The effects of 2*-fucosyllactose and resistant starch on acetate production and human substrate metabolism

The gut microbiota is being increasingly recognized as an important factor in
fat distribution, insulin sensitivity and glucose and lipid metabolism.
Accordingly, the intestinal microbiota could play an important role in the
development of obesity and diabetes. One of the important functions of the
human microbiota is the fermentation of indigestible carbohydrates, i.e.
dietary fiber or resistant starches. The major products of this saccharolytic
fermentation process are short-chain fatty acids (SCFA). Of note, several
rodent in vivo studies showed that SCFA supplementation and enhanced SCFA
production due to dietary fiber supplementation prevented diet-induced obesity
and insulin resistance. We previously demonstrated in humans that the site of
administration of SCFA is of major importance in humans. Here we concluded that
increasing the availability of the SCFA acetate in the distal colon is
necesssary to elicit beneficial effects on metabolic health. Furthermore,
present literature suggests that the microbial acetate production and its
metabolism differ between lean insulin sensitive and overweight/obese insulin
resistant individuals.
Therefore, we hypothesize(1) that increasing the acetate availability in the
distal colon will increase circulating acetate concentration and promote
substrate and energy metabolism, and (2) that in a disturbed metabolic
phenotype these effects are less pronounced, the following objective will be
addressed:

In one of our previous study we demonstrated that enhanced acetate availability
in the distal, but not proximal, colon promote fat oxidation, energy
expenditure and parameters of substrate and energy metabolism in healthy
normoglycaemic men. In addition, present literature provides indication that
acetate elicits differential effect on substrate and energy metabolism based on
the metabolic phenotype.
Based on our hypothesis, which is (1) that increasing the acetate availability
in the distal colon will increase circulating acetate concentration and promote
substrate and energy metabolism, and (2) that in a disturbed metabolic
phenotype these effects are less pronounced, the following objective will be
addressed:
We will investigate effects of acute supplementation of 2-FL with and without
resistant starch on faecal and blood plasma acetate availability and markers of
substrate and energy metabolism during overnight fasted conditions and after a
high-fat meal in two different metabolic phenotypes. We are interested in
whether fiber supplementation leads to different SCFA production rates and
consequent differences in metabolic outcomes in healthy, lean vs.
overweight/obese, prediabetic individuals.

Double blind, placebo-controlled, randomized, crossover design.

The day before each visit, participants consume one of the supplements with
standardized meals:
1. Placebo: 11.43 g (3 x 3.81 g) maltodextrin Glucidex IT 12 (Roquette Freres,
Lestrem, France) (43.43 kcal/d)
2. 2-FL: 12 g (3 x 4 g) 2*-fucosyllactose (FrieslandCampina Domo, Netherlands)
with 5.43.g (3 x 1.81 g) maltodextrin to make it isocaloric (43.43 kcal/d).
3. 2-FL + RS: 12 g (3 x 4 g) 2*-fucosyllactose (FrieslandCampina Domo,
Netherlands) in combination with 9.375 g (3 x 3.125 g (80% resistant starch (3
x 2.5 g)) granular potato starch (Avebe, Veendam, The Netherlands) (43.43
kcal/d).

All participants will be screened before participation and thereby receive
information about their health status. In the future there can be general
health benefits for the public, but the volunteers will have no personal
benefits by participating in the study. The general interest of this study is
that there have never been human intervention studies investigating the
supplementation of fermentable carbohydrate mixtures in different metabolic
phenotypes and their effects on SCFA concentrations and on their substrate and
energy metabolism. The amounts of 2-FL and resistant starch used in this study
are previously used in several human trials and have been proved to be safe.
In this study the volunteers may experience the following as a burden. After
initial screening, subjects will have to invest approximately 18 hours in the
study. During the study, blood will be collected via a venous catheter.
Venepunctures can occasionally cause a local hematoma or bruise to occur. Some
participants report pain during venepuncture. Also the collection of stool
samples can be seen as a burden.