Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2018; 24(18): 1995-2008
Published online May 14, 2018. doi: 10.3748/wjg.v24.i18.1995
Microbiota modification by probiotic supplementation reduces colitis associated colon cancer in mice
Maria Carolina S Mendes, Daiane SM Paulino, Sandra R Brambilla, Juliana A Camargo, Gabriela F Persinoti, José Barreto C Carvalheira
Maria Carolina S Mendes, Daiane SM Paulino, Sandra R Brambilla, Juliana A Camargo, José Barreto C Carvalheira, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil
Gabriela F Persinoti, Brazilian Bioethanol Science and Technology Laboratory (CTBE), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, São Paulo 13083-970, Brazil
Author contributions: Mendes MC and Carvalheira JB designed research; Mendes MC, Paulino DS, Brambilla SR and Camargo JA performed research; Mendes MC and Carvalheira JB analysed data; Persinoti GF analysed data generated by microbiome analysis; Mendes MC and Carvalheira JB wrote the paper; all authors revised and agreed with the final version of this article.
Supported by São Paulo Research Foundation (FAPESP, Brazil, No. 07607-8/2013); and National Research Council (CNPq, No. 150127/2016-2, No. 306821/2010-9).
Institutional animal care and use committee statement: The Ethics Committee on Animal Use (CEUA) of UNICAMP approved the project, according to protocol no. 2761-1.
Conflict-of-interest statement: No potential conflicts of interest were disclosed.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: José Barreto C Carvalheira, MD, PhD, Associate Professor, Department of Internal Medicine, FCM-State University of Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil.
Telephone: +55-19-35219589 Fax: +55-19-35218925
Received: March 6, 2018
Peer-review started: March 7, 2018
First decision: April 3, 2018
Revised: April 13, 2018
Accepted: April 23, 2018
Article in press: April 23, 2018
Published online: May 14, 2018

To investigate the effect of probiotic supplementation during the development of an experimental model of colitis associated colon cancer (CAC).


C57BL/6 mice received an intraperitoneal injection of azoxymethane (10 mg/kg), followed by three cycles of sodium dextran sulphate diluted in water (5% w/v). Probiotic group received daily a mixture of Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum. Microbiota composition was assessed by 16S rRNA Illumina HiSeq sequencing. Colon samples were collected for histological analysis. Tumor cytokines was assessed by Real Time-PCR (Polymerase Chain Reaction); and serum cytokines by Multiplex assay. All tests were two-sided. The level of significance was set at P < 0.05. Graphs were generated and statistical analysis performed using the software GraphPad Prism 5.0. The project was approved by the institutional review board committee.


At day 60 after azoxymethane injection, the mean number of tumours in the probiotic group was 40% lower than that in the control group, and the probiotic group exhibited tumours of smaller size (< 2 mm) (P < 0.05). There was no difference in richness and diversity between groups. However, there was a significant difference in beta diversity in the multidimensional scaling analysis. The abundance of the genera Lactobacillus, Bifidobacterium, Allobaculum, Clostridium XI and Clostridium XVIII increased in the probiotic group (P < 0.05). The microbial change was accompanied by reduced colitis, demonstrated by a 46% reduction in the colon inflammatory index; reduced expression of the serum chemokines RANTES and Eotaxin; decreased p-IKK and TNF-α and increased IL-10 expression in the colon.


Our results suggest a potential chemopreventive effect of probiotic on CAC. Probiotic supplementation changes microbiota structure and regulates the inflammatory response, reducing colitis and preventing CAC.

Keywords: Intestinal microbiota, Chemoprevention, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum

Core tip: Intestinal microbiota has an essential role in carcinogenesis, acting in promotion of inflammation, proliferation and neoplastic progression. Probiotic supplementation is an alternative means of favourably modulating the intestinal microbiota. In this study, we investigate the effect of supplementation with a Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum mixture during the development of an experimental model of colitis-associated colon cancer. Probiotic supplementation on colorectal cancer changed the microbiota and reduced inflammation in the colon, probably by regulating the inflammatory response, and reducing inflammatory cell infiltration by lowering chemokine expression, thus preventing colitis.