Gut microbial community and host intestinal gene expression with combined fish oil and soluble corn fiber compared with corn oil and maltodextrin: A randomized crossover trial in healthy older individuals

Abstract

Background: Concurrent consumption of dietary fiber and n-3 polyunsaturated fatty acids reduces colon tumor formation. However, their combined effects on colorectal cancer risk remain unexplored in human trials.

Objectives: This study investigated the synergistic effects of fish oil (FO) and fermentable fiber on the gut transcriptional profiles and microbiome composition in older adults.

Methods: In a randomized controlled crossover pilot study, 30 adults (ages 50-75 y), received fermentable fiber (33 g/d soluble corn fiber; SCF) plus eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA as FO, 7.7 g/d) or a comparator (similar doses of maltodextrin plus corn oil; MD + CO) for 30 d, followed by a 60-d washout period before crossing over to the alternate intervention. Serum phospholipid fatty acids, stool exfoliome [ribonucleic acid sequencing (RNAseq)], microbiome (16S ribosomal ribonucleic acid gene sequencing), butyrate kinase (but) gene abundance (digital droplet polymerase chain reaction), and fecal short-chain fatty acids were analyzed. Linear mixed models were used for the majority of outcome analyses. Differential expression and pathway enrichment analyses were applied to RNAseq data, whereas microbiome diversity was assessed using α and β diversity.

Results: Serum EPA and DHA concentrations were higher after SCF + FO than MD + CO supplementation [EPA: β = 0.51; 95% confidence interval: 0.31, 0.72; DHA: β = 0.18; 95% confidence interval: 0.10, 0.27; P < 0.0001]. Analysis of host gut transcriptional networks revealed that SCF + FO supplementation inhibited the glucose-insulin receptor-phosphatidylinositol-3 kinase-signaling axis. Microbiome analysis revealed significant intervention differences in β-diversity (F = 4.4, R² = 0.08, P = 0.001), and 27 of 73 genera analyzed, several known short-chain fatty acid producers, differed between the 2 interventions (false discovery rate <0.05). Abundance of the but gene from Roseburia sp (P < 0.001) and the genera Roseburia (P = 0.006) were lower in the SCF + FO compared to MD + CO intervention, although fecal butyrate concentrations did not differ.

Conclusions: Thirty-day supplementation of SCF + FO compared with MD + CO showed significant shifts in intestinal cell pathways relevant to colorectal cancer with concomitant differences in gut microbial community structure and butyrate-producing taxa.

Keywords: colorectal cancer; dietary fiber; exfoliome; fish oil; gut microbiome.