Michael Michael and his research team are looking at the involvement of microRNAs in dietary reduction of cancer risk in Familial Adenomatous Polyposis patients
Familial Adenomatous Polyposis (FAP) is a rare inherited predisposition to colorectal cancer, and requires surgery. Few other interventions are available, so a dietary supplement with proven efficacy would have clinical value. Colonic fermentation of dietary fibre, butyrate is known to play a significant role in bowel health.
To investigate if butyrate can limit adenoma initiation and progression in FAP, the AusFAP trial was designed as a double blind RCT in 120 volunteers with medically diagnosed FAP. Volunteer diets were supplemented with 40g HAMSB/day for a total of 26 weeks, in a cross-over trial with a resistant starch (RS) placebo, then looking at biopsis. To determine the effect of butyrate on gene regulation in both FAP mucosae and polyps, the mRNA profiles of biopsies were compared across treatment groups using mRNA-seq.
This project analysed biopsies to test the effect of butyrate (6 month consumption of butyrylated resistant starch). RNA was prepared from biopsies of polyps (adenomas) or ‘normal’ gut. The relative levels of messenger RNAs was quantified using next generation sequencing.
Six month consumption of butyrylated resistant starch (HAMSB) altered the activity of several genes in both the normal gut lining and polyps of FAP volunteers. Amongst the genes activated in polyps are those associated with apoptosis, or programmed cell death. This supports the notion that butyrate protects against bowel cancer by triggering pre-cancerous cells to die. It is also possible that butyrate suppresses major cell signalling pathways that promote cancer cell growth. These results require verification in larger datasets, and would also benefit from intervention studies in pre-clinical models.
This transcriptomics study adds to a growing body of evidence supporting the benefit of high fibre diets, and especially resistant starches, in preventing colorectal cancer.
