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A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota
  1. Henry Watson1,
  2. Suparna Mitra2,
  3. Fiona C Croden3,
  4. Morag Taylor4,
  5. Henry M Wood4,
  6. Sarah L Perry1,
  7. Jade A Spencer5,
  8. Phil Quirke4,
  9. Giles J Toogood6,
  10. Clare L Lawton3,
  11. Louise Dye3,
  12. Paul M Loadman5,
  13. Mark A Hull1
  1. 1 Institute of Biomedical and Clinical Sciences, St James’s University Hospital, University of Leeds, Leeds, UK
  2. 2 Institute of Biomedical and Clinical Sciences, Leeds General Infirmary, University of Leeds, Leeds, UK
  3. 3 Human Appetite Research Unit (Nutrition and Behaviour Research Group), School of Psychology, University of Leeds, Leeds, UK
  4. 4 Institute of Cancer and Pathology, St James’s University Hospital, University of Leeds, Leeds, UK
  5. 5 Institute of Cancer Therapeutics, University of Bradford, Bradford, UK
  6. 6 Department of Hepatobiliary Surgery, St James’s University Hospital, Leeds, UK
  1. Correspondence to Professor Mark A Hull, Institute of Biomedical & Clinical Sciences, St James’s University Hospital, University of Leeds, Leeds, LS9 7TF, UK; M.A.Hull{at}


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.

  • bacteria
  • colorectal cancer
  • fatty acid
  • nutritional supplement
  • omega-3

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  • 24 HW and SM are joint first authors.

  • Contributors HW and FCC performed the randomised study and collected samples. HW, SM, MT, HMW, SP, JAS and PL analysed samples and contributed to data analysis. MH, LD, CLL, GJT and PQ designed the study and obtained funding. MH and SM wrote the paper, which was reviewed and approved by all authors.

  • Funding This study was funded by an unrestricted scientific grant from Smartfish AS. Fatty acid analysis was supported by the Yorkshire Experimental Cancer Medicine Centre. PQ is supported by an NIHR Senior investigator award and by Yorkshire Cancer Research (YCR) as the YCR Centenary Professor of Pathology.

  • Competing interests MH acts as a consultant advisor for Thetis Pharmaceuticals.

  • Ethics approval South Yorkshire research ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.