Ageing, colonic health, obesity and the gut microbiota

Abstract

Ageing, obesity and history of adenomatous polyps are recognised risk factors for colorectal cancer (CRC). In recent decades, patterns of colonic microbiota and their major metabolites, the short chain fatty acids (SCFA), have been proposed as potential additional candidate biomarker of CRC risk. For example, Fusobacterium nucleatum, which adheres to colonic enterocytes, stimulates the b-catenin pathway, and reinforces inflammatory responses has been associated with CRC pathogenesis. Within the Biomarkers Of Risk of Colorectal Cancer (BORICC)Follow-Up (BFU) and Biomarkers Of CRC After Bariatric Surgery (BOCABS) Studies, I have investigated relationships between ageing, colonic health (prior history of adenomatous polyps) and obesity and the gut microbiota and SCFA. Stool samples from 219 BORICC Study participants, 26 of whom had paired samples at follow-up (BFU Study), and 30 BOCABS Study participants, including 19 paired pre-and post-bariatric samples, were used. Illumina sequencing of the 16S rRNA bacterial gene and gas chromatography were performed to quantify the microbiota and SCFA, respectively. In the BORICC Study, I observed significantly lower Firmicutes levels in participants with a prior history of polyps (at greater CRC risk). There were no apparent effects of ageing or of obesity on the microbiota when investigated at phylum or genus levels or on bacterial diversity measures (alpha and beta diversity). Faecal concentrations of acetate and of total SCFA were elevated in the older participants as well as the obese participants in all studies. In BORICC Study, participants with a prior history of adenomatous polyps and those who were obese had higher faecal propionate concentrations. Concentrations of the branched-chain SCFA isobutyrate and isovalerate were higher in stool from older people. In summary, altered concentrations of faecal SCFA alterations were associated with ageing, obesity and in those with a prior history of adenomatous polyps. However, there were no associated effects on the abundance or diversity of gut bacteria.