Intestinal bioavailability of marine omega-3 polyunsaturated fatty acids and associated changes to the gut microbiota

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have anti-colorectal cancer properties. The mechanistic pathways by which oral omega-3 PUFA supplementation influences bioavailability along the gut-blood axis remain poorly understood. This thesis aimed to quantify the concentrations/abundance of omega-3 PUFAs in the small intestine and colonic lumina, assess their association with tissue incorporation and evaluate changes in the distal ileal microbiome.
In a clinical study, ileostomy and blood samples were collected in 11 human volunteers with an ileostomy at baseline, after the first oral dose and after the final oral dose of 4g of mixed EPA/DHA 1:1 capsules for a minimum of 28 days. Ileal fluid omega-3 PUFAs concentrations and microbiome changes were measured.
A secondary analysis was conducted on a published cross-over trial in which participants were randomised to 8 weeks’ supplementation with 4g mixed EPA/DHA in capsule or drink formulation, separated by a 12 week ‘washout’ period. Faecal EPA and DHA abundance and its correlation with red cell membrane (rbc) omega-3 PUFA were explored.
Oral supplementation with omega-3 PUFAs for ≥28 days results in an increase in Ileostomy fluid (IF) EPA/DHA, returning to baseline on cessation. There was a statistically significant association with increased rbc EPA/DHA(p<0.05). There was a positive correlation with increased abundance of Bacteroides in the ileal lumen. Secondary analysis of the cross-over trial showed a rise in faecal EPA /DHA with supplementation irrespective of formulation, although capsules reached statistical significance. There was a weak negative correlation between the rise in faecal and rbc EPA/DHA. There was greater individual variability with capsules compared to drinks, but no statistically significant difference between the absolute change from baseline with either formulation.
This integration of luminal, systemic biomarkers and microbiome shifts, offers novel insights on mechanistic pathways of omega-3 PUFA activity. EPA/DHA concentrations could inform future studies with gut fermentation models.