A Randomized Controlled Trial Of Berberine In The Prevention Of Recurrence After Endoscopic Resection Of Colorectal Adenomas

Colorectal cancer is a common cancer with high incidence,which is seriously harmful to human health,and the incidence has been rising.Colorectal adenoma is a precancerous lesion of colorectal cancer,although evidence exists that reductions in colorectal cancer mortality can be achieved through detection and removal of adenomatous polyps,but the recurrence rate of colorectal adenoma is as high as 30-40%within 3 years after removal.It has been reported that aspirin,COX-2 inhibitors,calcium,vitamin D and folic acid perhaps prevent the recurrence of adenoma,but it is unknown about potential side effects of those drugs,or the dose-benefit ratio is uncertain.Berberine,an isoquinoline alkaloid,extracted from Coptis chinensis,Cortex Phellodendri and other plants.Many clinical research on berberine has revealed its various pharmacological properties such as anti-inflammation,bacteriostasis,improved insulin resistance and protective effect on cancer.Berberine can inhibit the occurrence and development of colorectal cancer by blocking cell cycle,inducing cell apoptosis and anti-inflammation.But it remains to be further verified and discussed whether berberine affects the recurrence and related mechanisms of colorectal adenoma after endoscopic.101 Patients with colorectal adenoma by colonoscopy and pathological diagnosis were enrolled in the department of gastroenterology from March 2015 to December 2017.All the cases were strictly screened according to the admission and exclusion ctriteria.Gender,age,body mass index(BMI),smoking history,and features of colorectal adenoma(number,size,location,pathology of colorectal adenomas)were all recorded at large.All the eligible participants were randomly divided into berberine group(group A)and placebo group(group B),who were treated with berberine hydrochloride 300mg bid(two times daily,300mg each time)or comfort agent 3 tablets bid(two times daily,3 tablets each time)respectively for two years.At the end of 12th and 24th month,colonoscopy,intestinal tumor markers and other related indicators would be performed or tested again in order to compare the differences of adenoma recurrence.The feces were collected and analyzed by 16s rRNA sequencing to evaluate the effect of berberine on the gut microbiota.The results show that there is no significant differences in patient’s characteristics at baseline between berberine group and placebo control group,such as gender,age,BMI,smoking history and features of colorectal adenoma.The recurrence rate of colorectal adenoma in berberine group(14.98%;19.04%)is significantly lower than that in control group(34.09%;46.42%).At the end of 12 months after intervention,according toamplification and sequencing,compared with controls,there is a significant increase in the abundance of the Slacki in berberine group,but there is no significant difference in alpha diversity and beta diversity.Finally,we come to the conclusion that berberine can effectively prevent the recurrence of colorectal adenoma after endoscopic excision.And berberine may inhibit the recurrence of adenoma by regulating the change of gut microbiota.