A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota

Gut. 2018 Nov;67(11):1974-1983. doi: 10.1136/gutjnl-2017-314968. Epub 2017 Sep 26.

Abstract

Objective: Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22).

Design: A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry.

Results: Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects.

Conclusion: Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure.

Trial registration number: ISRCTN18662143.

Keywords: bacteria; colorectal cancer; fatty acid; nutritional supplement; omega-3.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chromatography, Liquid
  • Cross-Over Studies
  • Dietary Supplements
  • Fatty Acids / blood
  • Fatty Acids, Omega-3 / therapeutic use*
  • Feces / microbiology*
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Healthy Volunteers
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Polymerase Chain Reaction

Substances

  • Fatty Acids
  • Fatty Acids, Omega-3

Associated data

  • ISRCTN/ISRCTN18662143