Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cancer Discovery Année : 2022

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

Kousuke Ueda
Gibrail Mansouri
  • Fonction : Auteur
Angélique Puget
  • Fonction : Auteur
Fanny Mann
  • Fonction : Auteur
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  • IdHAL : fanny-mann
Michel Neunlist
Anne Bessard
  • Fonction : Auteur
Jacques Bosq
Paul Hofman
Connie P.M. Duong
Sophie Ugolini
Valentin Quiniou
Sylvie Berrard
Bernhard Ryffel
  • Fonction : Auteur
Oliver Kepp
Bertrand Routy
Leonardo Lordello
  • Fonction : Auteur
Mohamed-Amine Bani
Nicola Segata
Fjodor Yousef Yengej
  • Fonction : Auteur
Hans Clevers
Edoardo Pasolli

Résumé

Abstract Gut dysbiosis has been associated with intestinal and extraintestinal 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. The rapid onset of tumorigenesis induced a burst of REG3γ release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long-lasting dysbiosis dominated by Gram-positive Clostridium species. Pharmacologic blockade of β-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin, or cohousing of tumor bearers with tumor-free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Patients with cancer harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extraintestinal malignancies requiring specific therapies. Significance: Whether gut dysbiosis promotes tumorigenesis and how it controls tumor progression remain open questions. We show that 50% of transplantable extraintestinal malignancies triggered a β-adrenergic receptor–dependent ileal mucosa atrophy, associated with increased gut permeability, sustained Clostridium spp.–related dysbiosis, and cancer growth. Vancomycin or propranolol prevented cancer-associated stress ileopathy. This article is highlighted in the In This Issue feature, p. 873

Dates et versions

hal-03642500 , version 1 (15-04-2022)

Identifiants

Citer

Satoru Yonekura, Safae Terrisse, Carolina Alves Costa Silva, Antoine Lafarge, Valerio Iebba, et al.. Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis. Cancer Discovery, 2022, 12 (4), pp.1128-1151. ⟨10.1158/2159-8290.CD-21-0999⟩. ⟨hal-03642500⟩
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