The effect of omega-3 polyunsaturated fatty acids on short-chain fatty acid production and the gut microbiome in an <i>in vitro</i> colonic fermentation model

Oral administration of omega-3 polyunsaturated fatty acids (PUFAs) to rodents and humans is associated with an increase in gut bacteria that are predicted to synthesise short-chain fatty acids (SCFAs). We tested the hypothesis that physiological levels of omega-3 PUFAs in the distal intestinal lumen (1-50 μg/mL) are associated with increased SCFA synthesis in an <i>in vitro</i> fermentation model using faecal slurry from 10 healthy participants (mean age 30 years), with and without exogenous dietary fibres. SCFAs were measured by gas chromatography-flame ionisation detection (<i>n</i> = 10), and changes in bacterial composition were analysed by shotgun metagenomic sequencing (<i>n</i> = 6). In the presence of omega-3 PUFAs, there was a mean 9.3% (no inulin; <i>P</i> = 0.03) and 19.3% (+ 0.01 mg/mL inulin; <i>P</i> = 0.01) increase in total SCFA concentration at 24 h compared with paired control fermentations. Omega-3 PUFAs had a limited effect on the fermentation model microbiome in the absence of inulin. However, omega-3 PUFAs (50 μg/mL) were associated with increased abundance of <i>Bifidobacteriaceae</i> compared with paired control fermentations, if inulin (0.01 mg/mL) was present. Prebiotic activity of omega-3 PUFAs drives SCFA synthesis in an <i>in vitro</i> colonic fermentation model and is augmented by the soluble fibre inulin.