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1. 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

2. 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

3. 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

4. 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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5. Gut microbiota related to Giardia duodenalis, Entamoeba spp. and Blastocystis hominis infections in humans from Cote d'Ivoire

Author

Iebba, Valerio, Santangelo, Floriana, Totino, Valentina, Pantanella, Fabrizio, Monsia, Anatole, Di Cristanziano, Veronica, Di Cave, David, Schippa, Serena, Berrilli, Federica, D'Alfonso, Rossella, Iebba, Valerio, Santangelo, Floriana, Totino, Valentina, Pantanella, Fabrizio, Monsia, Anatole, Di Cristanziano, Veronica, Di Cave, David, Schippa, Serena, Berrilli, Federica, and D'Alfonso, Rossella

Abstract

Introduction: Literature data provide little information about protozoa infections and gut microbiota compositional shifts in humans. This preliminary study aimed to describe the fecal bacterial community composition of people from Cote d'Ivoire harboring Giardia duodenalis, Entamoeba spp., and Blastocystis hominis, in trying to discover possible alterations in their fecal microbiota structure related to the presence of such parasites. Methodology: Twenty fecal samples were collected from people inhabiting three different localities of Cote d'Ivoire for copromicroscopic analysis and molecular identification of G. duodenalis, Entamoeba spp., and B. hominis. Temporal temperature gradient gel electrophoresis (TTGE) was used to obtain a fingerprint of the overall bacterial community; quantitative polymerase chain reaction (qPCR) was used to define the relative abundances of selected bacterial species/group, and multivariate statistical analyses were employed to correlate all data. Results: Cluster analysis revealed a significant separation of TTGE profiles into four clusters (p < 0.0001), with a marked difference for G. duodenalis-positive samples in relation to the others (p = 5.4x10(-6)). Interestingly, qPCR data showed how G. duodenalis-positive samples were related to a dysbiotic condition that favors potentially harmful species (such as Escherichia coli), while Entamoeba spp./B. hominis-positive subjects were linked to a eubiotic condition, as shown by a significantly higher Faecalibacterium prausnitzii-Escherichia coli ratio. Conclusions: This preliminary investigation demonstrates a differential fecal microbiota structure in subjects infected with G. duodenalis or Entamoeba spp./B. hominis, paving the way for using further next-generation DNA technologies to better understand host-parasite-bacteria interactions, aimed at identifying potential indicators of microbiota changes.

Published
2016

6. Gut microbiota related to Giardia duodenalis, Entamoeba spp. and Blastocystis hominis infections in humans from Cote d'Ivoire

Author

Iebba, Valerio, Santangelo, Floriana, Totino, Valentina, Pantanella, Fabrizio, Monsia, Anatole, Di Cristanziano, Veronica, Di Cave, David, Schippa, Serena, Berrilli, Federica, D'Alfonso, Rossella, Iebba, Valerio, Santangelo, Floriana, Totino, Valentina, Pantanella, Fabrizio, Monsia, Anatole, Di Cristanziano, Veronica, Di Cave, David, Schippa, Serena, Berrilli, Federica, and D'Alfonso, Rossella

Abstract

Introduction: Literature data provide little information about protozoa infections and gut microbiota compositional shifts in humans. This preliminary study aimed to describe the fecal bacterial community composition of people from Cote d'Ivoire harboring Giardia duodenalis, Entamoeba spp., and Blastocystis hominis, in trying to discover possible alterations in their fecal microbiota structure related to the presence of such parasites. Methodology: Twenty fecal samples were collected from people inhabiting three different localities of Cote d'Ivoire for copromicroscopic analysis and molecular identification of G. duodenalis, Entamoeba spp., and B. hominis. Temporal temperature gradient gel electrophoresis (TTGE) was used to obtain a fingerprint of the overall bacterial community; quantitative polymerase chain reaction (qPCR) was used to define the relative abundances of selected bacterial species/group, and multivariate statistical analyses were employed to correlate all data. Results: Cluster analysis revealed a significant separation of TTGE profiles into four clusters (p < 0.0001), with a marked difference for G. duodenalis-positive samples in relation to the others (p = 5.4x10(-6)). Interestingly, qPCR data showed how G. duodenalis-positive samples were related to a dysbiotic condition that favors potentially harmful species (such as Escherichia coli), while Entamoeba spp./B. hominis-positive subjects were linked to a eubiotic condition, as shown by a significantly higher Faecalibacterium prausnitzii-Escherichia coli ratio. Conclusions: This preliminary investigation demonstrates a differential fecal microbiota structure in subjects infected with G. duodenalis or Entamoeba spp./B. hominis, paving the way for using further next-generation DNA technologies to better understand host-parasite-bacteria interactions, aimed at identifying potential indicators of microbiota changes.

Published
2016

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