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2. Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome

Author

Derosa, Lisa, Iebba, Valerio, Silva, Carolina Alves Costa, Piccinno, Gianmarco, Wu, Guojun, Lordello, Leonardo, Routy, Bertrand, Zhao, Naisi, Thelemaque, Cassandra, Birebent, Roxanne, Marmorino, Federica, Fidelle, Marine, Messaoudene, Meriem, Thomas, Andrew Maltez, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Sibilot, Denis Moro, Goldwasser, François, Scherpereel, Arnaud, Pegliasco, Hervé, Ghiringhelli, François, Bouchard, Nicole, Sow, Cissé, Darik, Ines, Zoppi, Silvia, Ly, Pierre, Reni, Anna, Daillère, Romain, Deutsch, Eric, Lee, Karla A., Bolte, Laura A., Björk, Johannes R., Weersma, Rinse K., Barlesi, Fabrice, Padilha, Lucas, Finzel, Ana, Isaksen, Morten L., Escudier, Bernard, Albiges, Laurence, Planchard, David, André, Fabrice, Cremolini, Chiara, Martinez, Stéphanie, Besse, Benjamin, Zhao, Liping, Segata, Nicola, Wojcik, Jérôme, Kroemer, Guido, and Zitvogel, Laurence

Published
2024
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4. WED-540-YI Gender-dependent HCC development in X/MYC mouse model

Author

Alfano, Vincenzo, primary, Paturel, Alexia, additional, Iebba, Valerio, additional, Canarutto, Giulia, additional, Cocca, Massimiliano, additional, Lombard, Alice, additional, De Nicola, Francesca, additional, Faivre, Jamila, additional, Piazza, Silvano, additional, Levrero, Massimo, additional, Caron de Fromentel, Claude, additional, and Guerrieri, Francesca, additional

Published
2024
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5. Short-chain fatty acids promote the effect of environmental signals on the gut microbiome and metabolome in mice

Author

Marrocco, Francesco, Delli Carpini, Mary, Garofalo, Stefano, Giampaoli, Ottavia, De Felice, Eleonora, Di Castro, Maria Amalia, Maggi, Laura, Scavizzi, Ferdinando, Raspa, Marcello, Marini, Federico, Tomassini, Alberta, Nicolosi, Roberta, Cason, Carolina, Trettel, Flavia, Miccheli, Alfredo, Iebba, Valerio, D’Alessandro, Giuseppina, and Limatola, Cristina

Published
2022
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6. Does gut microbiota dysbiosis impact the metabolic alterations of hydrogen sulfide and lanthionine in patients with chronic kidney disease?

Author

Garcia-Martinez, Yuselys, Alexandrova, Elena, Iebba, Valerio, Ferravante, Carlo, Spinelli, Michelle, Franci, Gianluigi, Amoresano, Angela, Weisz, Alessandro, Trepiccione, Francesco, Borriello, Margherita, Ingrosso, Diego, and Perna, Alessandra F.

Abstract

Background: Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to H2S and lanthionine metabolic alterations in CKD. Methods: The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16 S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively. Results: The CKD population exhibited a tenfold increase in serum lanthionine associated with kidney dysfunction. Despite lanthionine retention, hemodialysis and transplant patients had significantly lower serum H2S than healthy controls. Fecal H2S levels were not altered or related to bloodstream H2S concentrations. Conversely, fecal lanthionine was significantly increased in CKD compared to healthy controls and associated with kidney dysfunction. Microbiota composition varied among CKD groups and healthy controls, with the greatest dissimilarity observed between hemodialysis and transplant patients. Changes relative to the healthy group included uneven Ruminococcus gnavus distribution (higher in transplant patients and lower in non-dialysis CKD patients), reduced abundance of the short-chain fatty acid-producing bacteria Alistipes indistinctus and Coprococcus eutactus among transplant patients, and depleted Streptococcus salivarius in non-dialysis CKD patients. A higher abundance of Methanobrevibacter smithii, Christensenella minuta, and Negativibacillus massiliensis differentiated hemodialysis patients from controls. No correlation was found between differentially abundant species and the metabolic profile that could account for the H2S and lanthionine alterations observed. Conclusions: The metabolic deregulation of H2S and lanthionine observed in the study was not associated with alterations in the gut microbiota composition in CKD patients. Further research on microbial sulfur pathways may provide a better understanding of the role of gut microbiota in maintaining H2S and lanthionine homeostasis. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Published
2022
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8. Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment

Author

Terrisse, Safae, Derosa, Lisa, Iebba, Valerio, Ghiringhelli, François, Vaz-Luis, Ines, Kroemer, Guido, Fidelle, Marine, Christodoulidis, Stergios, Segata, Nicola, Thomas, Andrew Maltez, Martin, Anne-Laure, Sirven, Aude, Everhard, Sibille, Aprahamian, Fanny, Nirmalathasan, Nitharsshini, Aarnoutse, Romy, Smidt, Marjolein, Ziemons, Janine, Caldas, Carlos, Loibl, Sibylle, Denkert, Carsten, Durand, Sylvere, Iglesias, Claudia, Pietrantonio, Filippo, Routy, Bertrand, André, Fabrice, Pasolli, Edoardo, Delaloge, Suzette, and Zitvogel, Laurence

Published
2021
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9. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

Author

Andrews, Miles C., Duong, Connie P. M., Gopalakrishnan, Vancheswaran, Iebba, Valerio, Chen, Wei-Shen, Derosa, Lisa, and Khan, Md Abdul Wadud

Subjects
Microbiota (Symbiotic organisms) -- Health aspects, Immunotherapy -- Complications and side effects, Melanoma -- Development and progression -- Care and treatment, Biological sciences, Health
Abstract

Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any [greater than or equal to]grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1[beta] in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB. Clinical benefit or intestinal toxicity resulting from combined immune checkpoint blockade in patients with melanoma associates with prevalent commensal bacteria and can be decoupled by IL-1R inhibition., Author(s): Miles C. Andrews [sup.1] [sup.2] [sup.3] , Connie P. M. Duong [sup.4] [sup.5] [sup.6] , Vancheswaran Gopalakrishnan [sup.1] , Valerio Iebba [sup.4] [sup.5] , Wei-Shen Chen [sup.7] [sup.8] , [...]

Published
2021
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10. Multifaceted modes of action of the anticancer probiotic Enterococcus hirae

Author

Goubet, Anne-Gaëlle, Wheeler, Richard, Fluckiger, Aurélie, Qu, Bo, Lemaître, Fabien, Iribarren, Kristina, Mondragón, Laura, Tidjani Alou, Maryam, Pizzato, Eugénie, Durand, Sylvère, Derosa, Lisa, Aprahamian, Fanny, Bossut, Noélie, Moya-Nilges, Maryse, Derrien, Diane, Chen, Guo, Leduc, Marion, Joseph, Adrien, Pons, Nicolas, Le Chatelier, Emmanuelle, Segata, Nicola, Yonekura, Satoru, Iebba, Valerio, Kepp, Oliver, Raoult, Didier, André, Fabrice, Kroemer, Guido, Boneca, Ivo Gomperts, Zitvogel, Laurence, and Daillère, Romain

Published
2021
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11. Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients

Author

Picard, Marion, Yonekura, Satoru, Slowicka, Karolina, Petta, Ioanna, Rauber, Conrad, Routy, Bertrand, Richard, Corentin, Iebba, Valerio, Tidjani Alou, Maryam, Becharef, Sonia, Ly, Pierre, Pizzato, Eugenie, Lehmann, Christian H. K., Amon, Lukas, Klein, Christophe, Opolon, Paule, Gomperts Boneca, Ivo, Scoazec, Jean-Yves, Hollebecque, Antoine, Malka, David, Ghiringhelli, François, Dudziak, Diana, Berx, Geert, Vereecke, Lars, van Loo, Geert, Kroemer, Guido, Zitvogel, Laurence, and Roberti, Maria Paula

Published
2021
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12. Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer

Author

Roberti, Maria Paula, Yonekura, Satoru, Duong, Connie P. M., Picard, Marion, Ferrere, Gladys, Tidjani Alou, Maryam, Rauber, Conrad, Iebba, Valerio, Lehmann, Christian H. K., Amon, Lukas, Dudziak, Diana, Derosa, Lisa, Routy, Bertrand, Flament, Caroline, Richard, Corentin, Daillère, Romain, Fluckiger, Aurélie, Van Seuningen, Isabelle, Chamaillard, Mathias, Vincent, Audrey, Kourula, Stephanie, Opolon, Paule, Ly, Pierre, Pizzato, Eugénie, Becharef, Sonia, Paillet, Juliette, Klein, Christophe, Marliot, Florence, Pietrantonio, Filippo, Benoist, Stéphane, Scoazec, Jean-Yves, Dartigues, Peggy, Hollebecque, Antoine, Malka, David, Pagès, Franck, Galon, Jérôme, Gomperts Boneca, Ivo, Lepage, Patricia, Ryffel, Bernard, Raoult, Didier, Eggermont, Alexander, Vanden Berghe, Tom, Ghiringhelli, François, Vandenabeele, Peter, Kroemer, Guido, and Zitvogel, Laurence

Published
2020
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13. Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis

Author

Le Naour, Julie, primary, Montégut, Léa, additional, Pan, Yuhong, additional, Scuderi, Sarah Adriana, additional, Cordier, Pierre, additional, Joseph, Adrien, additional, Sauvat, Allan, additional, Iebba, Valerio, additional, Paillet, Juliette, additional, Ferrere, Gladys, additional, Brechard, Ludivine, additional, Mulot, Claire, additional, Dubourg, Grégory, additional, Zitvogel, Laurence, additional, Pol, Jonathan G., additional, Vacchelli, Erika, additional, Puig, Pierre-Laurent, additional, and Kroemer, Guido, additional

Published
2023
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15. Data from Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Yonekura, Satoru, primary, Terrisse, Safae, primary, Alves Costa Silva, Carolina, primary, Lafarge, Antoine, primary, Iebba, Valerio, primary, Ferrere, Gladys, primary, Goubet, Anne-Gaëlle, primary, Fahrner, Jean-Eudes, primary, Lahmar, Imran, primary, Ueda, Kousuke, primary, Mansouri, Gibrail, primary, Pizzato, Eugénie, primary, Ly, Pierre, primary, Mazzenga, Marine, primary, Thelemaque, Cassandra, primary, Fidelle, Marine, primary, Jaulin, Fanny, primary, Cartry, Jérôme, primary, Deloger, Marc, primary, Aglave, Marine, primary, Droin, Nathalie, primary, Opolon, Paule, primary, Puget, Angélique, primary, Mann, Fanny, primary, Neunlist, Michel, primary, Bessard, Anne, primary, Aymeric, Laetitia, primary, Matysiak-Budnik, Tamara, primary, Bosq, Jacques, primary, Hofman, Paul, primary, Duong, Connie P.M., primary, Ugolini, Sophie, primary, Quiniou, Valentin, primary, Berrard, Sylvie, primary, Ryffel, Bernhard, primary, Kepp, Oliver, primary, Kroemer, Guido, primary, Routy, Bertrand, primary, Lordello, Leonardo, primary, Bani, Mohamed-Amine, primary, Segata, Nicola, primary, Yengej, Fjodor Yousef, primary, Clevers, Hans, primary, Scoazec, Jean-Yves, primary, Pasolli, Edoardo, primary, Derosa, Lisa, primary, and Zitvogel, Laurence, primary

Published
2023
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16. Supplementary Figure from Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Yonekura, Satoru, primary, Terrisse, Safae, primary, Alves Costa Silva, Carolina, primary, Lafarge, Antoine, primary, Iebba, Valerio, primary, Ferrere, Gladys, primary, Goubet, Anne-Gaëlle, primary, Fahrner, Jean-Eudes, primary, Lahmar, Imran, primary, Ueda, Kousuke, primary, Mansouri, Gibrail, primary, Pizzato, Eugénie, primary, Ly, Pierre, primary, Mazzenga, Marine, primary, Thelemaque, Cassandra, primary, Fidelle, Marine, primary, Jaulin, Fanny, primary, Cartry, Jérôme, primary, Deloger, Marc, primary, Aglave, Marine, primary, Droin, Nathalie, primary, Opolon, Paule, primary, Puget, Angélique, primary, Mann, Fanny, primary, Neunlist, Michel, primary, Bessard, Anne, primary, Aymeric, Laetitia, primary, Matysiak-Budnik, Tamara, primary, Bosq, Jacques, primary, Hofman, Paul, primary, Duong, Connie P.M., primary, Ugolini, Sophie, primary, Quiniou, Valentin, primary, Berrard, Sylvie, primary, Ryffel, Bernhard, primary, Kepp, Oliver, primary, Kroemer, Guido, primary, Routy, Bertrand, primary, Lordello, Leonardo, primary, Bani, Mohamed-Amine, primary, Segata, Nicola, primary, Yengej, Fjodor Yousef, primary, Clevers, Hans, primary, Scoazec, Jean-Yves, primary, Pasolli, Edoardo, primary, Derosa, Lisa, primary, and Zitvogel, Laurence, primary

Published
2023
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19. Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis

Author

Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, and Zitvogel, Laurence

Abstract

Gut dysbiosis has been associated with intestinal and extra-intestinal malignancies but whether and how carcinogenesis drives compositional shifts of the microbiome to its own benefit remains an open conundrum. Here we show that malignant processes can cause ileal mucosa atrophy, with villous microvascular constriction associated with dominance of sympathetic over cholinergic signaling. Rapid onset of tumorigenesis induced a burst of Reg3y release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long lasting dysbiosis dominated by Gram positive Clostridium species. Pharmacological blockade of B-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin or co-housing of tumor bearers with tumor free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Cancer patients harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extra-intestinal malignancies requiring specific therapies.

Published
2022

20. Cancer Induces a Stress Ileopathy Depending on beta-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Nefro Vasculaire Geneeskunde, CMM, Cancer, Hubrecht Institute with UMC, Yonekura, Satoru, Terrisse, Safae, Silva, Carolina Alves Costa, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne Gaëlle, Fahrner, Jean Eudes, Lahmar, Imran, Ueda, Kousuke, Mansouri, Gibrail, Pizzato, Eugénie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jérôme, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angélique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P.M., Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed Amine, Segata, Nicola, Yengej, Fjodor Yousef, Clevers, Hans, Scoazec, Jean Yves, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Nefro Vasculaire Geneeskunde, CMM, Cancer, Hubrecht Institute with UMC, Yonekura, Satoru, Terrisse, Safae, Silva, Carolina Alves Costa, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne Gaëlle, Fahrner, Jean Eudes, Lahmar, Imran, Ueda, Kousuke, Mansouri, Gibrail, Pizzato, Eugénie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jérôme, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angélique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P.M., Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed Amine, Segata, Nicola, Yengej, Fjodor Yousef, Clevers, Hans, Scoazec, Jean Yves, Pasolli, Edoardo, Derosa, Lisa, and Zitvogel, Laurence

Published
2022

21. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in advanced non-small cell lung cancer patients

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Chatelier, Emmanuelle Le, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Subjects
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Humans, Immunologic Factors, Akkermansia, Immunotherapy, Article
Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) are needed. We previously reported in 100 NSCLC and kidney cancer patients that fecal Akkermansia muciniphila (Akk) correlated with ICI clinical success. The endpoint of this study was to prospectively validate the prognostic significance of fecal Akk in advanced NSCLC patients treated with first or second line ICI. We performed shotgun metagenomics-based microbiome profiling using two different pipelines in 338 NSCLC patients. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that could be useful for future studies as a tool to aid patient stratification.

Published
2022

22. Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Yonekura, Satoru, primary, Terrisse, Safae, additional, Alves Costa Silva, Carolina, additional, Lafarge, Antoine, additional, Iebba, Valerio, additional, Ferrere, Gladys, additional, Goubet, Anne-Gaëlle, additional, Fahrner, Jean-Eudes, additional, Lahmar, Imran, additional, Ueda, Kousuke, additional, Mansouri, Gibrail, additional, Pizzato, Eugénie, additional, Ly, Pierre, additional, Mazzenga, Marine, additional, Thelemaque, Cassandra, additional, Fidelle, Marine, additional, Jaulin, Fanny, additional, Cartry, Jérôme, additional, Deloger, Marc, additional, Aglave, Marine, additional, Droin, Nathalie, additional, Opolon, Paule, additional, Puget, Angélique, additional, Mann, Fanny, additional, Neunlist, Michel, additional, Bessard, Anne, additional, Aymeric, Laetitia, additional, Matysiak-Budnik, Tamara, additional, Bosq, Jacques, additional, Hofman, Paul, additional, Duong, Connie P.M., additional, Ugolini, Sophie, additional, Quiniou, Valentin, additional, Berrard, Sylvie, additional, Ryffel, Bernhard, additional, Kepp, Oliver, additional, Kroemer, Guido, additional, Routy, Bertrand, additional, Lordello, Leonardo, additional, Bani, Mohamed-Amine, additional, Segata, Nicola, additional, Yengej, Fjodor Yousef, additional, Clevers, Hans, additional, Scoazec, Jean-Yves, additional, Pasolli, Edoardo, additional, Derosa, Lisa, additional, and Zitvogel, Laurence, additional

Published
2021
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23. Profiling of Oral Microbiota and Cytokines in COVID-19 Patients

Author

Iebba, Valerio, primary, Zanotta, Nunzia, additional, Campisciano, Giuseppina, additional, Zerbato, Verena, additional, Di Bella, Stefano, additional, Cason, Carolina, additional, Luzzati, Roberto, additional, Confalonieri, Marco, additional, Palamara, Anna Teresa, additional, and Comar, Manola, additional

Published
2021
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24. Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis

Author

Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, and Zitvogel, Laurence

Abstract

Gut dysbiosis has been associated with intestinal and extra-intestinal malignancies but whether and how carcinogenesis drives compositional shifts of the microbiome to its own benefit remains an open conundrum. Here we show that malignant processes can cause ileal mucosa atrophy, with villous microvascular constriction associated with dominance of sympathetic over cholinergic signaling. Rapid onset of tumorigenesis induced a burst of Reg3y release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long lasting dysbiosis dominated by Gram positive Clostridium species. Pharmacological blockade of B-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin or co-housing of tumor bearers with tumor free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Cancer patients harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extra-intestinal malignancies requiring specific therapies.

Published
2021

25. Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage

Author

Fluckiger, Aurelie, Daillere, Romain, Sassi, Mohamed, Sixt, Barbara Susanne, Liu, Peng, Loos, Friedemann, Richard, Corentin, Rabu, Catherine, Alou, Maryam Tidjani, Goubet, Anne-Gaelle, Lemaitre, Fabien, Ferrere, Gladys, Derosa, Lisa, Duong, Connie P. M., Messaoudene, Meriem, Gagne, Andreanne, Joubert, Philippe, De Sordi, Luisa, Debarbieux, Laurent, Simon, Sylvain, Scarlata, Clara-Maria, Ayyoub, Maha, Palermo, Belinda, Facciolo, Francesco, Boidot, Romain, Wheeler, Richard, Boneca, Ivo Gomperts, Sztupinszki, Zsofia, Papp, Krisztian, Csabai, Istvan, Pasolli, Edoardo, Segata, Nicola, Lopez-Otin, Carlos, Szallasi, Zoltan, Andre, Fabrice, Iebba, Valerio, Quiniou, Valentin, Klatzmann, David, Boukhalil, Jacques, Khelaifia, Saber, Raoult, Didier, Albiges, Laurence, Escudier, Bernard, Eggermont, Alexander, Mami-Chouaib, Fathia, Nistico, Paola, Ghiringhelli, Francois, Routy, Bertrand, Labarriere, Nathalie, Cattoir, Vincent, Kroemer, Guido, Zitvogel, Laurence, Fluckiger, Aurelie, Daillere, Romain, Sassi, Mohamed, Sixt, Barbara Susanne, Liu, Peng, Loos, Friedemann, Richard, Corentin, Rabu, Catherine, Alou, Maryam Tidjani, Goubet, Anne-Gaelle, Lemaitre, Fabien, Ferrere, Gladys, Derosa, Lisa, Duong, Connie P. M., Messaoudene, Meriem, Gagne, Andreanne, Joubert, Philippe, De Sordi, Luisa, Debarbieux, Laurent, Simon, Sylvain, Scarlata, Clara-Maria, Ayyoub, Maha, Palermo, Belinda, Facciolo, Francesco, Boidot, Romain, Wheeler, Richard, Boneca, Ivo Gomperts, Sztupinszki, Zsofia, Papp, Krisztian, Csabai, Istvan, Pasolli, Edoardo, Segata, Nicola, Lopez-Otin, Carlos, Szallasi, Zoltan, Andre, Fabrice, Iebba, Valerio, Quiniou, Valentin, Klatzmann, David, Boukhalil, Jacques, Khelaifia, Saber, Raoult, Didier, Albiges, Laurence, Escudier, Bernard, Eggermont, Alexander, Mami-Chouaib, Fathia, Nistico, Paola, Ghiringhelli, Francois, Routy, Bertrand, Labarriere, Nathalie, Cattoir, Vincent, Kroemer, Guido, and Zitvogel, Laurence

Abstract

Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Enterococcus hirae. Mice bearing E. hirae harboring this prophage mounted a TMP-specific H-2K(b)-restricted CD8(+) T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice. In renal and lung cancer patients, the presence of the enterococcal prophage in stools and expression of a TMP-cross-reactive antigen by tumors correlated with long-term benefit of PD-1 blockade therapy. In melanoma patients, T cell clones recognizing naturally processed cancer antigens that are cross-reactive with microbial peptides were detected.

Published
2020
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26. Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

Author

Ferrere, Gladys, primary, Tidjani Alou, Maryam, additional, Liu, Peng, additional, Goubet, Anne-Gaëlle, additional, Fidelle, Marine, additional, Kepp, Oliver, additional, Durand, Sylvère, additional, Iebba, Valerio, additional, Fluckiger, Aurélie, additional, Daillère, Romain, additional, Thelemaque, Cassandra, additional, Grajeda-Iglesias, Claudia, additional, Alves Costa Silva, Carolina, additional, Aprahamian, Fanny, additional, Lefevre, Déborah, additional, Zhao, Liwei, additional, Ryffel, Bernhard, additional, Colomba, Emeline, additional, Arnedos, Monica, additional, Drubay, Damien, additional, Rauber, Conrad, additional, Raoult, Didier, additional, Asnicar, Francesco, additional, Spector, Tim, additional, Segata, Nicola, additional, Derosa, Lisa, additional, Kroemer, Guido, additional, and Zitvogel, Laurence, additional

Published
2021
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28. Profiling of oral microbiota and cytokines in COVID-19 patients

Author

Iebba, Valerio, primary, Zanotta, Nunzia, additional, Campisciano, Giuseppina, additional, Zerbato, Verena, additional, Di Bella, Stefano, additional, Cason, Carolina, additional, Morassut, Sara, additional, Luzzati, Roberto, additional, Confalonieri, Marco, additional, Palamara, Anna Teresa, additional, and Comar, Manola, additional

Published
2020
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29. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

Author

Wargo, Jennifer, primary, Andrews, Miles, additional, Duong, Connie, additional, Gopalakrishnan, Vancheswaran, additional, Iebba, Valerio, additional, Chen, Wei-Shen, additional, Derosa, Lisa, additional, Routy, Bertrand, additional, Ferrere, Gladys, additional, Fluckiger, Aurélie, additional, Roberti, Maria, additional, Opolon, Paule, additional, Roh, Whijae, additional, Spencer, Christine, additional, Curbelo, Irina Fernandez, additional, Vence, Luis, additional, Reuben, Alexandre, additional, Cooper, Zachary, additional, Prieto, Peter, additional, Khan, M. A. Wadud, additional, Lazar, Alexander, additional, Tetzlaff, Michael, additional, Hudgens, Courtney, additional, Gaudreau, Pierre-Olivier, additional, Nezi, Luigi, additional, Raoult, Didier, additional, Haydu, Lauren, additional, Tawbi, Hussein, additional, Hwu, Patrick, additional, Hwu, Wen-Jen, additional, Amaria, Rodabe, additional, Burton, Elizabeth, additional, Woodman, Scott, additional, Diab, Adi, additional, Patel, Sapna, additional, Glitza, Isabella, additional, Zhang, Jianhua, additional, Ajami, Nadim, additional, Petrosino, Joseph, additional, Jenq, Robert, additional, Davies, Michael, additional, Gershenwald, Jeffrey, additional, Sharma, Padmanee, additional, Allison, James, additional, Futreal, Andrew, additional, Zitvogel, Laurence, additional, ALOU, Maryam TIDJANI, additional, Yonekura, Satoru, additional, Cogdill, Alexandria, additional, Arora, Reetakshi, additional, Little, Latasha, additional, Gumbs, Curtis, additional, Wani, Khalida, additional, Callahan, Margaret, additional, Adamow, Mathew, additional, Postow, Michael, additional, Ariyan, Charlotte, additional, Gardner, Julie, additional, McQuade, Jennifer, additional, Wong, Michael, additional, and Zhao, Li, additional

Published
2020
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30. Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients

Author

Picard, Marion, primary, Yonekura, Satoru, additional, Slowicka, Karolina, additional, Petta, Ioanna, additional, Rauber, Conrad, additional, Routy, Bertrand, additional, Richard, Corentin, additional, Iebba, Valerio, additional, Tidjani Alou, Maryam, additional, Becharef, Sonia, additional, Ly, Pierre, additional, Pizzato, Eugenie, additional, Lehmann, Christian H. K., additional, Amon, Lukas, additional, Klein, Christophe, additional, Opolon, Paule, additional, Gomperts Boneca, Ivo, additional, Scoazec, Jean-Yves, additional, Hollebecque, Antoine, additional, Malka, David, additional, Ghiringhelli, François, additional, Dudziak, Diana, additional, Berx, Geert, additional, Vereecke, Lars, additional, van Loo, Geert, additional, Kroemer, Guido, additional, Zitvogel, Laurence, additional, and Roberti, Maria Paula, additional

Published
2020
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31. Cross-reactivity between tumor MHC class I–restricted antigens and an enterococcal bacteriophage

Author

Fluckiger, Aurélie, primary, Daillère, Romain, additional, Sassi, Mohamed, additional, Sixt, Barbara Susanne, additional, Liu, Peng, additional, Loos, Friedemann, additional, Richard, Corentin, additional, Rabu, Catherine, additional, Alou, Maryam Tidjani, additional, Goubet, Anne-Gaëlle, additional, Lemaitre, Fabien, additional, Ferrere, Gladys, additional, Derosa, Lisa, additional, Duong, Connie P. M., additional, Messaoudene, Meriem, additional, Gagné, Andréanne, additional, Joubert, Philippe, additional, De Sordi, Luisa, additional, Debarbieux, Laurent, additional, Simon, Sylvain, additional, Scarlata, Clara-Maria, additional, Ayyoub, Maha, additional, Palermo, Belinda, additional, Facciolo, Francesco, additional, Boidot, Romain, additional, Wheeler, Richard, additional, Boneca, Ivo Gomperts, additional, Sztupinszki, Zsofia, additional, Papp, Krisztian, additional, Csabai, Istvan, additional, Pasolli, Edoardo, additional, Segata, Nicola, additional, Lopez-Otin, Carlos, additional, Szallasi, Zoltan, additional, Andre, Fabrice, additional, Iebba, Valerio, additional, Quiniou, Valentin, additional, Klatzmann, David, additional, Boukhalil, Jacques, additional, Khelaifia, Saber, additional, Raoult, Didier, additional, Albiges, Laurence, additional, Escudier, Bernard, additional, Eggermont, Alexander, additional, Mami-Chouaib, Fathia, additional, Nistico, Paola, additional, Ghiringhelli, François, additional, Routy, Bertrand, additional, Labarrière, Nathalie, additional, Cattoir, Vincent, additional, Kroemer, Guido, additional, and Zitvogel, Laurence, additional

Published
2020
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32. Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients

Author

Derosa, Lisa, primary, Routy, Bertrand, additional, Fidelle, Marine, additional, Iebba, Valerio, additional, Alla, Laurie, additional, Pasolli, Edoardo, additional, Segata, Nicola, additional, Desnoyer, Aude, additional, Pietrantonio, Filippo, additional, Ferrere, Gladys, additional, Fahrner, Jean-Eudes, additional, Le Chatellier, Emmanuelle, additional, Pons, Nicolas, additional, Galleron, Nathalie, additional, Roume, Hugo, additional, Duong, Connie P.M., additional, Mondragón, Laura, additional, Iribarren, Kristina, additional, Bonvalet, Mélodie, additional, Terrisse, Safae, additional, Rauber, Conrad, additional, Goubet, Anne-Gaëlle, additional, Daillère, Romain, additional, Lemaitre, Fabien, additional, Reni, Anna, additional, Casu, Beatrice, additional, Alou, Maryam Tidjani, additional, Alves Costa Silva, Carolina, additional, Raoult, Didier, additional, Fizazi, Karim, additional, Escudier, Bernard, additional, Kroemer, Guido, additional, Albiges, Laurence, additional, and Zitvogel, Laurence, additional

Published
2020
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33. Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility

Author

Riganelli, Lucia, primary, Iebba, Valerio, additional, Piccioni, Mariagrazia, additional, Illuminati, Isabella, additional, Bonfiglio, Giulia, additional, Neroni, Bruna, additional, Calvo, Ludovica, additional, Gagliardi, Antonella, additional, Levrero, Massimo, additional, Merlino, Lucia, additional, Mariani, Marianna, additional, Capri, Oriana, additional, Pietrangeli, Daniela, additional, Schippa, Serena, additional, and Guerrieri, Francesca, additional

Published
2020
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34. Physiologic colonic uptake of 18F-FDG on PET/CT predicts immunotherapy response and gut microbiome diversity in patients with advanced non-small cell lung cancer (NSCLC).

Author

Cvetkovic, Lena, primary, Régis, Claudine, additional, Iebba, Valerio, additional, Derosa, Lisa, additional, Leblond, Antoine, additional, Malo, Julie, additional, Messaoudene, Meriem, additional, Belkaid, Wiam, additional, Elkrief, Arielle, additional, Routy, Bertrand, additional, and Juneau, Daniel, additional

Published
2020
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35. Combining amplicon sequencing and metabolomics in cirrhotic patients

Author

Iebba, Valerio, Guerrieri, Francesca, Di Gregorio, Vincenza, Levrero, Massimo, Gagliardi, Antonella, Santangelo, Floriana, Sobolev, Anatoly P., Circi, Simone, Giannelli, Valerio, Mannina, Luisa, Schippa, Serena, and Merli, Manuela

Subjects
16S sequencing, liver cirrhosis, microbiota, metabolomics
Abstract

In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood proinflammatory cytokines, while Ruminococcaceae and SCFAs played a protective role. Within the peripheral blood and faeces, certain species (Stenotrophomonas pavanii, Methylobacterium extorquens) and metabolites (methanol, threonine) were positively related to HE. Cirrhotic patients thus harbour a 'functional dysbiosis' in the faeces and peripheral/portal blood, with specific keystone species and metabolites related to clinical markers of systemic inflammation and HE.

Published
2018

36. Nasal microbiota in RSV microbiota

Author

Persia, Sabrina, primary, Frassanito, Antonella, additional, Nenna, Raffaella, additional, Petrarca, Laura, additional, Di Mattia, Greta, additional, Merola, Antonella, additional, Iebba, Valerio, additional, Schippa, Serena, additional, Scagnolari, Carolina, additional, Pierangeli, Alessandra, additional, and Midulla, Fabio, additional

Published
2019
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37. Intestinal Akkermansia muciniphilapredicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila(Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n= 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium halliiand Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.

Published
2022
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38. A distinctive 'microbial signature' in celiac pediatric patients

Author

Longhi Catia, Checchi Monica, Totino Valentina, Di Nardo Giovanni, Barbato Maria, Iebba Valerio, Schippa Serena, Maiella Giulia, Cucchiara Salvatore, and Conte Maria

Subjects
Microbiology, QR1-502
Abstract

Abstract Background Celiac Disease (CD) is an autoimmune disorder of the small intestine in which dietary gluten ingestion leads to a chronic enteropathy. Recently, scientific evidence suggested a potential role of gut microbiota in CD. To have a snapshot of dominant duodenal microbiota we analyzed the mucosa-associated microbiota of 20 children with CD, before and after a gluten-free diet (GFD) regimen, and of 10 controls. Total DNA was extracted from duodenal biopsies and amplification products of 16S ribosomal DNA were compared by temporal temperature gradient gel electrophoresis (TTGE). TTGE profiles were analyzed by statistical multivariate analysis. Results The average number of bands in TTGE profiles was significantly higher (P < 0.0001) in active (n.b. 16.7 ± 0.7) and inactive states (n.b. 13.2 ± 0.8) than in controls (n.b. 3.7 ± 1.3). Mean interindividual similarity index was 54.9% ± 14.9% for active disease, 55.6% ± 15.7% for remission state and 21.8% ± 30.16% for controls. Similarity index between celiac children before and after GFD treatment was 63.9% ± 15.8%. Differences in microbiota biodiversity were among active and remission state (P = 0.000224) and amid active CD and controls (P < 0.001). Bacteroides vulgatus and Escherichia coli were detected more often in CD patients than in controls (P < 0.0001). Conclusions Overall, the results highlighted a peculiar microbial TTGE profile and a significant higher biodiversity in CD pediatric patients' duodenal mucosa. The possible pathophysiological role of these microbial differences needs further characterization.

Published
2010
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40. Postbiotic Protective Activity of Lactobacillus Rhamnosus GG-Derived Factors on Pathogen Lipopolysaccharide (LPS)-Induced Damage of Human Colonic Smooth Muscle

Author

Cicenia, Alessia, Santangelo, Floriana, Gambardella, Lucia, Iebba, Valerio, Scirocco, Annunziata, Marignani, Michela, Chirletti, Piero, Pallotta, Lucia, Carabotti, Marilia, Corazziari, Enrico Stefano, Schippa, Serena, Severi, Carola, Cicenia, Alessia, Santangelo, Floriana, Gambardella, Lucia, Iebba, Valerio, Scirocco, Annunziata, Marignani, Michela, Chirletti, Piero, Pallotta, Lucia, Carabotti, Marilia, Corazziari, Enrico Stefano, Schippa, Serena, and Severi, Carola

Published
2015

41. Rebuilding the Gut Microbiota Ecosystem

Author

Gagliardi, Antonella, primary, Totino, Valentina, additional, Cacciotti, Fatima, additional, Iebba, Valerio, additional, Neroni, Bruna, additional, Bonfiglio, Giulia, additional, Trancassini, Maria, additional, Passariello, Claudio, additional, Pantanella, Fabrizio, additional, and Schippa, Serena, additional

Published
2018
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43. 1014 - Microbiota Composition, Metabolic Profiles and Inflammatory Host Response after Fecal Microbiota Transplantation (FMT) for Recurrent Clostridium Difficile Infection. Does Proteobacteria Abundance Predict the Response to FMT?

Author

Schippa, Serena, primary, Bruno, Giovanni, additional, Cicerone, Clelia, additional, Badiali, Danilo, additional, Auria, Stefania, additional, Zaccari, Piera, additional, Casadio, Marco, additional, Trancassini, Maria, additional, Gagliardi, Antonella, additional, Neroni, Bruna, additional, Bonfiglio, Giulia, additional, Oliva, Alessandra, additional, D'abramo, Alessandra, additional, Iebba, Valerio, additional, Macone, Alberto, additional, Vullo, Vincenzo, additional, and Corazziari, Enrico, additional

Published
2018
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46. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Allelic Variants Relate to Shifts in Faecal Microbiota of Cystic Fibrosis Patients

Author

Schippa, Serena, Iebba, Valerio, Santangelo, Floriana, Antonella, Gagliardi, DE BIASE, Riccardo Valerio, Antonella, Stamato, Serenella, Bertasi, Lucarelli, Marco, Conte, Maria Pia, Quattrucci, Serena, Neeraj, Vij, Schippa, Serena, Iebba, Valerio, Santangelo, Floriana, Antonella, Gagliardi, DE BIASE, Riccardo Valerio, Antonella, Stamato, Serenella, Bertasi, Lucarelli, Marco, Conte, Maria Pia, Quattrucci, Serena, and Neeraj, Vij

Subjects
Male, Cystic Fibrosis, Genotyping Techniques, Applied Microbiology, Cystic Fibrosis Transmembrane Conductance Regulator, micorbiota, Severity of Illness Index, Cystic fibrosis, Feces, fluids and secretions, Autosomal Recessive, RNA, Ribosomal, 16S, Respiratory system, Child, Electrophoresis, Agar Gel, Escherichia Coli, Gastrointestinal tract, Multidisciplinary, Ecology, biology, Discriminant Analysis, cftr, Middle Aged, Cystic fibrosis transmembrane conductance regulator, Bacterial Pathogens, Phenotype, medicine.anatomical_structure, Medical Microbiology, Child, Preschool, Medicine, Female, Pediatric Gastroenterology, Research Article, Adult, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Science, Ileum, Gastroenterology and Hepatology, Microbiology, Microbial Ecology, Young Adult, Species Specificity, Meconium, Genetic Mutation, Genetics, medicine, Humans, Least-Squares Analysis, Allele, Biology, cystic fibrosi, Alleles, Demography, Clinical Genetics, Human Genetics, medicine.disease, Mucus, cystic fibrosis, Mutation, Genetics of Disease, Immunology, biology.protein, Metagenome
Abstract

IntroductionIn this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age.MethodsThirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure.ResultsPatients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme) were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum) were reduced.ConclusionsThis is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

Published
2013

47. Characterization of mucosa-associated and fecal microbiota of children with autism spectre disorder

Author

IEBBA, VALERIO, SCHIPPA, Serena, VALITUTTI, FRANCESCO, SANTANGELO, FLORIANA, S. Gatti, I. Celletti, S. Leoni, TROVATO, CHIARA MARIA, IORFIDA, DONATELLA, P. Di Matteo, Marazzato, Massimiliano, CONTE, Maria Pia, BARBATO, Maria, Iebba, Valerio, Schippa, Serena, Valitutti, Francesco, Santangelo, Floriana, S., Gatti, I., Celletti, S., Leoni, Trovato, CHIARA MARIA, Iorfida, Donatella, P., Di Matteo, Marazzato, Massimiliano, Conte, Maria Pia, and Barbato, Maria

Published
2013

48. Strategie terapeutiche innovative basate sulla duplice attività, antibatterica e probiotica, del predatore batterico Bdellovibrio bacteriovorus

Author

Iebba, Valerio, Totino, Valentina, Ciotoli, L., Santangelo, Floriana, AMBROSI SACCONI ROSATI, Cecilia, Pompili, M., Passariello, C., Cellini, A., Pantanella, Fabrizio, Selan, L., Artini, M., Trancassini, Maria, Nicoletti, M., Quattrucci, Serena, Nencioni, Lucia, Schippa, S., Iebba, Valerio, Totino, Valentina, L., Ciotoli, Santangelo, Floriana, AMBROSI SACCONI ROSATI, Cecilia, M., Pompili, C., Passariello, A., Cellini, Pantanella, Fabrizio, L., Selan, M., Artini, Trancassini, Maria, M., Nicoletti, Quattrucci, Serena, Nencioni, Lucia, and S., Schippa

Subjects
Bdellovibrio, antibatterico, fibrosi cistica
Abstract

Introduzione: Bdellovibrio bacteriovorus preda batteri Gram-negativi ed è ubiquitario in vari ambienti, dove svolge un ruolo di equilibratore delle specie batteriche presenti. Molte sono le infezioni causate da biofilm microbici misti, di solito resistenti alle cure antibiotiche: ne è un esempio la Fibrosi Cistica (FC). Il primo obiettivo del presente studio è stato valutare l’attività antibatterica di B. bacteriovorus verso specie batteriche isolate da pazienti FC. Il secondo obiettivo è stato valutare l’utilizzo di B. bacteriovorus come probiotico, valutandone la presenza nell’ecosistema polimicrobico intestinale umano, in soggetti sani e affetti da Celiachia, Morbo di Crohn, Colite Ulcerosa, e FC. Metodi: L’attività contro biofilm preformati di Pseudomonas aeruginosa e Staphylococcus aureus è stata misurata sia in sistemi statici (piastre) che dinamici (bioflux). Con lo zymogramma è stata inoltre valutata l’attività litica contro tali ceppi. Al fine di valutare la presenza del B. bacteriovorus nell’ecosistema intestinale umano, il DNA totale di campioni fecali e bioptici collezionati da pazienti sani e malati è stato utilizzato per effettuare Real-time PCR con primers B. bacteriovorus-specifici. Risultati: I risultati ottenuti indicano una predazione di B. bacteriovorus non solo nei confronti del Gram-negativo P. aeruginosa, ma anche, e per la prima volta osservata, del Gram-positivo S. aureus. Le prove in statico hanno evidenziato una significativa diminuzione del 70% del biofilm dopo 24 ore di incubazione, mentre le prove in dinamico una diminuzione del 35% dopo 15 ore di incubazione. Inoltre, per la prima volta, abbiamo dimostrato la presenza di B. bacteriovorus a livello della mucosa intestinale e la sua significativa diminuzione nei soggetti malati, rispetto ai controlli. Conclusioni: I risultati ottenuti incoraggiano una più approfondita ricerca sul Bdellovibrio, per un suo eventuale utilizzo in strategie terapeutiche innovative volte sia a combattere infezioni sostenute da biofilm batterici (antibatterico), che al ripristino di ecosistemi microbici come quello intestinale (probiotico)

Published
2013

49. Influence of oral conditions on colonization by highly toxigenic Staphylococcus aureus strains

Author

Claudio, Passariello, Puttini, M., Iebba, Valerio, Pera, P., Gigola, P., Passariello, Claudio, Puttini, M., Iebba, Valerio, Pera, P., and Gigola, P.

Subjects
Adult, Male, Methicillin-Resistant Staphylococcus aureus, Staphylococcus aureus, nasal carriage, Genotype, Virulence Factors, Bacterial Toxins, Alveolar Bone Loss, Gingiva, Exotoxins, staphylococcus aureu, Nose, Bacterial Physiological Phenomena, periodontitis, fixed prosthesis, oral carriage, staphylococcus aureus, Dental Prosthesis, Young Adult, periodontiti, Humans, Periodontal Pocket, Periodontitis, Mouth, Dental Plaque Index, Mouth Mucosa, Genetic Variation, Middle Aged, Bacterial Load, Cheek, Phenotype, Chronic Periodontitis, fixed prosthesi, Female, Periodontal Index
Abstract

Objectives: As the oral cavity is regarded as a relevant site for Staphylococcus aureus colonization and interhuman transmission, this study aimed to investigate whether different oral conditions influence the rates of S. aureus oral carriage and genetic characters of S. aureus isolates. Subjects and methods: Staphylococcus aureus was searched in samples collected from cheek, gingival margin, and anterior nares of 45 healthy subjects, 27 periodontitis affected subjects, and 29 subjects with fixed prosthetic restorations. Isolates were screened for 17 genetic determinants, and Partial Least Square Discriminant Analysis was performed to evaluate whether specific characters correlated with oral condition or site of isolation. Results: The three subject groups showed comparable nasal carriage rates but, both the periodontitis and prosthetic restoration groups showed significantly higher oral carriage rates, as compared to healthy subjects (P=0.01 and 0.02, respectively). Moreover, periodontitis affected subjects hosted strains possessing a distinct genotypic and phenotypic background, characterized by the presence of a larger number of exotoxins encoding genes. Conclusions: These data confirm that the oral cavity is an important site of S. aureus colonization and demonstrate that conditions modifying the oral environment, as the presence of periodontitis and of fixed prosthetic restorations, promote S. aureus carriage and may favor the spread of more pathogenic strains. © 2011 John Wiley & Sons A/S.

Published
2012

50. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in fecal microbiota of cystic fibrosis patients

Author

Iebba, Valerio, Schippa, Serena, Santangelo, Floriana, DE BIASE, Riccardo Valerio, Stamato, Antonella, Bertasi, S., Rolla, M., Lucarelli, Marco, Conte, Maria Pia, Quattrucci, Serena, Iebba, Valerio, Schippa, Serena, Santangelo, Floriana, DE BIASE, Riccardo Valerio, Stamato, Antonella, S., Bertasi, M., Rolla, Lucarelli, Marco, Conte, Maria Pia, and Quattrucci, Serena

Published
2012

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