The clinical evaluation of the effectiveness of two oral probiotic strains on gingival health.

In the current study we will evaluate the effectiveness of two well defined
probiotic strains, Lactobacillus paracasei LPc-G110 (CCTCC M 2013691) and
Lactobacillus plantarum GOS42 (DSM 32131), in strengthening the oral ecosystem.
These strains were selected from a panel of probiotic strains as the first
mentioned was most potent in reducing the proportions of several anaerobic
genera in ex vivo oral biofilms and the second was very effective in modulating
the immune response in a model for gingival immune reactions. After
supplementing the oral ecosystem with these probiotics or a placebo for 14
days, we will examine the (strengthened) resilience of the oral ecosystem using
a two-week experimental gingivitis model by following the dynamics of clinical,
immunological and microbial parameters. After experimental gingivitis, the
volunteers will resume their normal oral hygiene routine and stop using the
food ingredient. Two weeks later, when the effects of the experimental
gingivitis have been reversed, we will examine the oral ecosystem once more to
assess to what extent the modulating effects of L. paracasei and L. plantarum
on the oral microbiome/ecosystem are still present.

The primary objective is to evaluate clinically the effectiveness of two oral
probiotic strains, compared with a placebo-group, on the gingival health during
a two-week wash-in phase followed by a two-week period refraining from oral
hygiene and a two-week wash-out phase. The secondary objective is to explore
the dynamics of immunological and microbiological aspects of the oral cavity
for the duration of the wash-in phase, the experimental gingivitis phase and
the wash-out phase concerning the use of the two oral probiotic strains
compared with the placebo-group.

This study is a single-centre, intervention, double-blind, parallel group (3)
randomised, placebo-controlled clinical trial.

Subjects are instructed to use one lozenge, 3 times daily after each meal, with
the probiotic Lactobacillus plantarum (group A), with the probiotic
Lactobacillus paracasei (group B) or lozenges without probiotics (placebo
group). The challenge intervention is based on a full mouth experimental
gingivitis protocol. 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.

The risks and burden related to this study are judged to be very limited. The
time burden per research visit is at most 30 minutes. The induction of mild
(short term, temporarily/reversible) gingival inflammation is a
well-established method. The mild inflammatory status is completely reversible
without long term risk or effects on dental health.
Determination of the clinical parameters are part of standard dental clinical
care. In addition, the collection of samples (saliva, plaque) during the study
do not require invasive procedures. The probiotic strains, L. paracasei and L.
plantarum, are present in various fermented food products and comply with the
Qualified Presumption of Safety (QPS) status given by European Food Safety
Authority (EFSA). Besides they are both available in many over-the-counter
probiotic food ingredients targeted at gut health and oral health.
There is no direct benefit for the participants. The aim of the food
ingredients are to sustain oral health in healthy individuals, therefore the
effects of these ingredients are examined in an orally and systemically healthy
population. As the outcomes of this study could support oral health and prevent
oral disease, the very limited burden for the subjects is considered
acceptable.