Bourgain, C, Waelput, W, Tournaye, H, Griesinger, G, Raes, J, Vieira-Silva, S, Arck, P, Blockeel, C, and Mackens, S

Subjects
LUTEAL phase, OVUM donation, INDUCED ovulation, INTRACYTOPLASMIC sperm injection, GENITALIA, CLOMIPHENE
Abstract

STUDY QUESTION How do plasma progesterone (P) and dydrogesterone (D) concentrations together with endometrial histology, transcriptomic signatures, and immune cell composition differ when oral dydrogesterone (O-DYD) or micronized vaginal progesterone (MVP) is used for luteal phase support (LPS)? SUMMARY ANSWER Although after O-DYD intake, even at steady-state, plasma D and 20αdihydrodydrogesterone (DHD) concentrations spiked in comparison to P concentrations, a similar endometrial signature was observed by histological and transcriptomic analysis of the endometrium. WHAT IS KNOWN ALREADY O-DYD for LPS has been proven to be noninferior compared to MVP in two phase III randomized controlled trials. Additionally, a combined individual participant data and aggregate data meta-analysis indicated that a higher pregnancy rate and live birth rate may be obtained in women receiving O-DYD versus MVP for LPS in fresh IVF/ICSI cycles. Little data are available on the pharmacokinetic (PK) profiles of O-DYD versus MVP and their potential molecular differences at the level of the reproductive organs, particularly at the endometrial level. STUDY DESIGN, SIZE, DURATION Thirty oocyte donors were planned to undergo two ovarian stimulation (OS) cycles with dual triggering (1.000 IU hCG + 0.2 mg triptorelin), each followed by 1 week of LPS: O-DYD or MVP, in a randomized, cross-over, double-blind, double-dummy fashion. On both the first and eighth days of LPS, serial blood samples upon first dosing were harvested for plasma D, DHD, and P concentration analyses. On Day 8 of LPS, an endometrial biopsy was collected for histologic examination, transcriptomics, and immune cell analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS All oocyte donors were <35 years old, had regular menstrual cycles, no intrauterine contraceptive device, anti-Müllerian hormone within normal range and a BMI ≤29 kg/m2. OS was performed on a GnRH antagonist protocol followed by dual triggering (1.000 IU hCG + 0.2 mg triptorelin) as soon as ≥3 follicles of 20 mm were present. Following oocyte retrieval, subjects initiated LPS consisting of MVP 200 mg or O-DYD 10 mg, both three times daily. D, DHD, and P plasma levels were measured using liquid chromatography–tandem mass spectrometry. Histological assessment was carried out using the Noyes criteria. Endometrial RNA-sequencing was performed for individual biopsies and differential gene expression was analyzed. Endometrial single-cell suspensions were created followed by flow cytometry for immune cell typing. MAIN RESULTS AND THE ROLE OF CHANCE A total of 21 women completed the entire study protocol. Subjects and stimulation characteristics were found to be similar between groups. Following the first dose of O-DYD, the average observed maximal plasma concentrations (C max) for D and DHD were 2.9 and 77 ng/ml, respectively. The C max for D and DHD was reached after 1.5 and 1.6 h (= T max), respectively. On the eighth day of LPS, the first administration of that day gave rise to a C max of 3.6 and 88 ng/ml for D and DHD, respectively. For both, the observed T max was 1.5 h. Following the first dose of MVP, the C max for P was 16 ng/ml with a T max of 4.2 h. On the eighth day of LPS, the first administration of that day showed a C max for P of 21 ng/ml with a T max of 7.3 h. All 42 biopsies showed endometrium in the secretory phase. The mean cycle day was 23.9 (±1.2) in the O-DYD group versus 24.0 (±1.3) in the MVP group. RNA-sequencing did not reveal significantly differentially expressed genes between samples of both study groups. The average Euclidean distance between samples following O-DYD was significantly lower than following MVP (respectively 12.1 versus 18.8, Mann–Whitney P  = 6.98e−14). Immune cell profiling showed a decrease of CD3 T-cell, γδ T-cell, and B-cell frequencies after MVP treatment compared to O-DYD, while the frequency of natural killer (NK) cells was significantly increased. LIMITATIONS, REASONS FOR CAUTION The main reason for caution is the small sample size, given the basic research nature of the project. The plasma concentrations are best estimates as this was not a formal PK study. Whole tissue bulk RNA-sequencing has been performed not correcting for bias caused by different tissue compositions across biopsies. WIDER IMPLICATIONS OF THE FINDINGS This is the first study comparing O-DYD/MVP, head-to-head, in a randomized design on a molecular level in IVF/ICSI. Plasma serum concentrations suggest that administration frequency is important, in addition to dose, specifically for O-DYD showing a rapid clearance. The molecular endometrial data are overall comparable and thus support the previously reported noninferior reproductive outcomes for O-DYD as compared to MVP. Further research is needed to explore the smaller intersample distance following O-DYD and the subtle changes detected in endometrial immune cells. STUDY FUNDING/COMPETING INTEREST(S) Not related to this work, C.Bl. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Organon, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. H.T. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Cooper Surgical, Gedeon-Richter, Cook, and Goodlife. S.M. has received honoraria for lectures, presentations, educational events, or scientific advice from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck and Oxolife. G.G. has received honoraria for lectures, presentations, educational events, or scientific advice from Merck, MSD, Organon, Ferring, Theramex, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, Guerbet, Cooper, Igyxos, and OxoLife. S.V.-S. is listed as inventor on two patents (WO2019115755A1 and WO2022073973A1), which are not related to this work. TRIAL REGISTRATION NUMBER EUDRACT 2018-000105-23 [ABSTRACT FROM AUTHOR]

Published
2024
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14. Effect Of Food Intake On Gastrointestinal Transit, Pressure And Ph In Normal-Weight And Obesity

Author

Steenackers, N., primary, Wauters, L., additional, Van der Schueren, B., additional, Augustijns, P., additional, Falony, G., additional, Koziolek, M., additional, Lannoo, M., additional, Mertens, A., additional, Meulemans, A., additional, Raes, J., additional, Vangoitsenhoven, R., additional, Vieira-Silva, S., additional, Weitschies, W., additional, Vanuytsel, T., additional, and Matthys, C., additional

Published
2023
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15. Determinants of community structure in the global plankton interactome

Author

Tara Oceans Coordinators, Lima-Mendez, G., Faust, K., Henry, N., Decelle, J., Colin, S., Carcillo, F., Chaffron, S., Ignacio-Espinosa, J. C., Roux, S., Vincent, F., Bittner, L., Darzi, Y., Wang, J., Audic, S., Berline, L., Bontempi, G., Cabello, A. M., Coppola, L., Cornejo-Castillo, F. M., d'Ovidio, F., De Meester, L., Ferrera, I., Garet-Delmas, M.-J., Guidi, L., Lara, E., Pesant, S., Royo-Llonch, M., Salazar, G., Sànchez, P., Sebastian, M., Souffreau, C., Dimier, C., Picheral, M., Searson, S., Kandels-Lewis, S., Gorsky, G., Not, F., Ogata, H., Speich, S., Stemmann, L., Weissenbach, J., Wincker, P., Acinas, S. G., Sunagawa, S., Bork, P., Sullivan, M. B., Karsenti, E., Bowler, C., de Vargas, C., and Raes, J.

Published
2015

16. Eukaryotic plankton diversity in the sunlit ocean

Author

Tara Oceans Coordinators, de Vargas, C., Audic, S., Henry, N., Decelle, J., Mahé, F., Logares, R., Lara, E., Berney, C., Le Bescot, N., Probert, I., Carmichael, M., Poulain, J., Romac, S., Colin, S., Aury, J.-M., Bittner, L., Chaffron, S., Dunthorn, M., Engelen, S., Flegontova, O., Guidi, L., Horák, A., Jaillon, O., Lima-Mendez, G., Lukeš, J., Malviya, S., Morard, R., Mulot, M., Scalco, E., Siano, R., Vincent, F., Zingone, A., Dimier, C., Picheral, M., Searson, S., Kandels-Lewis, S., Acinas, S. G., Bork, P., Bowler, C., Gorsky, G., Grimsley, N., Hingamp, P., Iudicone, D., Not, F., Ogata, H., Pesant, S., Raes, J., Sieracki, M. E., Speich, S., Stemmann, L., Sunagawa, S., Weissenbach, J., Wincker, P., and Karsenti, E.

Published
2015

17. Structure and function of the global ocean microbiome

Author

Tara Oceans Coordinators, Sunagawa, S., Coelho, L. P., Chaffron, S., Kultima, J. R., Labadie, K., Salazar, G., Djahanschiri, B., Zeller, G., Mende, D. R., Alberti, A., Cornejo-Castillo, F. M., Costea, P. I., Cruaud, C., d'Ovidio, F., Engelen, S., Ferrera, I., Gasol, J. M., Guidi, L., Hildebrand, F., Kokoszka, F., Lepoivre, C., Lima-Mendez, G., Poulain, J., Poulos, B. T., Royo-Llonch, M., Sarmento, H., Vieira-Silva, S., Dimier, C., Picheral, M., Searson, S., Kandels-Lewis, S., Bowler, C., de Vargas, C., Gorsky, G., Grimsley, N., Hingamp, P., Iudicone, D., Jaillon, O., Not, F., Ogata, H., Pesant, S., Speich, S., Stemmann, L., Sullivan, M. B., Weissenbach, J., Wincker, P., Karsenti, E., Raes, J., Acinas, S. G., and Bork, P.

Published
2015

18. P921 FMT in UC is associated with a decrease in Bacteroides-2 enterotype and response with baseline RNA and microbiota signatures

Author

Deleu, S, primary, Caenepeel, C, additional, Verstockt, S, additional, Vazquez Castellanos, J F, additional, Arnauts, K, additional, Braekeleire, S, additional, Machiels, K, additional, Baert, F, additional, Mana, F, additional, Pouillon, L, additional, Hindryckx, P, additional, Lobaton Ortega, T, additional, Louis, E, additional, Franchimont, D, additional, Verstockt, B, additional, Ferrante, M, additional, Sabino, J, additional, Vieira-Silva, S, additional, Falony, G, additional, Raes, J, additional, and Vermeire, S, additional

Published
2023
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28. SO-26 Identification and quantification of the microbiome in colorectal cancer metastases

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service d'oncologie médicale, Stevens, P, Llorens-Rico, V., Baldin, Paméla, Gofflot, S., Craciun, L., Fabienne, G., Sadones, J., Buys, M., Raes, J., Van den Eynde, Marc, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service d'oncologie médicale, Stevens, P, Llorens-Rico, V., Baldin, Paméla, Gofflot, S., Craciun, L., Fabienne, G., Sadones, J., Buys, M., Raes, J., and Van den Eynde, Marc

Abstract

Background: Recent research has identified the existence of living bacteria in the tumor microenvironment, as well as cancer-specific bacteria in blood of patients. Early evidence suggested a role of the gut and tissue microbiome in the development of colorectal cancer (CRC). However, the part of this intra-tumor microbiome in promoting or aiding metastasis to distant organs remains unexplored. Interestingly, similar bacterial strains from CRC primary tumors have been identified in patientmatched liver metastases. Few mechanistic hypotheses have been proposed of how bacterial translocation to distant sites occurs, or whether the tumor-resident microbiome can influence the spreading or the behavior of metastases and their local immune response. Methods: We aimed to characterize the intra-tumor bacterial signature of metastatic colorectal cancer (mCRC) through a large-scale study with different cohorts from several biobanks in Belgium. We collected 378 frozen samples from 99 patients composed by 104 primary colorectal tumors (PT) and 99 patient-matched liver metastases (LMT), both associated with normal adjacent tissue (NAT) as control (n ¼ 83 and 58, respectively). We added primary liver tumors (hepatocellular carcinoma (HCC, n¼28) and cholangiocarcinoma (CGC, n¼6)) from 27 patients as comparative cohort for LMT. The V4 region of the bacterial 16S rRNA gene was sequenced. The computational DADA2 pipeline was used to process the sequencing data and determine the abundance of amplicon sequence variants (ASV). We strictly applied sterile conditions from sample collection to sequencing, with negative and positive controls along the process to minimize contamination and misinterpretation of the results. Potential contaminants were removed bioinformatically by applying a series of stringent filters. Results: Bacterial sequences were identified in all tissue types. Based on preliminary results, the principal component analysis based on bacterial composition of the samples r

Published
2022

31. Combinatorial, additive and dose-dependent drug-microbiome associations

Author

Forslund, SK, Chakaroun, R, Zimmermann-Kogadeeva, M, Markó, L, Aron-Wisnewsky, J, Nielsen, T, Moitinho-Silva, L, Schmidt, TSB, Falony, G, Vieira-Silva, S, Adriouch, S, Alves, RJ, Assmann, K, Bastard, J-P, Birkner, T, Caesar, R, Chilloux, J, Coelho, LP, Fezeu, L, Galleron, N, Helft, G, Isnard, R, Ji, B, Kuhn, M, Le Chatelier, E, Myridakis, A, Olsson, L, Pons, N, Prifti, E, Quinquis, B, Roume, H, Salem, J-E, Sokolovska, N, Tremaroli, V, Valles-Colomer, M, Lewinter, C, Søndertoft, NB, Pedersen, HK, Hansen, TH, Amouyal, C, Andersson Galijatovic, EA, Andreelli, F, Barthelemy, O, Batisse, J-P, Belda, E, Berland, M, Bittar, R, Blottière, H, Bosquet, F, Boubrit, R, Bourron, O, Camus, M, Cassuto, D, Ciangura, C, Collet, J-P, Dao, M-C, Djebbar, M, Doré, A, Engelbrechtsen, L, Fellahi, S, Fromentin, S, Galan, P, Gauguier, D, Giral, P, Hartemann, A, Hartmann, B, Holst, JJ, Hornbak, M, Hoyles, L, Hulot, J-S, Jaqueminet, S, Jørgensen, NR, Julienne, H, Justesen, J, Kammer, J, Krarup, N, Kerneis, M, Khemis, J, Kozlowski, R, Lejard, V, Levenez, F, Lucas-Martini, L, Massey, R, Martinez-Gili, L, Maziers, N, Medina-Stamminger, J, Montalescot, G, Moute, S, Neves, AL, Olanipekun, M, Le Pavin, LP, Poitou, C, Pousset, F, Pouzoulet, L, Rodriguez-Martinez, A, Rouault, C, Silvain, J, Svendstrup, M, Swartz, T, Vanduyvenboden, T, Vatier, C, Walther, S, Gøtze, JP, Køber, L, Vestergaard, H, Hansen, T, Zucker, J-D, Hercberg, S, Oppert, J-M, Letunic, I, Nielsen, J, Bäckhed, F, Ehrlich, SD, Dumas, M-E, Raes, J, Pedersen, O, Clément, K, Stumvoll, M, Bork, P, The MetaCardis Consortium (Hoyles, L.), European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Universität Leipzig, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Copenhagen = Københavns Universitet (UCPH), University of New South Wales [Sydney] (UNSW), Paul Scherrer Institute (PSI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Heidelberg University, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], University of Gothenburg (GU), Imperial College London, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chalmers University of Technology [Gothenburg, Sweden], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Biobyte Solutions [Heidelberg, Germany] (BS), IT University of Copenhagen (ITU), Sahlgrenska University Hospital [Gothenburg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, McGill University and Genome Quebec Innovation Centre, Helmholtz Institute Ulm (HIU), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Würzburg = Universität Würzburg, Yonsei University, MetaCardis Consortium*: Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy, Jean-Paul Batisse, Eugeni Belda, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Cecile Ciangura, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Sebastien Fromentin, Pilar Galan, Dominique Gauguier, Philippe Giral, Agnes Hartemann, Bolette Hartmann, Jens Juul Holst, Malene Hornbak, Lesley Hoyles, Jean-Sebastien Hulot, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Ruby Kozlowski, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Laura Martinez-Gili, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moute, Ana Luisa Neves, Michael Olanipekun, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Andrea Rodriguez-Martinez, Christine Rouault, Johanne Silvain, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), Dumas, Marc-Emmanuel, Universität Leipzig [Leipzig], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Henri Mondor, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-1901(ex CIC-1421)), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK

Subjects
Clostridiales, Science & Technology, Multidisciplinary, ANTIBIOTIC USE, IMPACT, Microbiota, [SDV]Life Sciences [q-bio], HUMAN GUT MICROBIOME, Atherosclerosis, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, PROTON PUMP INHIBITORS, Cardiovascular and Metabolic Diseases, GUIDELINE, Metabolome, MANAGEMENT, Humans, Science & Technology - Other Topics, ALTERS
Abstract

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. ispartof: NATURE vol:600 issue:7889 pages:500-+ ispartof: location:England status: published

Published
2021
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35. OP03 Standardized faecal microbiota transplantation with microbiome-guided donor selection in active UC patients: A randomized, placebo-controlled intervention study

Author

Caenepeel, C, primary, Deleu, S, additional, Arnauts, K, additional, Vazquez Castellanos, J F, additional, Braekeleire, S, additional, Machiels, K, additional, Baert, F, additional, Mana, F, additional, Pouillon, L, additional, Hindryckx, P, additional, Lobaton, T, additional, Louis, E, additional, Franchimont, D, additional, Ferrante, M, additional, Sabino, J, additional, Vieira-Silva, S, additional, Falony, G, additional, Raes, J, additional, and Vermeire, S, additional

Published
2022
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38. Eukaryotic plankton diversity in the sunlit ocean

Author

de Vargas, C., Audic, S., Henry, N., Decelle, J., Mahé, F., Logares, R., Lara, E., Berney, C., Le Bescot, N., Probert, I., Carmichael, M., Poulain, J., Romac, S., Colin, S., Aury, J.-M., Bittner, L., Chaffron, S., Dunthorn, M., Engelen, S., Flegontova, O., Guidi, L., Horák, A., Jaillon, O., Lima-Mendez, G., Lukeš, J., Malviya, S., Morard, R., Mulot, M., Scalco, E., Siano, R., Vincent, F., Zingone, A., Dimier, C., Picheral, M., Searson, S., Kandels-Lewis, S., Oceans Coordinators, Tara, Acinas, S. G., Bork, P., Bowler, C., Gorsky, G., Grimsley, N., Hingamp, P., Iudicone, D., Not, F., Ogata, H., Pesant, S., Raes, J., Sieracki, M. E., Speich, S., Stemmann, L., Sunagawa, S., Weissenbach, J., Wincker, P., and Karsenti, E.

Published
2015

39. Determinants of community structure in the global plankton interactome

Author

Lima-Mendez, G., Faust, K., Henry, N., Decelle, J., Colin, S., Carcillo, F., Chaffron, S., Ignacio-Espinosa, J. C., Roux, S., Vincent, F., Bittner, L., Darzi, Y., Wang, J., Audic, S., Berline, L., Bontempi, G., Cabello, A. M., Coppola, L., Cornejo-Castillo, F. M., dʼOvidio, F., De Meester, L., Ferrera, I., Garet-Delmas, M.-J., Guidi, L., Lara, E., Pesant, S., Royo-Llonch, M., Salazar, G., Sánchez, P., Sebastian, M., Souffreau, C., Dimier, C., Picheral, M., Searson, S., Kandels-Lewis, S., Oceans Coordinators, Tara, Gorsky, G., Not, F., Ogata, H., Speich, S., Stemmann, L., Weissenbach, J., Wincker, P., Acinas, S. G., Sunagawa, S., Bork, P., Sullivan, M. B., Karsenti, E., Bowler, C., de Vargas, C., and Raes, J.

Published
2015

40. Structure and function of the global ocean microbiome

Author

Sunagawa, S., Coelho, L. P., Chaffron, S., Kultima, J. R., Labadie, K., Salazar, G., Djahanschiri, B., Zeller, G., Mende, D. R., Alberti, A., Cornejo-Castillo, F. M., Costea, P. I., Cruaud, C., dʼOvidio, F., Engelen, S., Ferrera, I., Gasol, J. M., Guidi, L., Hildebrand, F., Kokoszka, F., Lepoivre, C., Lima-Mendez, G., Poulain, J., Poulos, B. T., Royo-Llonch, M., Sarmento, H., Vieira-Silva, S., Dimier, C., Picheral, M., Searson, S., Kandels-Lewis, S., Oceans Coordinators, Tara, Bowler, C., de Vargas, C., Gorsky, G., Grimsley, N., Hingamp, P., Iudicone, D., Jaillon, O., Not, F., Ogata, H., Pesant, S., Speich, S., Stemmann, L., Sullivan, M. B., Weissenbach, J., Wincker, P., Karsenti, E., Raes, J., Acinas, S. G., and Bork, P.

Published
2015

41. Sharp bound on the threshold metric dimension of trees

Author

Bartha, Zsolt, Komj��thy, J��lia, and Raes, J��rvi

Subjects
FOS: Mathematics, Combinatorics (math.CO), 05C69 (Primary) 05C35, 05C05, 05C38 (Secondary)
Abstract

The threshold-$k$ metric dimension ($\mathrm{Tmd}_k$) of a graph is the minimum number of sensors -- a subset of the vertex set -- needed to uniquely identify any vertex in the graph, solely based on its distances from the sensors, when the measuring radius of a sensor is $k$. We give a sharp lower bound on the $\mathrm{Tmd}_k$ of trees, depending only on the number of vertices $n$ and the measuring radius $k$. This sharp lower bound grows linearly in $n$ with leading coefficient $3/(k^2+4k+3+\mathbf{1}\{k\equiv 1\pmod 3\})$, disproving earlier conjectures by Tillquist et al. in arXiv:2106.14314 that suspected $n/(\lfloor k^2/4\rfloor +2k)$ as main order term. We provide a construction for the largest possible trees with a given $\mathrm{Tmd}_k$ value. The proof that our optimal construction cannot be improved relies on edge-rewiring procedures of arbitrary (suboptimal) trees with arbitrary resolving sets, which reveal the structure of how small subsets of sensors measure and resolve certain areas in the tree that we call the attraction of those sensors. The notion of `attraction of sensors' might be useful in other contexts beyond trees to solve related problems. We also provide an improved lower bound on the $\mathrm{Tmd}_k$ of arbitrary trees that takes into account the structural properties of the tree, in particular, the number and length of simple paths of degree-two vertices terminating in leaf vertices. This bound complements arXiv:2106.14314, where only trees without degree-two vertices were considered, except the simple case of a single path., 35 pages, 4 figures

Published
2021
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44. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology (vol 11, 5881, 2020)

Author

Molinaro, A, Lassen, PB, Henricsson, M, Wu, H, Adriouch, S, Belda, E, Chakaroun, R, Nielsen, T, Bergh, P-O, Rouault, C, Andre, S, Marquet, F, Andreelli, F, Salem, J-E, Assmann, K, Bastard, J-P, Forslund, S, Le Chatelier, E, Falony, G, Pons, N, Prifti, E, Quinquis, B, Roume, H, Vieira-Silva, S, Hansen, TH, Pedersen, HK, Lewinter, C, Sonderskov, NB, Kober, L, Vestergaard, H, Hansen, T, Zucker, J-D, Galan, P, Dumas, M-E, Raes, J, Oppert, J-M, Letunic, I, Nielsen, J, Bork, P, Ehrlich, SD, Stumvoll, M, Pedersen, O, Aron-Wisnewsky, J, Clement, K, Backhed, F, and Commission of the European Communities

Subjects
Multidisciplinary Sciences, MetaCardis Consortium, Science & Technology, Science & Technology - Other Topics
Published
2020

46. Reporting guidelines for human microbiome research: the STORMS checklist

Author

Mirzayi, C, Renson, A, Furlanello, C, Sansone, SA, Zohra, F, Elsafoury, S, Geistlinger, L, Kasselman, LJ, Eckenrode, K, van de Wijgert, J, Loughman, Amy, Marques, FZ, MacIntyre, DA, Arumugam, M, Azhar, R, Beghini, F, Bergstrom, K, Bhatt, A, Bisanz, JE, Braun, J, Bravo, HC, Buck, GA, Bushman, F, Casero, D, Clarke, G, Collado, MC, Cotter, PD, Cryan, JF, Demmer, RT, Devkota, S, Elinav, E, Escobar, JS, Fettweis, J, Finn, RD, Fodor, AA, Forslund, S, Franke, A, Gilbert, J, Grice, E, Haibe-Kains, B, Handley, S, Herd, P, Holmes, S, Jacobs, JP, Karstens, L, Knight, R, Knights, D, Koren, O, Kwon, DS, Langille, M, Lindsay, B, McGovern, D, McHardy, AC, McWeeney, S, Mueller, NT, Nezi, L, Olm, M, Palm, N, Pasolli, E, Raes, J, Redinbo, MR, Rühlemann, M, Balfour Sartor, R, Schloss, PD, Schriml, L, Segal, E, Shardell, M, Sharpton, T, Smirnova, E, Sokol, H, Sonnenburg, JL, Srinivasan, S, Thingholm, LB, Turnbaugh, PJ, Upadhyay, V, Walls, RL, Wilmes, P, Yamada, T, Zeller, G, Zhang, M, Zhao, N, Zhao, L, Bao, W, Culhane, A, Devanarayan, V, Dopazo, J, Fan, X, Fischer, M, Jones, W, Kusko, R, Mason, CE, Mercer, TR, Scherer, A, Shi, L, Thakkar, S, Tong, W, Wolfinger, R, Hunter, C, Mirzayi, C, Renson, A, Furlanello, C, Sansone, SA, Zohra, F, Elsafoury, S, Geistlinger, L, Kasselman, LJ, Eckenrode, K, van de Wijgert, J, Loughman, Amy, Marques, FZ, MacIntyre, DA, Arumugam, M, Azhar, R, Beghini, F, Bergstrom, K, Bhatt, A, Bisanz, JE, Braun, J, Bravo, HC, Buck, GA, Bushman, F, Casero, D, Clarke, G, Collado, MC, Cotter, PD, Cryan, JF, Demmer, RT, Devkota, S, Elinav, E, Escobar, JS, Fettweis, J, Finn, RD, Fodor, AA, Forslund, S, Franke, A, Gilbert, J, Grice, E, Haibe-Kains, B, Handley, S, Herd, P, Holmes, S, Jacobs, JP, Karstens, L, Knight, R, Knights, D, Koren, O, Kwon, DS, Langille, M, Lindsay, B, McGovern, D, McHardy, AC, McWeeney, S, Mueller, NT, Nezi, L, Olm, M, Palm, N, Pasolli, E, Raes, J, Redinbo, MR, Rühlemann, M, Balfour Sartor, R, Schloss, PD, Schriml, L, Segal, E, Shardell, M, Sharpton, T, Smirnova, E, Sokol, H, Sonnenburg, JL, Srinivasan, S, Thingholm, LB, Turnbaugh, PJ, Upadhyay, V, Walls, RL, Wilmes, P, Yamada, T, Zeller, G, Zhang, M, Zhao, N, Zhao, L, Bao, W, Culhane, A, Devanarayan, V, Dopazo, J, Fan, X, Fischer, M, Jones, W, Kusko, R, Mason, CE, Mercer, TR, Scherer, A, Shi, L, Thakkar, S, Tong, W, Wolfinger, R, and Hunter, C

Published
2021

48. Deletions involving long-range conserved nongenic sequences upstream and downstream of FOXL2 as a novel disease-causing mechanism in blepharophimosis syndrome

Author

Beysen, D., Raes, J., Leroy, B.P., Lucassen, A., Yates, J.R.W., Clayton-Smith, J., Ilyina, H., Brooks, S. Sklower, Christin-Maitre, S., Fellous, M., Fryns, J.P., Kim, J.R., Lapunzina, P., Lemyre, E., Meire, F., Messiaen, L.M., Oley, C., Splitt, M., Thomson, J., Van de Peer, Y., Veitia, R.A., De Paepe, A., and De Baere, E.

Subjects
Human genetics -- Research, Genetic disorders -- Research, Chromosome abnormalities -- Research, Biological sciences
Published
2005

50. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis [plus Methods, Extended data figures, Supplementary information, and Nature Research reporting summary]

Author

Vieira-Silva, S., Falony, G., Belda, E., Nielsen, T., Aron-Wisnewsky, J., Chakaroun, R., Forslund, S.F., Assmann, K., Valles-Colomer, M., Nguyen, T.T.D., Proost, S., Prifti, E., Tremaroli, V., Pons, N., Le Chatelier, E., Andreelli, F., Bastard, J.P., Coelho, L.P., Galleron, N., Hulot, J.S., Lewinter, C., Pedersen, H.K., Quinquis, B., Rouault, C., Roume, H., Salem, J.E., Søndertoft, N.B., Touch, S., Dumas, M.E., Ehrlich, S.D., Galan, P., Gøtze, J.P., Hansen, T.H., Holst, J.S., Køber, L., Letunic, I., Nielsen, J., Oppert, J.M., Stumvoll, M., Vestergaard, H., Zucker, Jean-Daniel, Bork, P., Pedersen, O., Bäckhed, F., Clément, K., Raes, J., Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Sorbonne Université (SU)-Universtié Yaoundé 1 [Cameroun]-Université Cadi Ayyad [Marrakech] (UCA)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Institut de Recherche pour le Développement (IRD [France-Nord]), Service de diabétologie [CHU Pitié-Salpétrière], Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de pharmacologie biologique [CHU Pitié-Salpêtrière], CIC Paris Est, Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)

Subjects
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease. Reported changes in stool consistency and inflammation status during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

Published
2020
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