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1. Major depletion of insulin sensitivity-associated taxa in the gut microbiome of persons living with HIV controlled by antiretroviral drugs

Author

Belda, Eugeni, Capeau, Jacqueline, Zucker, Jean-Daniel, Chatelier, Emmanuelle Le, Pons, Nicolas, Oñate, Florian Plaza, Quinquis, Benoit, Alili, Rohia, Fellahi, Soraya, Katlama, Christine, Clément, Karine, Fève, Bruno, Jaureguiberry, Stéphane, Goujard, Cécile, Lambotte, Olivier, Doré, Joël, Prifti, Edi, and Bastard, Jean-Philippe

Published
2024
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2. Perturbation and resilience of the gut microbiome up to 3 months after β-lactams exposure in healthy volunteers suggest an important role of microbial β-lactamases

Author

d’Humières, Camille, Delavy, Margot, Alla, Laurie, Ichou, Farid, Gauliard, Emilie, Ghozlane, Amine, Levenez, Florence, Galleron, Nathalie, Quinquis, Benoit, Pons, Nicolas, Mullaert, Jimmy, Bridier-Nahmias, Antoine, Condamine, Bénédicte, Touchon, Marie, Rainteau, Dominique, Lamazière, Antonin, Lesnik, Philippe, Ponnaiah, Maharajah, Lhomme, Marie, Sertour, Natacha, Devente, Savannah, Docquier, Jean-Denis, Bougnoux, Marie-Elisabeth, Tenaillon, Olivier, Magnan, Mélanie, Ruppé, Etienne, Grall, Nathalie, Duval, Xavier, Ehrlich, Dusko, Mentré, France, Denamur, Erick, Rocha, Eduardo P. C., Le Chatelier, Emmanuelle, and Burdet, Charles

Published
2024
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4. The gut microbiota in multiple sclerosis varies with disease activity

Author

Thirion, Florence, Sellebjerg, Finn, Fan, Yong, Lyu, Liwei, Hansen, Tue H., Pons, Nicolas, Levenez, Florence, Quinquis, Benoit, Stankevic, Evelina, Søndergaard, Helle B., Dantoft, Thomas M., Poulsen, Casper S., Forslund, Sofia K., Vestergaard, Henrik, Hansen, Torben, Brix, Susanne, Oturai, Annette, Sørensen, Per Soelberg, Ehrlich, Stanislav D., and Pedersen, Oluf

Published
2023
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6. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author

Fromentin, Sebastien, Forslund, Sofia K., Chechi, Kanta, Aron-Wisnewsky, Judith, Chakaroun, Rima, Nielsen, Trine, Tremaroli, Valentina, Ji, Boyang, Prifti, Edi, Myridakis, Antonis, Chilloux, Julien, Andrikopoulos, Petros, Fan, Yong, Olanipekun, Michael T., Alves, Renato, Adiouch, Solia, Bar, Noam, Talmor-Barkan, Yeela, Belda, Eugeni, Caesar, Robert, Coelho, Luis Pedro, Falony, Gwen, Fellahi, Soraya, Galan, Pilar, Galleron, Nathalie, Helft, Gerard, Hoyles, Lesley, Isnard, Richard, Le Chatelier, Emmanuelle, Julienne, Hanna, Olsson, Lisa, Pedersen, Helle Krogh, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Schmidt, Thomas S. B., Vieira-Silva, Sara, Li, Peishun, Zimmermann-Kogadeeva, Maria, Lewinter, Christian, Søndertoft, Nadja B., Hansen, Tue H., Gauguier, Dominique, Gøtze, Jens Peter, Køber, Lars, Kornowski, Ran, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Hercberg, Serge, Letunic, Ivica, Bäckhed, Fredrik, Oppert, Jean-Michel, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Stumvoll, Michael, Segal, Eran, Clément, Karine, Dumas, Marc-Emmanuel, Ehrlich, S. Dusko, and Pedersen, Oluf

Published
2022
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8. Combinatorial, additive and dose-dependent drug–microbiome associations

Author

Forslund, Sofia K., Chakaroun, Rima, Zimmermann-Kogadeeva, Maria, Markó, Lajos, Aron-Wisnewsky, Judith, Nielsen, Trine, Moitinho-Silva, Lucas, Schmidt, Thomas S. B., Falony, Gwen, Vieira-Silva, Sara, Adriouch, Solia, Alves, Renato J., Assmann, Karen, Bastard, Jean-Philippe, Birkner, Till, Caesar, Robert, Chilloux, Julien, Coelho, Luis Pedro, Fezeu, Leopold, Galleron, Nathalie, Helft, Gerard, Isnard, Richard, Ji, Boyang, Kuhn, Michael, Le Chatelier, Emmanuelle, Myridakis, Antonis, Olsson, Lisa, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Tremaroli, Valentina, Valles-Colomer, Mireia, Lewinter, Christian, Søndertoft, Nadja B., Pedersen, Helle Krogh, Hansen, Tue H., Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Hercberg, Serge, Oppert, Jean-Michel, Letunic, Ivica, Nielsen, Jens, Bäckhed, Fredrik, Ehrlich, S. Dusko, Dumas, Marc-Emmanuel, Raes, Jeroen, Pedersen, Oluf, Clément, Karine, Stumvoll, Michael, and Bork, Peer

Published
2021
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9. Perturbation and resilience of the gut microbiome up to 3 months after β-lactams exposure in healthy volunteers suggest an important role of microbial β-lactamases.

Author

d'Humières, Camille, Delavy, Margot, Alla, Laurie, Ichou, Farid, Gauliard, Emilie, Ghozlane, Amine, Levenez, Florence, Galleron, Nathalie, Quinquis, Benoit, Pons, Nicolas, Mullaert, Jimmy, Bridier-Nahmias, Antoine, Condamine, Bénédicte, Touchon, Marie, Rainteau, Dominique, Lamazière, Antonin, Lesnik, Philippe, Ponnaiah, Maharajah, Lhomme, Marie, and Sertour, Natacha

Subjects
GUT microbiome, VOLUNTEERS, DRUG resistance in bacteria, MICROBIAL metabolites, HUMAN microbiota, VOLUNTEER service, CEFOTAXIME, LACTAMS
Abstract

Background: Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience. Results: While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools. Conclusions: In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous β-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon. 64G36U-BwhYzB4Dx7Xcq3U Video Abstract [ABSTRACT FROM AUTHOR]

Published
2024
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10. Evaluation of an Adapted Semi-Automated DNA Extraction for Human Salivary Shotgun Metagenomics

Author

Meslier, Victoria, primary, Menozzi, Elisa, additional, David, Aymeric, additional, Morabito, Christian, additional, Lucas Del Pozo, Sara, additional, Famechon, Alexandre, additional, North, Janet, additional, Quinquis, Benoit, additional, Koletsi, Sofia, additional, Macnaughtan, Jane, additional, Mezabrovschi, Roxana, additional, Ehrlich, S. Dusko, additional, Schapira, Anthony H. V., additional, and Almeida, Mathieu, additional

Published
2023
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11. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

Author

Routy, Bertrand, Le Chatelier, Emmanuelle, Derosa, Lisa, Duong, Connie P. M., Alou, Maryam Tidjani, Daillère, Romain, Fluckiger, Aurélie, Messaoudene, Meriem, Rauber, Conrad, Roberti, Maria P., Fidelle, Marine, Flament, Caroline, Poirier-Colame, Vichnou, Opolon, Paule, Klein, Christophe, Iribarren, Kristina, Mondragón, Laura, Jacquelot, Nicolas, Qu, Bo, Ferrere, Gladys, Clémenson, Céline, Mezquita, Laura, Masip, Jordi Remon, Naltet, Charles, Brosseau, Solenn, Kaderbhai, Coureche, Richard, Corentin, Rizvi, Hira, Levenez, Florence, Galleron, Nathalie, Quinquis, Benoit, Pons, Nicolas, Ryffel, Bernhard, Minard-Colin, Véronique, Gonin, Patrick, Soria, Jean-Charles, Deutsch, Eric, Loriot, Yohann, Ghiringhelli, François, Zalcman, Gérard, Goldwasser, François, Escudier, Bernard, Hellmann, Matthew D., Eggermont, Alexander, Raoult, Didier, Albiges, Laurence, Kroemer, Guido, and Zitvogel, Laurence

Published
2018

12. Driving gut microbiota enterotypes through host genetics

Author

Rogel-Gaillard, Claire, primary, Larzul, Catherine, additional, Estellé, Jordi, additional, Borey, Marion, additional, Blanc, Fany, additional, Lemonnier, Gaëtan, additional, Jardet, Deborah, additional, Lecardonnel, Jérôme, additional, Billon, Yvon, additional, Thiam, Mamadou-Gabou, additional, Oñate, Florian Plaza, additional, Quinquis, Benoit, additional, and Galleron, Nathalie, additional

Published
2023
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13. Driving gut microbiota enterotypes through host genetics

Author

Larzul, Catherine, primary, Estellé, Jordi, additional, Borey, Marion, additional, Blanc, Fany, additional, Lemonnier, Gaëtan, additional, Billon, Yvon, additional, Thiam, Mamadou-Gabou, additional, Quinquis, Benoit, additional, Galleron, Nathalie, additional, Jardet, Deborah, additional, Lecardonnel, Jérôme, additional, Oñate, Florian Plaza, additional, and Rogel-Gaillard, Claire, additional

Published
2023
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14. Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa

Author

Coutry, Nathalie, primary, Nguyen, Julie, additional, Soualhi, Salima, additional, Gerbe, François, additional, Meslier, Victoria, additional, Dardalhon, Valérie, additional, Almeida, Mathieu, additional, Quinquis, Benoit, additional, Thirion, Florence, additional, Herbert, Fabien, additional, Gasmi, Imène, additional, Lamrani, Ali, additional, Giordano, Alicia, additional, Cesses, Pierre, additional, Garnier, Laure, additional, Thirard, Steeve, additional, Greuet, Denis, additional, Cazevieille, Chantal, additional, Bernex, Florence, additional, Bressuire, Christelle, additional, Winton, Douglas, additional, Matsumoto, Ichiro, additional, Blottière, Hervé M., additional, Taylor, Naomi, additional, and Jay, Philippe, additional

Published
2023
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15. Evaluation of an adapted semi-automated DNA extraction for human salivary shotgun metagenomics

Author

Almeida, Mathieu, primary, Meslier, Victoria, additional, Menozzi, Elisa, additional, David, Aymeric, additional, Morabito, Christian, additional, Pozo, Sara Lucas Del, additional, Famechon, Alexandre, additional, North, Janet, additional, Quinquis, Benoit, additional, Koletsi, Sofia, additional, Macnaughtan, Jane, additional, Mezabrovschi, Roxana, additional, Ehrlich, S. Dusko, additional, and Schapira, Anthony HV., additional

Published
2023
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16. Comparative Genome Analysis of Enterococcus cecorum Reveals Intercontinental Spread of a Lineage of Clinical Poultry Isolates

Author

Laurentie, Jeanne, primary, Loux, Valentin, additional, Hennequet-Antier, Christelle, additional, Chambellon, Emilie, additional, Deschamps, Julien, additional, Trotereau, Angélina, additional, Furlan, Sylviane, additional, Darrigo, Claire, additional, Kempf, Florent, additional, Lao, Julie, additional, Milhes, Marine, additional, Roques, Céline, additional, Quinquis, Benoit, additional, Vandecasteele, Céline, additional, Boyer, Roxane, additional, Bouchez, Olivier, additional, Repoila, Francis, additional, Le Guennec, Jean, additional, Chiapello, Hélène, additional, Briandet, Romain, additional, Helloin, Emmanuelle, additional, Schouler, Catherine, additional, Kempf, Isabelle, additional, and Serror, Pascale, additional

Published
2023
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17. In Vitro Modelling of Oral Microbial Invasion in the Human Colon

Author

Etienne-Mesmin, Lucie, primary, Meslier, Victoria, additional, Uriot, Ophélie, additional, Fournier, Elora, additional, Deschamps, Charlotte, additional, Denis, Sylvain, additional, David, Aymeric, additional, Jegou, Sarah, additional, Morabito, Christian, additional, Quinquis, Benoit, additional, Thirion, Florence, additional, Plaza Oñate, Florian, additional, Le Chatelier, Emmanuelle, additional, Ehrlich, S. Dusko, additional, Blanquet-Diot, Stéphanie, additional, and Almeida, Mathieu, additional

Published
2023
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18. Perturbation and resilience of the gut microbiome up to three months after β-lactams exposure in healthy volunteers suggest an important role of endogenous β-lactamases

Author

d'Humières, Camille, primary, Delavy, Margot, additional, Alla, Laurie, additional, Ichou, Farid, additional, gauliard, Emilie, additional, Ghozlane, Amine, additional, Levenez, Florence, additional, Galleron, Nathalie, additional, Quinquis, Benoit, additional, Pons, Nicolas, additional, Mullaert, Jimmy, additional, Bridier-Nahmias, Antoine, additional, Condamine, Bénédicte, additional, Touchon, Marie, additional, Rainteau, Dominique, additional, Lamazière, Antonin, additional, Lesnik, Philippe, additional, Ponnaiah, Maharajah, additional, Lhomme, Marie, additional, Sertour, Natacha, additional, Devente, Savannah, additional, Docquier, Jean-Denis, additional, Bougnoux, Marie-Elisabeth, additional, Tenaillon, Olivier, additional, Magnan, Mélanie, additional, Ruppe, Etienne, additional, Grall, Nathalie, additional, Duval, Xavier, additional, Ehrlich, Dusko, additional, Mentre, France, additional, Denamur, erick, additional, Rocha, Eduardo P C, additional, Chatelier, Emmanuelle Le, additional, and Burdet, Charles, additional

Published
2023
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19. Comparative genome analysis ofEnterococcus cecorumreveals intercontinental spread of a lineage of clinical poultry isolates

Author

Laurentie, Jeanne, primary, Loux, Valentin, additional, Hennequet-Antier, Christelle, additional, Chambellon, Emilie, additional, Deschamps, Julien, additional, Trotereau, Angélina, additional, Furlan, Sylviane, additional, Darrigo, Claire, additional, Kempf, Florent, additional, Lao, Julie, additional, Milhes, Marine, additional, Roques, Céline, additional, Quinquis, Benoit, additional, Vandecasteele, Céline, additional, Boyer, Roxane, additional, Bouchez, Olivier, additional, Repoila, Francis, additional, Le Guennec, Jean, additional, Chiapello, Hélène, additional, Briandet, Romain, additional, Helloin, Emmanuelle, additional, Schouler, Catherine, additional, Kempf, Isabelle, additional, and Serror, Pascale, additional

Published
2022
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20. In vitromodelling of oral microbial invasion in the human colon

Author

Etienne-Mesmin, Lucie, primary, Meslier, Victoria, additional, Uriot, Ophélie, additional, Fournier, Elora, additional, Deschamps, Charlotte, additional, Denis, Sylvain, additional, David, Aymeric, additional, Jegou, Sarah, additional, Morabito, Christian, additional, Quinquis, Benoit, additional, Thirion, Florence, additional, Oñate, Florian Plaza, additional, Le Chatelier, Emmanuelle, additional, Ehrlich, S. Dusko, additional, Blanquet-Diot, Stéphanie, additional, and Almeida, Mathieu, additional

Published
2022
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21. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity:effect of biotin and prebiotic supplementation on improved metabolism

Author

Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, Clement, Karine, Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, and Clement, Karine

Published
2022

22. Dietary intervention impact on gut microbial gene richness

Author

Cotillard, Aurelie, Kennedy, Sean P., Kong, Ling Chun, Prifti, Edi, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Levenez, Florence, Galleron, Nathalie, Gougis, Sophie, Rizkalla, Salwa, Batto, Jean-Michel, Renault, Pierre, Dore, Joel, Zucker, Jean-Daniel, Clement, Karine, and Ehrlich, Stanislav Dusko

Subjects
Microbiota (Symbiotic organisms) -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Complex gene-environment interactions are considered important in the development of obesity (1). The composition of the gut microbiota can determine the efficacy of energy harvest from food (2-4) and changes [...]

Published
2013

23. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Bel Lassen, Pierre, Nielsen, Trine, Bergh, Per-Olof, Rouault, Christine, André, Sébastien, Marquet, Florian, Andreelli, Fabrizio, Salem, Joe-Elie, Assmann, Karen, Bastard, Jean-Philippe, Forslund, Sofia, Le Chatelier, Emmanuelle, Falony, Gwen, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Vieira-Silva, Sara, Hansen, Tue, Pedersen, Helle Krogh, Lewinter, Christian, Sønderskov, Nadja, Vestergaard, Henrik, Raes, Jeroen, Nielsen, Jens, Bork, Peer, Ehrlich, S. Dusko, Pedersen, Oluf, Aron-Wisneswky, Judith, Clément, Karine, Bäckhed, Fredrik, Molinaro, Antonio, Lassen, Pierre, Henricsson, Marcus, Wu, Hao, Adriouch, Solia, Belda, Eugeni, Chakaroun, Rima, Nielse, Trine, Bergh, Christine, Rouault, Sébastien, Andr, Florian, Marquet, Fabrizio, Andreelli, Joe-Elie, Salem, Karen, Assmann, Jean-Philippe, Bastard, Sofia, Forslund, Emmanuelle, Le Chatelier, Gwen, Falon, Nicolas, Pons, Edi, Prift, Benoit, Quinquis, Hugo, Roume, Sara, Vieira-Silv, Tue, Hansen, Krogh, Pedersen, Christian, Lewinter, Nadja, The, Metacardis, Køber, Lars, Vestergaar, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Galan, Pilar, Dumas, Marc-Emmanuel, Rae, Jeroen, Oppert, Jean-Michel, Letunic, Ivica, Nielse, Jens, Ehrlic, S, Stumvoll, Michael, Pederse, Oluf, Aron-Wisnewsky, Judith, Bäckhe, Fredrik, Sahlgrenska Center for Cardiovascular and Metabolic Research, Partenaires INRAE, Sahlgrenska University Hospital, 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), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, 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), Medical Department III – Endocrinology, Nephrology, Rheumatology, Universität Leipzig [Leipzig], Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre d'Investigation Clinique de Paris Est, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Tenon [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Experimental and Clinical Research Center [Berlin, Germany], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Université Catholique de Louvain (UCL), VIB-KU Leuven Center for Microbiology [Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), 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]), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Metabolism, Digestion and Reproduction, Imperial College London, National Heart and Lung Institute [London] (NHLI), Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), Biobyte Solutions GMBH, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Sahlgrenska Academy at University of Gothenburg [Göteborg], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rega Institute for Medical Research [Leuven, België], 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), CHU Pitié-Salpêtrière [AP-HP], 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], 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]), Chalmers University of Technology [Göteborg], European Molecular Biology Laboratory [Heidelberg] (EMBL), 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), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, HAL-SU, Gestionnaire, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord-Institut National Agronomique Paris-Grignon (INA P-G)-Sorbonne Université (SU)-CETAF-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD [France-Nord])-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)-Université de Yaoundé I-Sorbonne Université (SU), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Auteur indépendant, Commission of the European Communities, and Universität Leipzig

Subjects
0301 basic medicine, Male, ACCURATE METHOD, endocrine system diseases, Metabolite, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Type 2 diabetes, GUT MICROBIOME, GLUCOSE, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, [CHIM] Chemical Sciences, Prediabetes, lcsh:Science, 2. Zero hunger, RISK, Multidisciplinary, biology, INSULIN SENSITIVITY, Imidazoles, HOMEOSTASIS MODEL ASSESSMENT, Middle Aged, 3. Good health, Multidisciplinary Sciences, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Enterotype, Female, Adult, medicine.medical_specialty, Science, Carbohydrate metabolism, Microbiology, digestive system, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, INTESTINAL MICROBIOTA, Internal medicine, medicine, Humans, [CHIM]Chemical Sciences, Histidine, Author Correction, PHYSIOLOGY, Aged, Science & Technology, Bacteria, General Chemistry, Metabolism, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, MetaCardis Consortium, METAGENOME, INDIVIDUALS, 030104 developmental biology, chemistry, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, lcsh:Q, Bacteroides
Abstract

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism., Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Published
2020

24. Long inverted repeats around the chromosome replication terminus in the model strain Bacillus thuringiensis serovar israelensis BGSC 4Q7

Author

Bolotin, Alexander, Quinquis, Benoit, Roume, Hugo, Gohar, Michel, Lereclus, Didier, and Sorokin, Alexei

Subjects
DNA Replication, BGSC strains, Whole Genome Sequencing, Prophages, replication termination, Inverted Repeat Sequences, Bacillus thuringiensis, High-Throughput Nucleotide Sequencing, Chromosomes, Bacterial, Serogroup, plasmid-chromosome association, chromosome structure, Microbial evolution and epidemiology: Mechanisms of evolution, Selection, Genetic, long inverted repeats, Research Article, Plasmids
Abstract

Bacillus thuringiensis serovar israelensis is the most widely used natural biopesticide against mosquito larvae worldwide. Its lineage has been actively studied and a plasmid-free strain, B . thuringiensis serovar israelensis BGSC 4Q7 (4Q7), has been produced. Previous sequencing of the genome of this strain has revealed the persistent presence of a 235 kb extrachromosomal element, pBtic235, which has been shown to be an inducible prophage, although three putative chromosomal prophages have been lost. Moreover, a 492 kb region, potentially including the standard replication terminus, has also been deleted in the 4Q7 strain, indicating an absence of essential genes in this area. We reanalysed the genome coverage distribution of reads for the previously sequenced variant strain, and sequenced two independently maintained samples of the 4Q7 strain. A 553 kb area, close to the 492 kb deletion, was found to be duplicated. This duplication presumably restored the equal sizes of the replichores, and a balanced functioning of replication termination. An analysis of genome assembly graphs revealed a transient association of the host chromosome with the pBtic235 element. This association may play a functional role in the replication of the bacterial chromosome, and the termination of this process in particular. The genome-restructuring events detected may modify the genetic status of cytotoxic or haemolytic toxins, potentially influencing strain virulence. Twelve of the single-nucleotide variants identified in 4Q7 were probably due to the procedure used for strain construction or were present in the precursor of this strain. No sequence variants were found in pBtic235, but the distribution of the corresponding 4Q7 reads indicates a significant difference from counterparts in natural B. thuringiensis serovar israelensis strains, suggesting a duplication or over-replication in 4Q7. Thus, the 4Q7 strain is not a pure plasmid-less offshoot, but a highly genetically modified derivative of its natural ancestor. In addition to potentially influencing virulence, genome-restructuring events can modify the replication termination machinery. These findings have potential implications for the conclusions of virulence studies on 4Q7 as a model, but they also raise interesting fundamental questions about the functioning of the Bacillus genome.

Published
2020

25. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Author

Vieira-Silva, Sara, Falony, Gwen, Belda, Eugeni, Nielsen, Trine, Aron-Wisnewsky, Judith, Chakaroun, Rima, Forslund, Sofia K, Assmann, Karen, Valles-Colomer, Mireia, Nguyen, Thi Thuy Duyen, Proost, Sebastian, Prifti, Edi, Tremaroli, Valentina, Pons, Nicolas, Le Chatelier, Emmanuelle, Andreelli, Fabrizio, Bastard, Jean-Phillippe, Coelho, Luis Pedro, Galleron, Nathalie, Hansen, Tue H, Hulot, Jean-Sébastien, Lewinter, Christian, Pedersen, Helle K, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Søndertoft, Nadja B, Touch, Sothea, Dumas, Marc-Emmanuel, Ehrlich, Stanislav Dusko, Galan, Pilar, Gøtze, Jens P, Hansen, Torben, Holst, Jens J, Køber, Lars, Letunic, Ivica, Nielsen, Jens, Oppert, Jean-Michel, Stumvoll, Michael, Vestergaard, Henrik, Zucker, Jean-Daniel, Bork, Peer, Pedersen, Oluf, Bäckhed, Fredrik, Clément, Karine, Raes, Jeroen, Vieira-Silva, Sara, Falony, Gwen, Belda, Eugeni, Nielsen, Trine, Aron-Wisnewsky, Judith, Chakaroun, Rima, Forslund, Sofia K, Assmann, Karen, Valles-Colomer, Mireia, Nguyen, Thi Thuy Duyen, Proost, Sebastian, Prifti, Edi, Tremaroli, Valentina, Pons, Nicolas, Le Chatelier, Emmanuelle, Andreelli, Fabrizio, Bastard, Jean-Phillippe, Coelho, Luis Pedro, Galleron, Nathalie, Hansen, Tue H, Hulot, Jean-Sébastien, Lewinter, Christian, Pedersen, Helle K, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Søndertoft, Nadja B, Touch, Sothea, Dumas, Marc-Emmanuel, Ehrlich, Stanislav Dusko, Galan, Pilar, Gøtze, Jens P, Hansen, Torben, Holst, Jens J, Køber, Lars, Letunic, Ivica, Nielsen, Jens, Oppert, Jean-Michel, Stumvoll, Michael, Vestergaard, Henrik, Zucker, Jean-Daniel, Bork, Peer, Pedersen, Oluf, Bäckhed, Fredrik, Clément, Karine, and Raes, Jeroen

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 humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 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

Published
2020

26. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Molinaro, Antonio, Bel Lassen, Pierre, Henricsson, Marcus, Wu, Hao, Adriouch, Solia, Belda, Eugeni, Chakaroun, Rima, Nielsen, Trine, Bergh, Per-Olof, Rouault, Christine, Andre, Sebastien, Marquet, Florian, Andreelli, Fabrizio, Salem, Joe-Elie, Assmann, Karen, Bastard, Jean-Philippe, Forslund, Sofia, Le Chatelier, Emmanuelle, Falony, Gwen, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Vieira-Silva, Sara, Hansen, Tue H., Pedersen, Helle Krogh, Lewinter, Christian, Sønderskov, Nadja B., Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Galan, Pilar, Dumas, Marc-Emmanuel, Raes, Jeroen, Oppert, Jean-Michel, Letunic, Ivica, Nielsen, Jens, Bork, Peer, Ehrlich, S. Dusko, Stumvoll, Michael, Pedersen, Oluf, Aron-Wisneswky, Judith, Clement, Karine, Baeckhed, Fredrik, Molinaro, Antonio, Bel Lassen, Pierre, Henricsson, Marcus, Wu, Hao, Adriouch, Solia, Belda, Eugeni, Chakaroun, Rima, Nielsen, Trine, Bergh, Per-Olof, Rouault, Christine, Andre, Sebastien, Marquet, Florian, Andreelli, Fabrizio, Salem, Joe-Elie, Assmann, Karen, Bastard, Jean-Philippe, Forslund, Sofia, Le Chatelier, Emmanuelle, Falony, Gwen, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Vieira-Silva, Sara, Hansen, Tue H., Pedersen, Helle Krogh, Lewinter, Christian, Sønderskov, Nadja B., Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Galan, Pilar, Dumas, Marc-Emmanuel, Raes, Jeroen, Oppert, Jean-Michel, Letunic, Ivica, Nielsen, Jens, Bork, Peer, Ehrlich, S. Dusko, Stumvoll, Michael, Pedersen, Oluf, Aron-Wisneswky, Judith, Clement, Karine, and Baeckhed, Fredrik

Abstract

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism. Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Published
2020

27. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

Author

Meslier, Victoria, Laiola, Manolo, Roager, Henrik Munch, De Filippis, Francesca, Roume, Hugo, Quinquis, Benoit, Giacco, Rosalba, Mennella, Ilario, Ferracane, Rosalia, Pons, Nicolas, Pasolli, Edoardo, Rivellese, Angela, Dragsted, Lars Ove, Vitaglione, Paola, Ehrlich, Stanislav Dusko, Ercolini, Danilo, Meslier, Victoria, Laiola, Manolo, Roager, Henrik Munch, De Filippis, Francesca, Roume, Hugo, Quinquis, Benoit, Giacco, Rosalba, Mennella, Ilario, Ferracane, Rosalia, Pons, Nicolas, Pasolli, Edoardo, Rivellese, Angela, Dragsted, Lars Ove, Vitaglione, Paola, Ehrlich, Stanislav Dusko, and Ercolini, Danilo

Abstract

Objectives: This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.Design: Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.Results: Increased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.Conclusion: Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.

Published
2020

28. Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin

Author

Bolotin, Alexander, Quinquis, Benoit, Sorokin, Alexei, and Ehrlich, S. Dusko

Subjects
Genomes -- Research, Prokaryotes -- Genetic aspects, Biological sciences
Abstract

Numerous prokaryote genomes contain structures known as clustered regularly interspaced short palindromic repeats (CRISPRs), composed of 25-50 bp repeats separated by unique sequence spacers of similar length. CRISPR structures are found in the vicinity of four genes named cas 1 to cas4. In silico analysis revealed another cluster of three genes associated with CRISPR structures in many bacterial species, named here as cas1B, cas5 and cas6, and also revealed a certain number of spacers that have homology with extant genes, most frequently derived from phages, but also derived from other extrachromosomal elements. Sequence analysis of CRISPR structures from 24 strains of Streptococcus thermophilus and Streptococcus vestibularis confirmed the homology of spacers with extrachromosomal elements. Phage sensitivity of S. thermophilus strains appears to be correlated with the number of spacers in the CRISPR locus the strain carries. The authors suggest that the spacer elements are the traces of past invasions by extrachromosomal elements, and hypothesize that they provide the cell immunity against phage infection, and more generally foreign DNA expression, by coding an anti-sense RNA. The presence of gene fragments in CRISPR structures and the nuclease motifs in cas genes of both cluster types suggests that CRISPR formation involves a DNA degradation step.

Published
2005

29. Recent genetic transfer between Lactococcus lactis and enterobacteria

Author

Bolotin, Alexander, Quinquis, Benoit, Sorokin, Alexei, and Ehrlich, Dusko S.

Subjects
Lactococcus -- Research, Lactococcus -- Genetic aspects, Enterobacter -- Research, Enterobacter -- Genetic aspects, Enterobacteriaceae -- Research, Enterobacteriaceae -- Genetic aspects, Bacteriology -- Research, Biological sciences
Abstract

The genome sequence of Lactococcus lactis revealed that the ycdB gene was recently exchanged between lactococci and enterobacteria. The present study of ycdB orthologs suggests that L. lactis was probably the gene donor and reveals three instances of gene transfer to enterobacteria. Analysis of ycdB gene transfer between two L. lactis subspecies, L. lactis subsp, lactis and L. lactis subsp, cremoris, indicates that the gene can be mobilized, possibly by conjugation.

Published
2004

30. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

Author

Meslier, Victoria, primary, Laiola, Manolo, additional, Roager, Henrik Munch, additional, De Filippis, Francesca, additional, Roume, Hugo, additional, Quinquis, Benoit, additional, Giacco, Rosalba, additional, Mennella, Ilario, additional, Ferracane, Rosalia, additional, Pons, Nicolas, additional, Pasolli, Edoardo, additional, Rivellese, Angela, additional, Dragsted, Lars Ove, additional, Vitaglione, Paola, additional, Ehrlich, Stanislav Dusko, additional, and Ercolini, Danilo, additional

Published
2020
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31. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Author

Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E, Prifti, Edi, Aron-Wisnewsky, Judith, Debédat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloé, André, Sébastien, Andreelli, Fabrizio, Blu¨her, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H, Holmes, Bridget, Ji, Boyang, Krogh Pedersen, Helle, Le, Phuong, Le Chatelier, Emmanuelle, Lewinter, Christian, Mannerås-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B, Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Ba¨ckhed, Fredrik, Raes, Jeroen, and Clément, Karine

Abstract

ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

Published
2022
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32. Identification of New Factors Modulating Adhesion Abilities of the Pioneer Commensal Bacterium Streptococcus salivarius

Author

Couvigny, Benoit, primary, Kulakauskas, Saulius, additional, Pons, Nicolas, additional, Quinquis, Benoit, additional, Abraham, Anne-Laure, additional, Meylheuc, Thierry, additional, Delorme, Christine, additional, Renault, Pierre, additional, Briandet, Romain, additional, Lapaque, Nicolas, additional, and Guédon, Eric, additional

Published
2018
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33. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome

Author

Shoaie, Saeed, Ghaffari, Pouyan, Kovatcheva-Datchary, Petia, Mardinoglu, Adil, Sen, Partho, Pujos-Guillot, Estelle, De Wouters, Tomas, Juste, Catherine, Rizkalla, Salwa, Chilloux, Julien, Hoyles, Lesley, Nicholson, Jeremy K., Consortium, MICRO-Obes, Doré, Joël, Dumas, Marc E., Clément, Karine, Bäckhed, Fredrik, Nielsen, Jens, Kennedy, Sean P., Prifti, Edi, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Levenez, Florence, Galleron, Nathalie, Batto, Jean-Michel, Ehrlich, Stanislav, Blottiere, Herve, Lepage, Patricia, Maguin, Emmanuelle, Van De Guchte, Maarten, Department of Biology and Biological Engineering, Chalmers University of Technology [Göteborg], University of Gothenburg (GU), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Plateforme d'Exploration du Métabolisme, Institut National de la Recherche Agronomique (INRA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MetaGenoPolis, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imperial College London, University of Copenhagen = Københavns Universitet (KU), Département Microbiologie et Chaîne Alimentaire (MICA), Knut and Alice Wallenberg Foundation, Bill & Melinda Gates Foundation, Torsten Soderbergs Stiftelse, European Commission HEALTH-F4-2012-305312, Fondation Coeur et Arteres, French National Agency of Research (ANR MicroObes and 'Investissements d'avenir') ANR-10-IAHU-05, ProdInra, Migration, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 Copenhagen = Københavns Universitet (UCPH), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Commission of the European Communities, and Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, HOST, Interactive optimization, Physiology, Genome scale, Microbial metabolism, Computational biology, Gut flora, Bioinformatics, Models, Biological, MICROFLORA, Endocrinology & Metabolism, RECONSTRUCTIONS, 03 medical and health sciences, 0302 clinical medicine, Human gut, MICRO-Obes Consortium, 1101 Medical Biochemistry And Metabolomics, Humans, Metabolic modeling, AMINO-ACIDS, Microbiome, Intestinal Mucosa, Molecular Biology, Feces, 030304 developmental biology, 0303 health sciences, Science & Technology, biology, Microbiota, 0601 Biochemistry And Cell Biology, Cell Biology, biology.organism_classification, GENE, Intestines, PROTEIN-COUPLED RECEPTOR, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, CHAIN FATTY-ACIDS, HUMAN LARGE-INTESTINE, BACTERIA, Female, ADIPOSITY, Life Sciences & Biomedicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

International audience; The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention.

Published
2015

34. Characterization of the gut microbiota by quantitative metagenomics: a promising tool for risk stratification in NAFLD patients

Author

Ratziu, V., Pichaud, M., Fedchuk, L., Levenez, Florence, Quinquis, Benoit, Galleron, Nathalie, Batto, Jean-Michel, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Kennedy, Sean, Doré, Joël, Ehrlich, Stanislav, Rimbaud, P., CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Enterome Bioscience, Association Recherche Maladies Hépatiques Virales, Partenaires INRAE, MetaGenoPolis, and Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio], nafld, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013

35. Erratum: Corrigendum: Dietary intervention impact on gut microbial gene richness

Author

Cotillard, Aurélie, primary, Kennedy, Sean P., additional, Kong, Ling Chun, additional, Prifti, Edi, additional, Pons, Nicolas, additional, Le Chatelier, Emmanuelle, additional, Almeida, Mathieu, additional, Quinquis, Benoit, additional, Levenez, Florence, additional, Galleron, Nathalie, additional, Gougis, Sophie, additional, Rizkalla, Salwa, additional, Batto, Jean-Michel, additional, Renault, Pierre, additional, consortium, ANR MicroObes, additional, Doré, Joel, additional, Zucker, Jean-Daniel, additional, Clément, Karine, additional, and Ehrlich, Stanislav Dusko, additional

Published
2013
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38. Genotypic and phenotypic characterization of Lactobacillus plantarurn strains isolated from Thai fermented fruits and vegetables.

Author

Tanganurat, Winee, Quinquis, Benoit, Leelawatcharamas, Vichien, and Bolotin, Alexander

Subjects
LACTIC acid bacteria genetics, FRUIT research, VEGETABLES, FERMENTATION, RAW materials, NUCLEOTIDE sequence
Abstract

The article discusses a study that aims to characterize and distinguish the 10 isolates of lactic acid bacterium (LAB) from fermented fruits and vegetables. The researchers used fruits and vegetables including cabbage, garlic, and mango as raw materials for fermentation. Accordingly, various processes were applied including phenotypic characterization, chromosomal DNA isolation, and multilocus sequence typing (MLST) analysis. The results show three various allelic combinations on the isolates.

Published
2009
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39. Elevated serum ceramides are linked with obesity-associated gut dysbiosis and impaired glucose metabolism.

Author

Kayser, Brandon D., Prifti, Edi, Lhomme, Marie, Belda, Eugeni, Dao, Maria-Carlota, Aron-Wisnewsky, Judith, MICRO-Obes Consortium, Cotillard, Aurélie, Kennedy, Sean P., Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Galleron, Nathalie, Batto, Jean-Michel, Renault, Pierre, Ehrlich, Stanislav Dusko, Blottière, Hervé, Leclerc, Marion, and de Wouters, Tomas

Subjects
CERAMIDES, GLUCOSE metabolism, LIPID metabolism disorders, GUT microbiome, SHOTGUN sequencing, LIPID metabolism
Abstract

Introduction: Low gut microbiome richness is associated with dyslipidemia and insulin resistance, and ceramides and other sphingolipids are implicated in the development of diabetes. Objectives: Determine whether circulating sphingolipids, particularly ceramides, are associated with alterations in the gut microbiome among obese patients with increased diabetes risk. Methods: This was a cross-sectional and longitudinal retrospective analysis of a dietary/weight loss intervention. Fasted serum was collected from 49 participants (41 women) and analyzed by HPLC–MS/MS to quantify 45 sphingolipids. Shotgun metagenomic sequencing of stool was performed to profile the gut microbiome. Results: Confirming the link to deteriorated glucose homeostasis, serum ceramides were positively correlated with fasting glucose, but inversely correlated with fasting and OGTT-derived measures of insulin sensitivity and β-cell function. Significant associations with gut dysbiosis were demonstrated, with SM and ceramides being inversely correlated with gene richness. Ceramides with fatty acid chain lengths of 20–24 carbons were the most associated with low richness. Diet-induced weight loss, which improved gene richness, decreased most sphingolipids. Thirty-one MGS, mostly corresponding to unidentified bacteria species, were inversely correlated with ceramides, including a number of Bifidobacterium and Methanobrevibacter smithii. Higher ceramide levels were also associated with increased metagenomic modules for lipopolysaccharide synthesis and flagellan synthesis, two pathogen-associated molecular patterns, and decreased enrichment of genes involved in methanogenesis and bile acid metabolism. Conclusion: This study identifies an association between gut microbiota richness, ceramides, and diabetes risk in overweight/obese humans, and suggests that the gut microbiota may contribute to dysregulation of lipid metabolism in metabolic disorders. [ABSTRACT FROM AUTHOR]

Published
2019
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40. Complete Genome Sequence of Lactococcus lactis subsp. cremoris A76.

Author

Bolotin, Alexander, Quinquis, Benoit, Ehrlich, Stanislas Dusko, and Sorokin, Alexei

Subjects
*LACTOCOCCUS lactis, *CHEESE, *GENOMES, *GENETICS, *STREPTOCOCCUS
Abstract

We report the complete genome sequence of Lactococcus lactis subsp, cremoris A76, a dairy strain isolated from a cheese production outfit. Genome analysis detected two contiguous islands fitting to the L. lactis subsp. iactis rather than to the L. lactis subsp. cremoris lineage. This indicates the existence of genetic exchange between the diverse subspecies, presumably related to the technological process. [ABSTRACT FROM AUTHOR]

Published
2012
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41. Corrigendum: Dietary intervention impact on gut microbial gene richness.

Author

Cotillard, Aurélie, Kennedy, Sean P., Kong, Ling Chun, Prifti, Edi, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Levenez, Florence, Galleron, Nathalie, Gougis, Sophie, Rizkalla, Salwa, Batto, Jean-Michel, Renault, Pierre, consortium, ANR MicroObes, Doré, Joel, Zucker, Jean-Daniel, Clément, Karine, and Ehrlich, Stanislav Dusko

Subjects
NUTRITION counseling, MICROBIAL genes
Abstract

A correction to the article "Dietary intervention impact on gut microbial gene richness" that was published in a 2013 issue is presented.

Published
2013
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42. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

Author

Lars O. Dragsted, Danilo Ercolini, Ilario Mennella, Francesca De Filippis, Hugo Roume, Stanislav Dusko Ehrlich, Benoit Quinquis, Angela A. Rivellese, Henrik Munch Roager, Manolo Laiola, Nicolas Pons, Edoardo Pasolli, Paola Vitaglione, Victoria Meslier, Rosalia Ferracane, Rosalba Giacco, Meslier, Victoria, Laiola, Manolo, Roager, Henrik Munch, De Filippis, Francesca, Roume, Hugo, Quinquis, Benoit, Giacco, Rosalba, Mennella, Ilario, Ferracane, Rosalia, Pons, Nicola, Pasolli, Edoardo, Rivellese, Angela, Dragsted, Lars Ove, Vitaglione, Paola, Ehrlich, Stanislav Dusko, and Ercolini, Danilo

Subjects
0301 basic medicine, 030109 nutrition & dietetics, Mediterranean diet, biology, business.industry, Gastroenterology, Physiology, Faecalibacterium prausnitzii, intestinal microbiology, Overweight, Systemic inflammation, biology.organism_classification, 03 medical and health sciences, nutrition, 030104 developmental biology, medicine, Metabolome, diet, Microbiome, Carnitine, medicine.symptom, business, Sedentary lifestyle, medicine.drug
Abstract

ObjectivesThis study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.DesignEighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.ResultsIncreased MD adherence in the MedD group successfully reprogrammed subjects’ intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.ConclusionSwitching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.

Published
2020

43. Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.

Author

Molinaro A, Bel Lassen P, Henricsson M, Wu H, Adriouch S, Belda E, Chakaroun R, Nielsen T, Bergh PO, Rouault C, André S, Marquet F, Andreelli F, Salem JE, Assmann K, Bastard JP, Forslund S, Le Chatelier E, Falony G, Pons N, Prifti E, Quinquis B, Roume H, Vieira-Silva S, Hansen TH, Pedersen HK, Lewinter C, Sønderskov NB, Køber L, Vestergaard H, Hansen T, Zucker JD, Galan P, Dumas ME, Raes J, Oppert JM, Letunic I, Nielsen J, Bork P, Ehrlich SD, Stumvoll M, Pedersen O, Aron-Wisnewsky J, Clément K, and Bäckhed F

Published
2020
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44. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.

Author

Molinaro A, Bel Lassen P, Henricsson M, Wu H, Adriouch S, Belda E, Chakaroun R, Nielsen T, Bergh PO, Rouault C, André S, Marquet F, Andreelli F, Salem JE, Assmann K, Bastard JP, Forslund S, Le Chatelier E, Falony G, Pons N, Prifti E, Quinquis B, Roume H, Vieira-Silva S, Hansen TH, Pedersen HK, Lewinter C, Sønderskov NB, Køber L, Vestergaard H, Hansen T, Zucker JD, Galan P, Dumas ME, Raes J, Oppert JM, Letunic I, Nielsen J, Bork P, Ehrlich SD, Stumvoll M, Pedersen O, Aron-Wisnewsky J, Clément K, and Bäckhed F

Subjects
Adult, Aged, Bacteria classification, Bacteria genetics, Bacteria isolation & purification, Bacteria metabolism, Cohort Studies, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 metabolism, Female, Histidine metabolism, Humans, Male, Middle Aged, Diabetes Mellitus, Type 2 microbiology, Gastrointestinal Microbiome, Imidazoles blood
Abstract

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.

Published
2020
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45. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.

Author

Vieira-Silva S, Falony G, Belda E, Nielsen T, Aron-Wisnewsky J, Chakaroun R, Forslund SK, Assmann K, Valles-Colomer M, Nguyen TTD, Proost S, Prifti E, Tremaroli V, Pons N, Le Chatelier E, Andreelli F, Bastard JP, Coelho LP, Galleron N, Hansen TH, Hulot JS, Lewinter C, Pedersen HK, Quinquis B, Rouault C, Roume H, Salem JE, Søndertoft NB, Touch S, Dumas ME, Ehrlich SD, Galan P, Gøtze JP, Hansen T, Holst JJ, Køber L, Letunic I, Nielsen J, Oppert JM, Stumvoll M, Vestergaard H, Zucker JD, Bork P, Pedersen O, Bäckhed F, Clément K, and Raes J

Subjects
Bacteroides isolation & purification, Cohort Studies, Cross-Sectional Studies, Faecalibacterium isolation & purification, Feces microbiology, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Inflammatory Bowel Diseases microbiology, Male, Obesity microbiology, Prevalence, Dysbiosis epidemiology, Dysbiosis prevention & control, Gastrointestinal Microbiome drug effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
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 1,2 . Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities 1,2 , and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease 2 . Reported changes in stool consistency 3 and inflammation status 4 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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