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

Elena Zagato; Chiara Pozzi; Alice Bertocchi; Tiziana Schioppa; Fabiana Saccheri; Silvia Guglietta; Bruno Fosso; Laura Melocchi; Giulia Nizzoli; Jacopo Troisi; Marinella Marzano; Bianca Oresta; Ilaria Spadoni; Koji Atarashi; Sara Carloni; Stefania Arioli; Giulia Fornasa; Francesco Asnicar; Nicola Segata; Simone Guglielmetti; Kenya Honda; Graziano Pesole; William Vermi; Giuseppe Penna; Maria Rescigno

doi:10.1038/s41564-019-0649-5

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

Elena Zagato, Chiara Pozzi, Alice Bertocchi, Tiziana Schioppa, Fabiana Saccheri, Silvia Guglietta, Bruno Fosso, Laura Melocchi, Giulia Nizzoli, Jacopo Troisi, Marinella Marzano, Bianca Oresta, Ilaria Spadoni, Koji Atarashi, Sara Carloni, Stefania Arioli, Giulia Fornasa, Francesco Asnicar, Nicola Segata, Simone GuglielmettiKenya Honda, Graziano Pesole, William Vermi, Giuseppe Penna, Maria Rescigno

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

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 Apc^Min/+ 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.

Original language	English
Pages (from-to)	511-524
Number of pages	14
Journal	Nature Microbiology
Volume	5
Issue number	3
DOIs	https://doi.org/10.1038/s41564-019-0649-5
Publication status	Published - 2020 Mar 1

ASJC Scopus subject areas

Microbiology
Immunology
Applied Microbiology and Biotechnology
Genetics
Microbiology (medical)
Cell Biology

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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., ... Rescigno, M. (2020). Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. Nature Microbiology, 5(3), 511-524. https://doi.org/10.1038/s41564-019-0649-5

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, Vol. 5, No. 3, 01.03.2020, p. 511-524.

Research output: Contribution to journal › Article › peer-review

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, Honda, K, Pesole, G, Vermi, W, Penna, G & Rescigno, M 2020, 'Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth', Nature Microbiology, vol. 5, no. 3, pp. 511-524. https://doi.org/10.1038/s41564-019-0649-5

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. In: Nature Microbiology. 2020 ; Vol. 5, No. 3. pp. 511-524.

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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.",

author = "Elena Zagato and Chiara Pozzi and Alice Bertocchi and Tiziana Schioppa and Fabiana Saccheri and Silvia Guglietta and Bruno Fosso and Laura Melocchi and Giulia Nizzoli and Jacopo Troisi and Marinella Marzano and Bianca Oresta and Ilaria Spadoni and Koji Atarashi and Sara Carloni and Stefania Arioli and Giulia Fornasa and Francesco Asnicar and Nicola Segata and Simone Guglielmetti and Kenya Honda and Graziano Pesole and William Vermi and Giuseppe Penna and Maria Rescigno",

note = "Funding Information: We thank M. Bugatti and S. Licini (supported by Fondazione Beretta, Brescia, Italy) for their technical support in the histological analyses; A. Thomas and E. Pasolli for performing the bioinformatics analyses; C. Faccani for technical support for the in vitro experiments; and E. Mileti, C. Burrello and M. R. Giuffr{\'e} for their technical support for the in vivo experiments. This work has been supported by grants from the Italian Association for Cancer Research (grant no. AIRC IG 17628) and the European Research council (grant no. 615735, HOMEOGUT ERC) to M.R. E.Z., I.S. and A.B. were/are recipients of a FIRC fellowship. T.S. is a recipient of a fellowship from Fondazione Veronesi. G.F. is a recipient of a grant from the Italian Ministry of Health (grant no. GR-2013-02359806).",

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AU - Pozzi, Chiara

AU - Bertocchi, Alice

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AU - Saccheri, Fabiana

AU - Guglietta, Silvia

AU - Fosso, Bruno

AU - Melocchi, Laura

AU - Nizzoli, Giulia

AU - Troisi, Jacopo

AU - Marzano, Marinella

AU - Oresta, Bianca

AU - Spadoni, Ilaria

AU - Atarashi, Koji

AU - Carloni, Sara

AU - Arioli, Stefania

AU - Fornasa, Giulia

AU - Asnicar, Francesco

AU - Segata, Nicola

AU - Guglielmetti, Simone

AU - Honda, Kenya

AU - Pesole, Graziano

AU - Vermi, William

AU - Penna, Giuseppe

AU - Rescigno, Maria

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