Metabolon Elucidates a Link Between Short Chain Fatty Acids and Colorectal Cancer in Cystic Fibrosis Patients

The Challenge: Understanding Cystic Fibrosis and the Increased Risk of Colorectal Cancer

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CFTR codes for a protein that regulates salt and water transport in and out of cells. In the past, CF was often fatal in childhood, with many children dying before reaching adolescence. However, with advances in medical care, the outlook for people with CF has improved significantly over the past few decades. Today, many individuals with CF can live into adulthood and lead relatively normal lives. Yet, as more individuals with CF are now reaching adulthood, adults with CF seem to have an increased and early risk of malignancy, including a higher incidence of colorectal cancer (CRC). Compared to the general population, CF patients are 5 to 10 times more likely to develop CRC.¹ Unfortunately, the molecular mechanisms underlying the increased risk of CRC in patients with CF are poorly understood.

Metabolon Insight: Metabolomics Analysis of Short Chain Fatty Acids in Adults With and Without Cystic Fibrosis

This study utilized Metabolon’s Short Chain Fatty Acids Targeted Panel to profile colonic aspirates from adults with (n = 21) and without (n = 21) CF undergoing CRC screening.² Metabolon offered this group the most comprehensive solution to characterize and compare gut SCFA composition of adult patients with and without CF and to determine whether SCFAs are associated with colonic adenomas.

The Solution: Associations Between the Microbiome, Short Chain Fatty Acids, and Colon Cancer in CF Patients

Colonic aspirates were first characterized via 16S rRNA sequencing. In line with prior reports, patients with CF had profound alterations in their gut microbiota, including reduced microbial diversity and reductions in several SCFA-producing taxa. CF patients with adenomas had an increased relative abundance of B. fragilis, a pathogen strongly linked to the development of CRC. This alteration was not observed in non-CF patients with adenomas.

Metabolon’s Short Chain Fatty Acids Targeted Panel was also used to characterize colonic aspirates. CF patients had significantly reduced levels of valeric acid (valerate) and caproic acid (hexanoate) compared to non-CF patients. The research group also assessed for associations between gut microbiome composition, metabolite levels, and adenomas in CF patients. CF microbiome composition was found to be significantly associated with isovaleric acid (isovalerate) concentration and the presence of adenomas.

The Outcome: Metabolomics and the Role of Short Chain Fatty Acids in Colorectal Cancer Risk

These findings suggest that the microbiome composition and SCFAs levels in the gut of patients with CF may contribute to the increased risk of CRC in this population. Metabolomics is a powerful tool for studying the role of SCFAs in disease and has the potential to provide new insights and therapeutic targets for a range of conditions. Further studies are needed to elucidate the interplay between SCFAs and microbiota composition and the biological effects of SCFAs in both CF and non-CF populations.