Published online May 14, 2018. doi: 10.3748/wjg.v24.i18.1995
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.
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.