Early-life microbiota exposure restricts myeloid-derived suppressor cell-driven colonic tumorigenesis Running Title: Early-life microbiota restricts colonic tumorigenesis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Immunology Research Année : 2019

Early-life microbiota exposure restricts myeloid-derived suppressor cell-driven colonic tumorigenesis Running Title: Early-life microbiota restricts colonic tumorigenesis

Akihito Harusato
  • Fonction : Auteur
Emilie Viennois
Shingo Matsuyama
  • Fonction : Auteur
Hirohito Abo
  • Fonction : Auteur
Satoru Osuka
  • Fonction : Auteur
Nicholas W Lukacs
  • Fonction : Auteur
Yoshito Itoh
  • Fonction : Auteur
Didier Merlin
  • Fonction : Auteur
Andrew T Gewirtz
  • Fonction : Auteur
Timothy L Denning
  • Fonction : Auteur
  • PersonId : 1057061

Résumé

Gut microbiota and their metabolites are instrumental in regulating homeostasis at intestinal and extraintestinal sites. However, the complex effects of prenatal and early postnatal microbial exposure on adult health and disease outcomes remain incompletely understood. Here, we showed that mice raised under germ-free conditions until weaning and then transferred to specific pathogen-free (SPF) conditions harbored altered microbiota composition, augmented inflammatory cytokine and chemokine expression, and were hyper-susceptible to colitis-associated tumorigenesis later in adulthood. Increased number and size of colon tumors and intestinal epithelial cell proliferation in recolonized germ-free mice were associated with augmented intratumoral CXCL1, CXCL2, and CXCL5 expression and granulocytic myeloid-derived suppressor cell (G-MDSC) accumulation. Consistent with these findings, CXCR2 neutralization in recolonized germ-free mice completely reversed the exacerbated susceptibility to colitis- associated tumorigenesis. Collectively, our findings highlight a crucial role for early-life microbial exposure in establishing intestinal homeostasis that restrains colon cancer in adulthood.
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Dates et versions

hal-02335668 , version 1 (28-10-2019)

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Akihito Harusato, Emilie Viennois, Lucie Etienne-Mesmin, Shingo Matsuyama, Hirohito Abo, et al.. Early-life microbiota exposure restricts myeloid-derived suppressor cell-driven colonic tumorigenesis Running Title: Early-life microbiota restricts colonic tumorigenesis. Cancer Immunology Research, 2019, 7 (4), pp.544-551. ⟨10.1158/2326-6066.CIR-18-0444⟩. ⟨hal-02335668⟩
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