A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota
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.
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ω-3 fatty acids have been proposed to restore the eubiotic state in pathological conditions by increasing beneficial bifidobacteria and decreasing enterobacteria, which in turn supports an anti-inflammatory environment through the production of SCFAs and suppression of endotoxemia.
“Indeed, ω-3 fatty acids have been proposed to restore the eubiotic state in pathological conditions by increasing the beneficial bifidobacteria and decreasing enterobacteria, which in turn supports an anti-inflammatory environment through the production of SCFAs and suppression of endotoxemia (81,141).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [81]
In humans, healthier polyunsaturated fatty acids (e.g., omega-3 PUFAs) promote the growth of beneficial bacteria, including butyrate producers such as Lactobacillus, Lachnospira, Roseburia, and Bifidobacterium, and are correlated with higher microbial diversity as well as taxa from the families Lachnospiraceae and Ruminococcaceae.
“In humans, healthier polyunsaturated fatty acids (e.g., omega-3 PUFAs) promote the growth of beneficial bacteria, including butyrate producers such as Lactobacillus, Lachnospira, Roseburia, and Bifidobacterium (81), and are correlated with higher microbial diversity as well as taxa from the families Lachnospiraceae and Ruminococcaceae (82).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [81]
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- Authors
- Watson, H., Mitra, S., Croden, F. C., Taylor, M., Wood, H. M., Perry, S. L., Spencer, J. A., Quirke, P., Toogood, G. J., Lawton, C. L., Dye, L., Loadman, P. M., & Hull, M. A.
- Affiliations
- University of Leeds (GB)
- Leeds General Infirmary (GB)
- University of Bradford (GB)
- Institute of Cancer and Pathology, St James’s University Hospital, University of Leeds, Leeds, UK
- St James's University Hospital (GB)
- Corresponding author
- Hull, Mark A
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-09-26
- Volume
- 67
- Issue
- 11
- Pages
- 1974-1983
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2758490346
- Cited by
- 506
- References
- 39
- Citations by year
- 2026: 42 · 2025: 57 · 2024: 59 · 2023: 71 · 2022: 79 · 2021: 75 · 2020: 64 · 2019: 38 · 2018: 16 · 2017: 4
- FWCI
- 27.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Bradford Scholars (University of Bradford) (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Medical Research Council (MC_G1002465)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- omega-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, dietary supplementation, gut microbiota, fecal microbiota, short-chain fatty acid-producing bacteria, Bifidobacterium, Roseburia, Lactobacillus, red blood cell fatty acids, arachidonic acid, colorectal cancer prevention, administration methods, soft gel capsules
- MeSH terms
- Gastrointestinal Microbiome, Aged, Chromatography, Liquid, Fatty Acids, Feces, Female, Humans, Male, Middle Aged, Mass Spectrometry, Fatty Acids, Omega-3, Polymerase Chain Reaction, Cross-Over Studies, Dietary Supplements, Healthy Volunteers
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