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 tumourigen- esis. 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 azoxymeth- ane- 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 endog- enous 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
Bruno Fosso;Marinella Marzano;Graziano Pesole;
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 tumourigen- esis. 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 azoxymeth- ane- 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 endog- enous anti-tumourigenic bacterial strains with strong diagnostic, therapeutic and translational potential.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.