Fecal DNA Virome Is Associated with the Development of Colorectal Neoplasia in a Murine Model of Colorectal Cancer
Yingshi Li,
Fan Zhang,
Huimin Zheng,
Sanjna Kalasabail,
Chloe Hicks,
Ka Yee Fung,
Adele Preaudet,
Tracy Putoczki,
Julia Beretov,
Ewan K. A. Millar,
Emad El-Omar,
Xiao-Tao Jiang,
Howard Chi Ho Yim
Affiliations
Yingshi Li
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Fan Zhang
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Huimin Zheng
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Sanjna Kalasabail
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Chloe Hicks
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Ka Yee Fung
Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria, VIC 3052, Australia
Adele Preaudet
Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria, VIC 3052, Australia
Tracy Putoczki
Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria, VIC 3052, Australia
Julia Beretov
St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Ewan K. A. Millar
St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Emad El-Omar
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Xiao-Tao Jiang
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Howard Chi Ho Yim
UNSW Microbiome Research Centre, St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW 2052, Australia
Alteration of the gut virome has been associated with colorectal cancer (CRC); however, when and how the alteration takes place has not been studied. Here, we employ a longitudinal study in mice to characterize the gut virome alteration in azoxymethane (AOM)-induced colorectal neoplasia and identify important viruses associated with tumor growth. The number and size of the tumors increased as the mice aged in the AOM treated group, as compared to the control group. Tumors were first observed in the AOM group at week 12. We observed a significantly lower alpha diversity and shift in viral profile when tumors first appeared. In addition, we identified novel viruses from the genera Brunovirus, Hpunavirus that are positively associated with tumor growth and enriched at a late time point in AOM group, whereas members from Lubbockvirus show a negative correlation with tumor growth. Moreover, network analysis revealed two clusters of viruses in the AOM virome, a group that is positively correlated with tumor growth and another that is negatively correlated with tumor growth, all of which are bacteriophages. Our findings suggest that the gut virome changes along with tumor formation and provides strong evidence of a potential role for bacteriophage in the development of colorectal neoplasia.
