TY - JOUR
T1 - Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth
AU - Zagato, Elena
AU - Pozzi, Chiara
AU - Bertocchi, Alice
AU - Schioppa, Tiziana
AU - Saccheri, Fabiana
AU - Guglietta, Silvia
AU - Fosso, Bruno
AU - Melocchi, Laura
AU - Nizzoli, Giulia
AU - Troisi, Jacopo
AU - Marzano, Marinella
AU - Oresta, Bianca
AU - Spadoni, Ilaria
AU - Atarashi, Koji
AU - Carloni, Sara
AU - Arioli, Stefania
AU - Fornasa, Giulia
AU - Asnicar, Francesco
AU - Segata, Nicola
AU - Guglielmetti, Simone
AU - Honda, Kenya
AU - Pesole, Graziano
AU - Vermi, William
AU - Penna, Giuseppe
AU - Rescigno, Maria
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41564-019-0649-5
DO - 10.1038/s41564-019-0649-5
M3 - Article
C2 - 31988379
AN - SCOPUS:85078437762
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
ER -