Effect of Fibre Supplementation on Mixed-meal Challenge Response
Condition: Health Status
Study type: Interventional

Summary: 
      Improving healthy physiological processes through nutritional intervention, as opposed to
      restoring physiology after disease occurrence, is an important new avenue for the reduction
      of disease burden in the population. A relatively new target for interventions is the gut
      microbiome. Dietary fibre is a nutritional intervention shown to alter gut microbiome and
      function. The present study aims to elucidate the relationship between microbiome modulation
      with dietary fibre and health. In order to assess health improvement, a meal challenge will
      be given to characterize the physiological processes and their resilience to challenge in
      healthy volunteers before and after microbiome modulation.
    

Detailed description: 
      The gut microbiome has been extensively implicated as an organ involved in various
      physiological processes such as nutrient and drug metabolism, microbial protection and
      immunomodulation. The gut microbiome educates the host immune system, promotes homeostasis
      and protects against systemic inflammation, among other things through production of
      short-chain fatty acids (SCFAs). An altered microbiome is also involved in inducing low-grade
      systemic inflammation by translocation of bacterial lipopolysaccharide (LPS) through the
      intestinal lining. Additionally, the gut microbiome produces trimethylamine (TMA), which when
      oxidized to trimethylamine N-oxide (TMAO) is documented as an indicator of endothelial
      dysfunction and cardiovascular health risk. The goal of the present study is to further
      clarify the relationship between the gut microbiome, homeostasis, immunity and health. This
      will be achieved by introducing an intervention known to alter gut microbiome
      characteristics, dietary fibre, and measuring its effect on the gut microbiome on the one
      hand and the response to metabolic challenge on the other.

      Fibre mixtures consisting of indigestible carbohydrates have been shown to alter the
      composition and function of the gut microbiome. Fibre functions as a substrate for
      fermentation, creating SCFAs, and as a food source for bacterial commensals regarded as
      beneficial. Thus, fibre can shift the balance of microbial species in the gut towards
      beneficial commensals and away from potential pathogens. Moreover, these changes in
      composition and function of the microbiome can feasibly affect integrity of intestinal
      lining, TMA production and various other processes, therefore exerting an effect on low-grade
      inflammation, cardiovascular and metabolic health. The gut microbiome can be analysed using
      16s RNA sequencing, quantifying the relative abundance of various bacterial species, and by
      measuring SCFAs in human plasma, quantifying their production by bacteria in the gut. In this
      study, we will integrate a third method to measure the gut microbiome. The I-screen,
      developed by TNO, is a platform in which the in vivo microbiome composition can be mimicked
      in an in vitro system, allowing for experimental analysis of the effects of compounds and
      ingredients on the microbiome. With this method, the processes and conditions affecting
      microbiome composition can be assessed more closely, possibly clarifying specific
      relationships between intervention and microbiome composition.

      The present study aims to assess the effects of this microbiome modulation by evaluating the
      response to a metabolic challenge, quantified through measurement of a metabolic and
      inflammatory biomarker panel to create a composite outcome called 'resilience'. This
      phenotypical flexibility test (PhenFlex, PFT), consisting of a mixed meal with protein, fat
      and glucose, induces a systemic response which when analysed allows for sensitive assessment
      of subtle health benefits in otherwise healthy subjects. Results of the PFT are presented as
      a composite of multiple biomarkers grouped by physiological processes such as inflammation
      and liver metabolism, creating the 'axes' of a 'health space'. Earlier research shows that
      selected dietary products affected inflammatory processes, oxidative stress and metabolism,
      based on dynamic responses after fat load. Other research has shown that the challenge test
      concept is able to reveal previously unidentified correlations between specific nutrients and
      health-related processes, and that decreased phenotypic flexibility as measured by PFT can be
      used to identify people that might benefit from health interventions. Finally, in a human
      volunteer study with whole grain wheat products researchers were able to show a positive
      effect on diverse composite markers of resilience, including low grade inflammation, after 12
      weeks of exchange of refined wheat for whole grain wheat consumption.

      By measuring the effect of our intervention on the gut microbiome with several tools, as well
      as using the challenge concept for quantifying health, this study is well positioned to
      provide insight in the specific mechanisms of interaction between microbiome and host, as
      well as create new evidence-based avenues for the improvement of health.
    

Intervention name(s): placebo; Fibre mixture
Intervention type(s): Other; Dietary Supplement
Intervention description(s): Powder consisting of 13 g of digestible carbohydrates with similar appearance as the investigational fibre mixture.; The study product is a fibre mixture consisting of a mix of 10 g of Acacia Gum and 3 g of carrot fibre taken p.o. o.d. in powder form for a total of approximately 10 g of dietary fibre per day.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Placebo or intervention, wash-out, intervention or placebo
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Health Services Research
Keywords: Fibre; Gut microbiome; Meal challenge; Microvasculature