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

ObjectiveOmega-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...

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Published inGut Vol. 67; no. 11; pp. 1974 - 1983
Main Authors Watson, Henry, Mitra, Suparna, Croden, Fiona C, Taylor, Morag, Wood, Henry M, Perry, Sarah L, Spencer, Jade A, Quirke, Phil, Toogood, Giles J, Lawton, Clare L, Dye, Louise, Loadman, Paul M, Hull, Mark A
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LanguageEnglish
Published England BMJ Publishing Group LTD 01.11.2018
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Abstract ObjectiveOmega-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).DesignA 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.ResultsBoth 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.ConclusionOmega-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 numberISRCTN18662143.
AbstractList 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).OBJECTIVEOmega-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).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.DESIGNA 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.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.RESULTSBoth 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.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.CONCLUSIONOmega-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.ISRCTN18662143.TRIAL REGISTRATION NUMBERISRCTN18662143.
ObjectiveOmega-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).DesignA 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.ResultsBoth 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.ConclusionOmega-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 numberISRCTN18662143.
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). 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. 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 , and 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. 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. ISRCTN18662143.
Author Croden, Fiona C
Spencer, Jade A
Watson, Henry
Wood, Henry M
Hull, Mark A
Taylor, Morag
Perry, Sarah L
Toogood, Giles J
Quirke, Phil
Dye, Louise
Mitra, Suparna
Loadman, Paul M
Lawton, Clare L
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  givenname: Henry
  surname: Watson
  fullname: Watson, Henry
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Biomedical and Clinical Sciences, St James’s University Hospital, University of Leeds, Leeds, UK
– sequence: 2
  givenname: Suparna
  surname: Mitra
  fullname: Mitra, Suparna
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Biomedical and Clinical Sciences, Leeds General Infirmary, University of Leeds, Leeds, UK
– sequence: 3
  givenname: Fiona C
  surname: Croden
  fullname: Croden, Fiona C
  email: M.A.Hull@leeds.ac.uk
  organization: Human Appetite Research Unit (Nutrition and Behaviour Research Group), School of Psychology, University of Leeds, Leeds, UK
– sequence: 4
  givenname: Morag
  orcidid: 0000-0002-3907-1290
  surname: Taylor
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  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Cancer and Pathology, St James’s University Hospital, University of Leeds, Leeds, UK
– sequence: 5
  givenname: Henry M
  orcidid: 0000-0003-3009-5904
  surname: Wood
  fullname: Wood, Henry M
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Cancer and Pathology, St James’s University Hospital, University of Leeds, Leeds, UK
– sequence: 6
  givenname: Sarah L
  surname: Perry
  fullname: Perry, Sarah L
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Biomedical and Clinical Sciences, St James’s University Hospital, University of Leeds, Leeds, UK
– sequence: 7
  givenname: Jade A
  surname: Spencer
  fullname: Spencer, Jade A
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Cancer Therapeutics, University of Bradford, Bradford, UK
– sequence: 8
  givenname: Phil
  surname: Quirke
  fullname: Quirke, Phil
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Cancer and Pathology, St James’s University Hospital, University of Leeds, Leeds, UK
– sequence: 9
  givenname: Giles J
  surname: Toogood
  fullname: Toogood, Giles J
  email: M.A.Hull@leeds.ac.uk
  organization: Department of Hepatobiliary Surgery, St James’s University Hospital, Leeds, UK
– sequence: 10
  givenname: Clare L
  surname: Lawton
  fullname: Lawton, Clare L
  email: M.A.Hull@leeds.ac.uk
  organization: Human Appetite Research Unit (Nutrition and Behaviour Research Group), School of Psychology, University of Leeds, Leeds, UK
– sequence: 11
  givenname: Louise
  surname: Dye
  fullname: Dye, Louise
  email: M.A.Hull@leeds.ac.uk
  organization: Human Appetite Research Unit (Nutrition and Behaviour Research Group), School of Psychology, University of Leeds, Leeds, UK
– sequence: 12
  givenname: Paul M
  surname: Loadman
  fullname: Loadman, Paul M
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Cancer Therapeutics, University of Bradford, Bradford, UK
– sequence: 13
  givenname: Mark A
  orcidid: 0000-0001-7414-1576
  surname: Hull
  fullname: Hull, Mark A
  email: M.A.Hull@leeds.ac.uk
  organization: Institute of Biomedical and Clinical Sciences, St James’s University Hospital, University of Leeds, Leeds, UK
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28951525$$D View this record in MEDLINE/PubMed
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Keywords fatty acid
colorectal cancer
bacteria
nutritional supplement
omega-3
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Snippet ObjectiveOmega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal...
Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal...
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StartPage 1974
SubjectTerms Aged
Arachidonic acid
Beverages
Cancer
Carcinogenesis
Chromatography, Liquid
Colorectal cancer
Cross-Over Studies
Diarrhea
Diet
Dietary Supplements
Docosahexaenoic acid
Eicosapentaenoic acid
Erythrocytes
Fatty acids
Fatty Acids - blood
Fatty Acids, Omega-3 - therapeutic use
Feces - microbiology
Female
Fish oils
Functional foods & nutraceuticals
Gastrointestinal Microbiome - drug effects
Healthy Volunteers
Humans
Hypotheses
Intervention
Intestinal microflora
Intestine
Liquid chromatography
Male
Mass Spectrometry
Mass spectroscopy
Metabolism
Metabolites
Microbiomes
Microbiota
Middle Aged
Nutrition research
Ostomy
Polymerase Chain Reaction
Polyunsaturated fatty acids
rRNA 16S
Title A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota
URI https://gut.bmj.com/content/67/11/1974.full
https://www.ncbi.nlm.nih.gov/pubmed/28951525
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Volume 67
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