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, Elena; Pozzi, Chiara; Bertocchi, Alice; Schioppa, Tiziana; Saccheri, Fabiana; Guglietta, Silvia; Fosso, Bruno; Melocchi, Laura; Nizzoli, Giulia; Troisi, Jacopo; Marzano, Marinella; Oresta, Bianca; Spadoni, Ilaria; Atarashi, Koji; Carloni, Sara; Arioli, Stefania; Fornasa, Giulia; Asnicar, Francesco; Segata, Nicola; Guglielmetti, Simone; Honda, Kenya; Pesole, Graziano; Vermi, William; Penna, Giuseppe; Rescigno, Maria. - 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.
2020
3
Zagato, Elena; Pozzi, Chiara; Bertocchi, Alice; Schioppa, Tiziana; Saccheri, Fabiana; Guglietta, Silvia; Fosso, Bruno; Melocchi, Laura; Nizzoli, Giulia; Troisi, Jacopo; Marzano, Marinella; Oresta, Bianca; Spadoni, Ilaria; Atarashi, Koji; Carloni, Sara; Arioli, Stefania; Fornasa, Giulia; Asnicar, Francesco; Segata, Nicola; Guglielmetti, Simone; Honda, Kenya; Pesole, Graziano; Vermi, William; Penna, Giuseppe; Rescigno, Maria
Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth / Zagato, Elena; Pozzi, Chiara; Bertocchi, Alice; Schioppa, Tiziana; Saccheri, Fabiana; Guglietta, Silvia; Fosso, Bruno; Melocchi, Laura; Nizzoli, Giulia; Troisi, Jacopo; Marzano, Marinella; Oresta, Bianca; Spadoni, Ilaria; Atarashi, Koji; Carloni, Sara; Arioli, Stefania; Fornasa, Giulia; Asnicar, Francesco; Segata, Nicola; Guglielmetti, Simone; Honda, Kenya; Pesole, Graziano; Vermi, William; Penna, Giuseppe; Rescigno, Maria. - In: NATURE MICROBIOLOGY. - ISSN 2058-5276. - 5:3(2020), pp. 511-524. [10.1038/s41564-019-0649-5]
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