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.

Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth / E. Zagato, C. Pozzi, A. Bertocchi, T. Schioppa, F. Saccheri, S. Guglietta, B. Fosso, L. Melocchi, G. Nizzoli, J. Troisi, M. Marzano, B. Oresta, I. Spadoni, K. Atarashi, S. Carloni, S. Arioli, G. Fornasa, F. Asnicar, N. Segata, S. Guglielmetti, K. Honda, G. Pesole, W. Vermi, G. Penna, M. Rescigno. - In: NATURE MICROBIOLOGY. - ISSN 2058-5276. - 5:3(2020 Mar), pp. 511-524. [10.1038/s41564-019-0649-5]

Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth

Zagato E.;Bertocchi A.;Saccheri F.;Melocchi L.;Nizzoli G.;Oresta B.;Spadoni I.;Carloni S.;Arioli S.;Guglielmetti S.;Pesole G.;Penna G.;Rescigno M.
2020-03

Abstract

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.
Settore MED/04 - Patologia Generale
Settore BIO/19 - Microbiologia Generale
Settore AGR/16 - Microbiologia Agraria
gen-2020
NATURE MICROBIOLOGY
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/742555
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