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

Watson, H.; Mitra, Suparna; Croden, Fiona; Taylor, Morag; Wood, Henry M.; Perry, Sarah L.; Spencer, Jade; Quirke, Philip; Toogood, Giles J.; Lawton, Clare; Dye, Louise; Loadman, Paul M.; Hull, Mark A.

doi:10.1136/gutjnl-2017-314968

Cited by 391 publications

(276 citation statements)

References 39 publications

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“…While higher SCFA levels in the stool with fibre‐free EN compared to PN have been reported (Sobotka et al , ; Schneider et al , ), the reason for this is unclear. The EN formula provided also contained omega 3 fatty acids, which have recently been associated with increased abundance of butyrate‐producing bacteria in healthy individuals (Watson et al , ), which may be independent of dietary fibre intake (Menni et al , ). Further investigation of the benefit of fibre and omega‐3 fatty acid‐containing EN on clinical outcomes in HPCT is warranted.…”

Section: Discussionmentioning

confidence: 99%

Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post‐allogeneic transplantation

Andersen¹,

Staudacher

Weber³

et al. 2019

Br J Haematol

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Summary Nutrition support is frequently required post‐allogeneic haematopoietic progenitor cell transplantation (HPCT); however, the impact of mode of feeding on the gastrointestinal microbiome has not been explored. This study aimed to determine if there is a difference in the microbiome between patients receiving enteral nutrition (EN) and parenteral nutrition (PN) post‐allogeneic HPCT. Twenty‐three patients received either early EN or PN when required. Stool samples were collected at 30 days post‐transplant and analysed with shotgun metagenomic sequencing. There was no difference in microbial diversity between patients who received predominantly EN (n = 13) vs. PN (n = 10) however patients who received predominantly EN had greater abundance of Faecalibacterium (P < 0·001) and ruminococcus E bromii (P = 0·026). Patients who had minimal oral intake for a longer duration during provision of nutrition support had a different overall microbial profile (P = 0·044), lower microbial diversity (P = 0·004) and lower abundance of faecalibacterium prausnitzii_C (P = 0·030) and Blautia (P = 0·007) compared to patients with greater oral intake. Lower microbial diversity was found in patients who received additional beta lactam antibiotics (P = 0·042) or had a longer length of hospital stay (P = 0·019). Post‐HPCT oral intake should be encouraged to maintain microbiota diversity and, if nutrition support is required, EN may promote a more optimal microbiota profile.

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Section: Discussionmentioning

confidence: 99%

Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post‐allogeneic transplantation

Andersen¹,

Staudacher

Weber³

et al. 2019

Br J Haematol

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“…98 In addition, a recent randomized cross-over trial in 22 middle-aged, healthy volunteers found that 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid separated by a 12-week ‘washout’ period induced a reversible increase in several genera, including Bifidobacterium, Roseburia and Lactobacillus, although the overall α or β diversity did not significantly change. 99 …”

Section: Marine Omega-3 Fatty Acidsmentioning

confidence: 99%

Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention

Song

Chan

2019

Clinical Gastroenterology and Hepatology

243

157

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The substantial burden of colorectal cancer and increasing trend in young adults highlight the importance of lifestyle modification as a complement to screening for colorectal cancer prevention. Several dietary and lifestyle factors have been implicated in the development of colorectal cancer, possibly through the intricate metabolic and inflammatory mechanisms. Likewise, as a key metabolic and immune regulator, the gut microbiota has been recognized to play an important role in colorectal tumorigenesis. Increasing data support that environmental factors are crucial determinants for the gut microbial composition and function, whose alterations induce changes in the host gene expression, metabolic regulation, and local and systemic immune response, thereby influencing cancer development. Here, we review the epidemiologic and mechanistic evidence regarding the links between diet and lifestyle and the gut microbiota in the development of colorectal cancer. We focus on factors for which substantial data support their importance for colorectal cancer and their potential role in the gut microbiota, including overweight and obesity, physical activity, dietary patterns, fiber, red and processed meat, marine omega-3 fatty acid, alcohol, and smoking. We also briefly describe other colorectal cancer-preventive factors for which the links with the gut microbiota have been suggested but remain to be mechanistically characterized, including vitamin D status, dairy consumption, and metformin use. Given limitations in available evidence, we highlight the need for further investigations in the relationship between environmental factors, gut microbiota, and colorectal cancer, which may lead to development and clinical translation of potential microbiota-based strategies for cancer prevention.

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“…128 We have recently reported that mixed ω-3 PUFA supplementation is associated with an increase in short-chain fatty acid (SCFA)-producing bacterial genera such as Lactobacillus and Bifidobacteria in faecal samples. 129 Although SCFA levels are believed to be higher in the caecum and ascending colon than in the distal colon, 130 the SCFA receptor free fatty acid receptor (FFAR) 2, also known as GPR43, is expressed at higher levels in the left colon. 131 Therefore, a valid hypothesis is that differential antineoplastic activity of EPA may relate to increased antineoplastic SCFA-FFAR2 signalling in the distal versus proximal colon.…”

Section: Mechanistic Considerationsmentioning

confidence: 99%

Eicosapentaenoic acid and/or aspirin for preventing colorectal adenomas during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: the seAFOod RCT

et al. 2019

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Background The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer (CRC) chemoprevention, aligned with an excellent safety profile. Objectives The objectives were to determine whether or not EPA prevents colorectal adenomas, either alone or in combination with aspirin, and to assess the safety/tolerability of EPA, in the free fatty acid (FFA) form or as the triglyceride (TG), and aspirin. Design This was a randomised, blinded, placebo-controlled, 2 × 2 factorial trial. Setting The NHS Bowel Cancer Screening Programme (BCSP). Participants Patients (aged 55–73 years) identified as ‘high risk’ (i.e. those who have five or more colorectal adenomas of < 10 mm in size or three or more colorectal adenomas if one is ≥ 10 mm in size) at screening colonoscopy. Interventions The interventions were capsules containing 2000 mg of 99% EPA–FFA or 2780 mg of 90% EPA–TG (equivalent to 2000 mg of FFA) taken daily, or identical placebo capsules; and 300 mg of aspirin taken daily, or an identical placebo, enteric-coated tablet. Both were taken for ≈1 year until surveillance colonoscopy. All participants and staff were unaware of treatment allocation. Main outcome measures The primary outcome was the number of participants with one or more colorectal adenomas [adenoma detection rate (ADRa)] at surveillance colonoscopy. Outcomes were analysed for all participants with observable follow-up data by an ‘at-the-margins’ approach, adjusted for BCSP site and by the need for repeat baseline endoscopy. Secondary outcome measures – these included the number of colorectal adenomas per patient [mean adenomas per patient (MAP)], ‘advanced’ ADRa and colorectal adenoma location (right/left) and type (conventional/serrated). Results Between November 2011 and June 2016, 709 participants were randomised, with 707 providing data (80% male, mean age 65 years). The four treatment groups (EPA + aspirin, n = 177; EPA, n = 179; aspirin, n = 177; placebo, n = 176) were well matched for baseline characteristics. Tissue EPA levels and tolerability were similar for FFA and TG users. There was no evidence of any difference in ADRa between EPA users (62%) and non-users (61%) [risk difference –0.9%, 95% confidence interval (CI) –8.8% to 6.9%] or for aspirin users (61%) versus non-users (62%) (risk difference –0.6%, 95% CI –8.5% to 7.2%). There was no evidence of an interaction between EPA and aspirin for ADRa. There was no evidence of any effect on advanced ADRa of either EPA (risk difference –0.6%, 95% CI –4.4% to 3.1%) or aspirin (risk difference –0.3%, 95% CI –4.1% to 3.5%). Aspirin use was associated with a reduction in MAP [incidence rate ratio (IRR) 0.78, 95% CI 0.68 to 0.90), with preventative efficacy against conventional (IRR 0.82, 95% CI 0.71 to 0.94), serrated (IRR 0.46, 95% CI 0.25 to 0.87) and right-sided (IRR 0.73, 95% CI 0.61 to 0.88) lesions, but not left-sided (IRR 0.85, 95% CI 0.69 to 1.06) adenomas. There was evidence of chemopreventive efficacy of EPA on conventional (IRR 0.86, 95% CI 0.74 to 0.99) and left-sided (IRR 0.75, 95% CI 0.60 to 0.94) adenomas, but not on total MAP (IRR 0.91, 95% CI 0.79 to 1.05) or serrated (IRR 1.44, 95% CI 0.79 to 2.60) or right-sided (IRR 1.02, 95% CI 0.85 to 1.22) adenomas. EPA and aspirin treatment were well tolerated, with excess mild/moderate gastrointestinal (GI) adverse events (AEs) in the EPA alone group. There were six GI bleeding AEs. Conclusion EPA and aspirin treatment were not associated with a reduction in ADRa. However, both agents displayed evidence of chemopreventive efficacy, based on adenoma number reduction, which was specific to adenoma type and location, and is compatible with known anti-CRC activity of aspirin. Limitations Limitations of the trial included the failure to recruit to the target sample size of 853, and an unexpected switch of EPA formulation mid-trial. Future work A future objective should be to understand the mechanism(s) of action of EPA and aspirin using the trial biobank. Established trial infrastructure will enable future trials in the BCSP. Trial registration Current Controlled Trials ISRCTN05926847. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

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

Cited by 391 publications

References 39 publications

Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post‐allogeneic transplantation

Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post‐allogeneic transplantation

Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention

Eicosapentaenoic acid and/or aspirin for preventing colorectal adenomas during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: the seAFOod RCT

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