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

Gut dysbiosis has been associated with intestinal and extra-intestinal malignancies butwhether and how carcinogenesis drives compositional shifts of the microbiome to its ownbenefit remains an open conundrum. Here we show that malignant processes can cause ilealmucosa atrophy, with villous microvascular constriction associated with dominance ofsympathetic over cholinergic signaling. Rapid onset of tumorigenesis induced a burst ofReg3gamma release by ileal cells, and transient epithelial barrier permeability that culminated inovert and long lasting dysbiosis dominated by Gram positive Clostridium species.Pharmacological blockade of beta-adrenergic receptors or genetic deficiency in Adrb2 gene,vancomycin or co-housing of tumor bearers with tumor free littermates prevented cancerinducedileopathy, eventually slowing tumor growth kinetics. Cancer patients harbor distincthallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy isa corollary disease of extra-intestinal malignancies requiring specific therapies.