An exploratory study on the dynamic (microbiological, biochemical and immunological) interactions of the oral ecosystem during induction of mild gingival inflammation*

Individuals have been shown to differ in their vulnerability for oral disease.
In experimental clinical setting, this has been demonstrated where individuals
vary in the degree of gingival inflammation following overgrowth of dental
plaque. We hypothesize this difference is due to differences in the mechanisms
by which the individuals can withstand and/or adapt to the stress conditions
applied in the clinical model and that these mechanisms are of key importance
in our ability to maintain our oral health. We expect that - in analogy of
other biological systems - the mouth has intrinsic mechanisms to maintain or
restore homeostasis following a perturbance. These processes have up to date
gained little attention in research. By examining in detail the dynamic
biological responses of the oral ecosystem in individuals during experimental
gingivitis induction and relating these responses to individual variation in
the inflammatory outcome, it is expected that the biological processes that
contribute to our ability to maintain oral health can be identified. Detailed
insight in these processes may allow the development of novel strategies for
dentists and dental hygienists to promote oral health and prevent of oral
disease in the individual patient. This may include novel diagnostic tool to
provide insight in the vulnerability of an individual for the development of
disease but also may also include novel food and personal care products that
stimulate resilience of the mouth.

To explore the dynamic changes in the microbiological composition (of the
separate niches) of the oral ecosystem upon refraining from oral hygiene for
two weeks compared to baseline and after a one-week resolution phase assessed
with or without the use of erythritol in a systemically healthy adult
population.

This is a single center, challenge intervention, randomized study in
systemically healthy subjects.

The challenge intervention is based on a full mouth experimental gingivitis
protocol (Löe et al., 1965). For this, subjects will be requested to refrain
from any form of oral hygiene for two weeks, resulting in plaque accumulation,
temporarily leading to induction of (mild) gingival inflammation.
To intervene in the composition (and activity) of the oral microbiota prior and
during plaque accumulation, a subgroup (N=25) will receive a nutritional
supplement called erythritol (a food additive known to be a possible stabilizer
of the ecosystem) 6 times a day for 5 weeks, i.e. two weeks prior as well as
two weeks during and one week after the challenge intervention (2 weeks
wash-in, 2 weeks experimental gingivitis, 1 week recovery).

The risks and burden related to this study are judged to be very limited. The
induction of mild (short term, temporarily/reversible) gingival inflammation is
a well-established method without the occurrence of adverse events (Versteeg et
al. 2008). Determination of the clinical parameters are part of standard dental
clinical care. In addition, the collection of samples during the study do not
require invasive procedures. As the outcomes of this study could support oral
health and prevention of oral disease in the individual patient, the very
limited burden and risks for the subjects are considered acceptable.