Omega 3 and Fibre Intervention Study to Improve Metabolic Health

Diet and nutrition are key determinants of chronic disease. However, additional information is needed on which bioactive compounds and in what amounts they should be consumed to obtain a given health benefit. One of the biggest recent breakthroughs in science has been realisation of the importance of the contents, function and homeostasis of the gut microbiome in human health.

Dietary fibre: The influence of diet on the microbiome is illustrated by vast differences across cultures where African communities who have a plant based diet consume 7-fold more fibre compared with the West obtaining more of their energy requirements via utilization of gut microbiota. Hunter-gatherers have been shown to have 30-40% greater numbers and diversity of species than Western populations. Also, a multigenerational murine study showed a Western diet was responsible for depletion of microbiota diversity. Diversity is emerging as the common marker of good gut health across populations and related to production of beneficial short chain fatty acids (SCFAs). The fermentation of dietary fibre changes the profile of microbial-derived metabolites within the GI tract, most importantly SCFAs. Low fibre intake results in reduced production of SCFAs and also shifts the gastrointestinal (GI) microbiota metabolism to the utilization of less favourable nutrients, leading to the production of potentially detrimental metabolites derived from the fermentation of amino acids. Prevention of the generation of such metabolites through dietary fibre is one of the main mechanisms for the prevention of colon cancer. There is considerable observational evidence that fibre intake is beneficial for human health from observational epidemiological studies. However, findings from intervention studies are less consistent. The variability in human intervention studies could also arise from the highly inter-individualized responses of the human GI microbiome to dietary fibres providing a rationale for the individualization of dietary fibre applications.

Omega 3 fatty acids: In humans, omega-3 fatty acids are readily incorporated into cell membranes resulting in increased cell fluidity, which may improve glucose transport. Additionally, omega-3 supplementation enhances resting fat oxidation and glycogen storage, potentially contributing to improved insulin sensitivity. Omega-3 supplementation may also reduce cardiovascular disease risk by reducing circulating very-low-density lipoproteins (LDL), triacylglycerols and free fatty acids (FFA). It also has additional anti-inflammatory and antithrombotic properties. Previously published data by the investigators suggest the potential use of omega-3 supplementation to improve the microbiome composition. Although trials of supplements are inconsistent, current recommended daily intake for omega-3 is 250 mg (active EPA and DHA) for the general population and higher for patients with cardiovascular disease.

The study will be a proof of concept mechanistic study that will show to what extent omega-3 fatty acid supplementation adds to the benefits of a probiotic intervention in terms both of microbiome diversity and composition and of SCFA production. Moreover, it will show whether this results in measurable improvements in other markers of fatty acid metabolism and in the balance of various T-cell lineages some of which are pro-inflammatory and others which are anti-inflammatory. In this study we will test if 1) intake of fibre induces an increase in microbiome diversity, increased SCFA production in the gut and less inflammatory T-cell composition 2) omega-3 supplementation provides a comparable benefit in terms of microbiome diversity and cardiometabolic improvement to that supplied by fibre.

The study will be a randomised controlled intervention study in which participants will be grouped into two different treatment arms. Randomisation will control for equal distribution of key characteristics that may confound between group comparisons and will be assessed by analysis of baseline data.

80 participants over the age of 18 years will be recruited from the TwinsUK database.The total length of the dietary intervention will be 6 weeks with an initial visit at baseline, and one final visit at 6 weeks.