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

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

doi:10.1158/2159-8290.CD-21-0999

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

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

44 Citations (Scopus)

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.

Original language	English
Journal	Cancer Discovery
Early online date	20 Dec 2021
DOIs	https://doi.org/10.1158/2159-8290.CD-21-0999
Publication status	Published - Apr 2022

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Yonekura, S., Terrisse, S., Alves Costa Silva, C., Lafarge, A., Iebba, V., Ferrere, G., Goubet, A.-G., Fahrner, J.-E., Lahmar, I., Ueda, K., Mansouri, G., Pizzato, E., Ly, P., Mazzenga, M., Thelemaque, C., Fidelle, M., Jaulin, F., Cartry, J., Deloger, M., ... Zitvogel, L. (2022). Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-21-0999

@article{8b5b7fe719e04c698fcd6be64cf2672f,

title = "Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis",

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.",

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

note = "Copyright {\textcopyright}2021, American Association for Cancer Research.",

year = "2022",

month = apr,

doi = "10.1158/2159-8290.CD-21-0999",

language = "English",

journal = "Cancer Discovery",

issn = "2159-8274",

publisher = "American Association for Cancer Research Inc.",

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Yonekura, S, Terrisse, S, Alves Costa Silva, C, Lafarge, A, Iebba, V, Ferrere, G, Goubet, A-G, Fahrner, J-E, Lahmar, I, Ueda, K, Mansouri, G, Pizzato, E, Ly, P, Mazzenga, M, Thelemaque, C, Fidelle, M, Jaulin, F, Cartry, J, Deloger, M, Aglave, M, Droin, N, Opolon, P, Puget, A, Mann, F, Neunlist, M, Bessard, A, Aymeric, L, Matysiak-Budnik, T, Bosq, J, Hofman, P, Duong, CPM, Ugolini, S, Quiniou, V, Berrard, S, Ryffel, B, Kepp, O, Kroemer, G, Routy, B, Lordello, L, Bani, M-A, Segata, N, Yousef Yengej, F, Clevers, H, Scoazec, J-Y, Pasolli, E, Derosa, L & Zitvogel, L 2022, 'Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis', Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-21-0999

TY - JOUR

T1 - Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis

AU - Yonekura, Satoru

AU - Terrisse, Safae

AU - Alves Costa Silva, Carolina

AU - Lafarge, Antoine

AU - Iebba, Valerio

AU - Ferrere, Gladys

AU - Goubet, Anne-Gaelle

AU - Fahrner, Jean-Eudes

AU - Lahmar, Imran

AU - Ueda, Kosuke

AU - Mansouri, Gibrail

AU - Pizzato, Eugenie

AU - Ly, Pierre

AU - Mazzenga, Marine

AU - Thelemaque, Cassandra

AU - Fidelle, Marine

AU - Jaulin, Fanny

AU - Cartry, Jerome

AU - Deloger, Marc

AU - Aglave, Marine

AU - Droin, Nathalie

AU - Opolon, Paule

AU - Puget, Angelique

AU - Mann, Fanny

AU - Neunlist, Michel

AU - Bessard, Anne

AU - Aymeric, Laetitia

AU - Matysiak-Budnik, Tamara

AU - Bosq, Jacques

AU - Hofman, Paul

AU - Duong, Connie P M

AU - Ugolini, Sophie

AU - Quiniou, Valentin

AU - Berrard, Sylvie

AU - Ryffel, Bernhard

AU - Kepp, Oliver

AU - Kroemer, Guido

AU - Routy, Bertrand

AU - Lordello, Leonardo

AU - Bani, Mohamed-Amine

AU - Segata, Nicola

AU - Yousef Yengej, Fjodor

AU - Clevers, Hans

AU - Scoazec, Jean-Yves

AU - Pasolli, Edoardo

AU - Derosa, Lisa

AU - Zitvogel, Laurence

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

U2 - 10.1158/2159-8290.CD-21-0999

DO - 10.1158/2159-8290.CD-21-0999

M3 - Article

C2 - 34930787

SN - 2159-8274

JO - Cancer Discovery

JF - Cancer Discovery

ER -

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

Abstract

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