Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer by modulating the intestinal microbiota

// Minna Wu 2, 3, * , Yaqi Wu 2, * , Baoguo Deng 2 , Jinsong Li 4 , Haiying Cao 2 , Yan Qu 2 , Xinlai Qian 5 , Genshen Zhong 1, 3 1 Laboratory of Cancer Biotherapy, Institute of Neurology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China 2 College of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, China 3 Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China 4 Department of Pathology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China 5 Department of Pathology, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China * These authors have contributed equally to this work Correspondence to: Genshen Zhong, email: zhonggs@xxmu.edu.cn Keywords: isoliquiritigenin, gut, microbiota, AOM/DSS, colitis-associated colorectal cancer Received: February 12, 2016 Accepted: October 26, 2016 Published: November 15, 2016 ABSTRACT Imbalances in intestinal bacteria correlate with colitis-associated colorectal cancer (CAC). Traditional Chinese medicines have been used to adjust the gut microbiota, and isoliquiritigenin (ISL), a flavonoid extracted from licorice, has shown antitumor efficacy. In this study, the effects of ISL on CAC development and the gut microbiota were evaluated using an azoxymethane and dextran sulphate sodium (AOM/DSS)-induced mouse model of CAC (CACM). Histopathological analysis suggested that ISL reduced tumor incidence in vivo . Moreover, high-throughput sequencing and terminal restriction fragment length polymorphism (T-RFLP) studies of the bacterial 16S rRNA gene revealed that the structure of the gut microbial community shifted significantly following AOM/DSS treatment, and that effect was alleviated by treatment with high-dose ISL (150 mg/kg). Compared to the microbiota in the control mice (CK), the levels of Bacteroidetes decreased and the levels of Firmicutes increased during CAC development. ISL reversed the imbalance at the phylum level and altered the familial constituents of the gut microbiota. Specifically, the abundance of Helicobacteraceae increased after treatment with high-dose ISL, while the abundance of Lachnospiraceae and Rikenellaceae decreased. At the genus level, ISL reduced the abundance of opportunistic pathogens ( Escherichia and Enterococcus ), and increased the levels of probiotics, particularly butyrate-producing bacteria ( Butyricicoccus , Clostridium, and Ruminococcus ). Thus, ISL protects mice from AOM/DSS-induced CAC, and ISL and the gut microbiota may have synergistic anti-cancer effects.