Effect of probiotic lozenges containing Lactobacillus reuteri on oral wound healing: a pilot study

Abstract

It has been suggested that beneficial bacteria may stimulate wound healing. The aim was to investigate the effect of topical applications of probiotic lactobacilli on the healing of standardised oral wounds. This pilot study employed a randomised, placebo-controlled, double-blind cross-over design. Standardised biopsies were punched in the oral mucosa of 10 healthy volunteers, with and without exposure to two strains of Lactobacilli reuteri administrated as lozenges and topical oil. The healing was scored clinically after 2, 5 and 8 days. The amount of exudate was quantified through filter papers and the levels of selected cytokines and chemokines were determined with multiplex immunoassays. Saliva samples were collected before the biopsy and after healing for determination of oxytocin with ELISA. Subjectively perceived pain and discomfort was reported through a daily logbook. There was a clear tendency of improved healing in test group at the 2-and 5-day check-ups but the difference compared with the placebo intervention was not statistically significant (P=0.08). Higher but non-significant expressions of the tumour necrosis factor (TNF) superfamily ligand members 13 (APRIL) and 13B (BAFF), as well as the chemokine interleukin 8 (IL-8), were displayed in wound exudates from the probiotic group as compared with placebo, particularly after 5 and 8 days. The salivary levels of oxytocin were significantly lower (P<0.05) in the placebo group at the 8-day follow-up. The mean number of days with pain and/or discomfort after the biopsies was similar in both groups. No side-effects were reported. The findings of this pilot study justify a larger clinical trial to elucidate the possible role of probiotic supplements on oral wound healing.

Effects of Lactobacillus reuteri-containing lozenges on healing after surgical removal of mandibular third molars: a randomised controlled trial

“…It should, therefore, be underlined that present findings cannot be generalised to the situation of chronic oral wounds often appearing among immunosuppressed patients and frail elderly. The non-affected concentrations of salivary oxytocin were not supportive to the study of Poutahidis and co-workers (2013), but in agreement with our previous pilot observations (Twetman et al, 2018).…”

“…Furthermore, we noted a tendency to improved healing of Unit, Halland Hospital, 30185 Halmstad, Sweden;2 Department of Clinical Microbiology, Halland Hospital, 30185 Halmstad, Sweden;3 Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, P.O. Box 4064, 141 04 Huddinge, Sweden;4 Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Allé 20, 2200 Copenhagen N, Denmark;dan-ake.valivaara@regionhalland.se standardised oral wounds (punch biopsies) during intake of L. reuteri supplements (Twetman et al, 2018). Most oral wounds are, however, open sockets, following surgical extractions of teeth.…”

Probiotic supplements containing Lactobacillus reuteri does not affect the levels of matrix metalloproteinases and interferons in oral wound healing

“…Total protein concentration, expressed as mg/mL, was analyzed using Bio-Rad DC protein assay (Bio-Rad, Solna, Sweden). The protein levels were measured in duplicates and the levels of MMPs and IFNs were analyzed in single within one analytical run, as previously described [ 13 ].…”

“…Importantly, the participating subjects were exposed to the test or placebo interventions in a randomized order. Furthermore, the volunteers were healthy and well-fed and the compliance with the study protocol was excellent [ 13 ]. As we were unable to demonstrate any significant differences in the amounts of MMP’s and IFN’s between the two interventions, the null hypothesis was accepted.…”

“…Previous research has indicated that probiotic treatment can decrease the expression of IFN-gamma from T-cells [ 11 ] and in saliva [ 12 ]. We have recently investigated L. reuteri in the context of oral wound healing and found elevated levels of ligand members of the tumor necrosis factor (TNF) superfamily, as well as Interleukin 8 in the wound exudate after a standardized punch biopsy [ 13 ]. In this communication, the levels of MMP-1, MMP-2, MMP-3, IFN-alpha2, IFN-beta and IFN-gamma are reported.…”