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 / Zagato, E., Pozzi, C., Bertocchi, A., Schioppa, T., Saccheri, F., Guglietta, S., Fosso, B., Melocchi, L., Nizzoli, G., Troisi, J., Marzano, M., Oresta, B., Spadoni, I., Atarashi, K., Carloni, S., Arioli, S., Fornasa, G., Asnicar, F., Segata, N., Guglielmetti, S., et al.. - In: NATURE MICROBIOLOGY. - ISSN 2058-5276. - 5:3(2020), pp. 511-524. [10.1038/s41564-019-0649-5]
Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth
Asnicar, Francesco;Segata, Nicola;
2020-01-01
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.| File | Dimensione | Formato | |
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