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The microbiota has been shown to promote intestinal tumourigenesis, but a possible anti-tumourigenic effect has also been postulated. Here, we demonstrate that changes in the microbiota and mucus composition are concomitant with tumourigenesis. We identified two anti-tumourigenic strains of the microbiota—Faecalibaculum rodentium and its human homologue, Holdemanella biformis—that are strongly under-represented during tumourigenesis. Reconstitution of ApcMin/+ or azoxymethane- and dextran sulfate sodium-treated mice with an isolate of F. rodentium (F. PB1) or its metabolic products reduced tumour growth. Both F. PB1 and H. biformis produced short-chain fatty acids that contributed to control protein acetylation and tumour cell proliferation by inhibiting calcineurin and NFATc3 activation in mouse and human settings. We have thus identified endogenous anti-tumourigenic bacterial strains with strong diagnostic, therapeutic and translational potential.
Elena Zagato,Chiara Pozzi,Alice Bertocchi,Tiziana Schioppa,Fabiana Saccheri,Silvia Guglietta,Bruno Fosso,Laura Melocchi,Giulia Nizzoli,Jacopo Troisi,Marinella Marzano,Bianca Oresta,Ilaria Spadoni,Koji Atarashi,Sara Carloni,Stefania Arioli,Giulia Fornasa,Francesco Asnicar,Nicola Segata,Simone Guglielmetti,Kenya Honda,Graziano Pesole,William Vermi,Giuseppe Penna,Maria Rescigno