Acute microbial switch study

The gut contains trillions of microbes that produce a large variety of products
that impact host metabolism, immunity and brain health. Recent evidence
indicating that fermentation products from indigestible food compounds, like
dietary fibres or proteins, may impact metabolism and immune status has led to
the awareness that microbial fermentation is instrumental for maintaining
health in humans. More information on the response and interaction of our gut
microbiota to diet and environmental factors, such as physical activity and
medication use, may lead to more effective and targeted approaches in
prevention and management of chronic diseases like obesity, non-alcoholic fatty
liver disease, diabetes, cardiovascular disease and mental disorders. We will
develop a novel methodology that enables the development and evaluation of
ground-breaking interventions targeted on the modulation of the gut microbiome.
To achieve the novel gut-microbial methodology, a whole-body room calorimetry
installation will be redesigned to achieve a *non-invasive real-time in vivo
microbial fermentation chamber*. The system will measure human-expired gut
microbial relevant gases such as methane (CH4), hydrogen (H2) and hydrogen
sulphide (H2S) combined with host energy expenditure and substrate utilization.
It will provide the unique opportunity to measure real-time microbial
fermentation combined with host substrate energy metabolism. This allows the
screening of dynamic gut-microbial response to the impact of amongst others
foods, medication and exercise. Therefore, this system will deliver fundamental
data to better understand the interplay between diet, other environmental
factors and the gut microbial fermentation. Through this, it will be possible
to steer the production of beneficial fermentation products in the intestine
with food products or lifestyle intervention strategies to support gut,
metabolic, immune and brain health. This study is an important part of NWO
Human Measurement Models 2.0 with the aim is to facilitate the development of
new, more efficient human measurement models for health research to ensure that
research results can be applied better and faster in humans. With this
methodology, researchers can test and develop nutritional compounds and
intervention strategies aimed to improve gut microbial health underlying human
health. This will be the first study on real-time, non-invasive gut microbial
fermentation in humans. We will investigate with this study whether we can
determine the switch from proteolytic to saccharolytic fermentation following
ingestion of a dietary fibre mixture in healthy lean and overweight/obese
insulin resistant and/or prediabetic individuals.

In this project we aim to investigate whether we can precisely measure the
changes in fermentation gas patterns after supplementation of a complex fibre
mixture over a 36-hour period in both lean normoglycemic and insulin resistant
and/or prediabetic individuals with overweight/when compared with a placebo.
Additionally, we will investigate whether changes in fermentation patterns will
be directly related to changes in substrate metabolism and metabolites/hormones
in expired air, blood, faeces, and urine.

Double blind, controlled, randomized, crossover design.

Starting from CID1, participants will start a two-day daily consumption of
either a complex dietary fibre mixture: 12 g (3 × 4 g) of long-chain inulin
(Frutafit TEX! Sensus B.V., Roosendaal, The Netherlands) in combination with
9.39 g (3 × 3.13 g (80% resistant starch RS2 (3 × 2.5 g)) granular potato
starch (Avebe, Veendam, The Netherlands) or 11.43 g (3 × 3.81 g) maltodextrin
Glucidex IT 12 (Roquette Freres, Lestrem, France) maltodextrin as a placebo
treatment for two consecutive days.

At the first breakfast in the respiration chamber during the fiber
supplementation period, 500 mg of inulin will be replaced with 500 mg inulin
that is naturally enriched with 13C (DP 3-60, IsoLife, Wageningen, The
netherlands).

all participants will be screened prior to participation and will thereby gain
information about their health status. In the future there can be general
benefits for the public, but the volunteers will have no personal benefit of
participating in the study. The general interest in this study is that there is
currently no methodology to study the kinetics of fermentation in real-time
faithfully. The amounts of long-chain inulin and resistant starch have been
used in previously performed human trials and have been proven safe. In this
study participants may experience the following as a burden. After initial
screening, subjects will have to invest approximately 72 hours in the study
(See table 1). During the study participants will remain in a respiration
chamber. The participant may consider staying in a predefined space for a
prolonged period of time as a burden. 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 and urine samples can be seen as a burden. Receiving a standardized
diet and having to perform a stepping workout at specific timepoints can be
considered as a burden. Lastly having to ingest the fiber supplemen may be
considered as a burden.