Background: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (theWinnie-APCMin/+) combining inflammation and genetics. Methods: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/++ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother’s genetics in ACF development, the large intestines of APCMin/++ mice born from wild type mice were investigated by histological analysis at 8 weeks. Results: ACF development in 8-week-old Winnie-APCMin/++ mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/++ hosts leads to an increased rate of ACF development. Conclusions: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring.

Dysbiosis triggers ACF development in genetically predisposed subjects

De Santis S.;Verna G.;Cavalcanti E.;Calabrese F. M.;De Angelis M.
;
2021

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (theWinnie-APCMin/+) combining inflammation and genetics. Methods: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/++ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother’s genetics in ACF development, the large intestines of APCMin/++ mice born from wild type mice were investigated by histological analysis at 8 weeks. Results: ACF development in 8-week-old Winnie-APCMin/++ mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/++ hosts leads to an increased rate of ACF development. Conclusions: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/359757
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