Secondary bile acid induced intestinal adenoma canceration and its effect on intestinal microflora in Apcmin/+ mice / 中华消化杂志

ABSTRACT

Objective To investigate secondary bile acid induced canceration process of intestinal adenoma and effects on intestinal microflora in Apcmin/+ mice.Methods Forty four-week-old mice (20 Apcmin/+mice and 20 wild-type C57BL/6J mice) were divided into four groupswild-type control group (regular drinking water),wild-type deoxycholic acid (DOC) group (with 0.2 ％ DOC in drinking water),Apcmin/+ control group and Apcmin/+ DOC group.Fecal pellets of Apcmin/+ mice were collected at 0 week and 12 week after administration.The changes of intestinal microflora were analyzed by pyrosequencing.All mice were sacrificed after 12 weeks.The number,size and location of intestinal adenoma were observed.The pathological type of adenoma was evaluated after hematcxylin-eosin (HE) staining.Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry.Cell apoptosis was determined by in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labeling technique (TUNEL).Independent t test was used for the quantitative data comparison between two groups.Results No intestinal tumors were found in the wild-type mice.The total number of intestinal adenoma of Apcmin/+ DOC group significantly increased,compared with that of Apcmin/+ control group (57.00 ± 3.07 vs 21.50± 4.69,t=20.03,P＜0.01),the increase of the adenoma with maximum diameter between 1 to 2 mm was most significant (30.62± 7.73 vs 7.75 ± 4.59,t =8.04,P＜ 0.05),the rate of adenoma canceration also significantly increased compared with that of Apcmin/+ control group.The percentage of PCNA positive cells significantly increased compared with that of Apcmin/+ control group ((90.17 ± 2.14) ％ vs (41.97 ± 4.26) ％,t=31.97,P＜0.01).The percentage of cell apoptosis significantly declined ((1.40± 1.12) ％ vs (7.50 ± 0.65)％,t =14.90,P＜ 0.01).The diversity of intestinal flora of Apcmin/+ DOC group significantly decreased.The ratio of Firmicutes and Bacteroidetes significantly increased compared with control group (0.586 7±0.148 4 vs 0.387 3±0.013 6,t=2.36,P＜0.05).The number of pathogenic bacteria increased in Apcmin/+ DOC group and probiotics significantly decreased.Conclusion DOC can induce intestinal flora imbalance in Apcmin/+ mice and promote intestinal adenoma into adenocarcinoma through increasing tumor cell proliferation and inhibiting cell apoptosis.