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.

Zagato, E., Pozzi, C., Bertocchi, A., Schioppa, T., Saccheri, F., Guglietta, S., et al. (2020). Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. NATURE MICROBIOLOGY, 5(3), 511-524 [10.1038/s41564-019-0649-5].

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

Nizzoli G.;Spadoni I.;Guglielmetti S.;
2020

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.
Articolo in rivista - Articolo scientifico
Microbiota, Faecalibaculum rodentium, Intestinal Tumour
English
2020
5
3
511
524
partially_open
Zagato, E., Pozzi, C., Bertocchi, A., Schioppa, T., Saccheri, F., Guglietta, S., et al. (2020). Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. NATURE MICROBIOLOGY, 5(3), 511-524 [10.1038/s41564-019-0649-5].
File in questo prodotto:
File Dimensione Formato  
Zagato-2020-Nature Microbiol-VoR.pdf

Solo gestori archivio

Descrizione: Article
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Tutti i diritti riservati
Dimensione 7.66 MB
Formato Adobe PDF
7.66 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Zagato-2020-Nature Microb-preprint.pdf

accesso aperto

Tipologia di allegato: Submitted Version (Pre-print)
Licenza: Altro
Dimensione 18.52 MB
Formato Adobe PDF
18.52 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/452092
Citazioni
  • Scopus 256
  • ???jsp.display-item.citation.isi??? 241
Social impact