A proof of concept pilot trial of probiotics in symptomatic oral lichen planus (CABRIO).

Erni Marlina,Richard N Goodman,Stephen Porter,Julie A Barber,Rachel Leeson,Valeria Mercadante,Andrew M Smith,Tim Hodgson,Stefano Fedele,Martina Shephard,Roddy Mcmillan

doi:10.1111/odi.14014

Abstract

To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double-blind parallel group controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition. The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p=0.082) after 30days of probiotic consumption. The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials.

Highlights

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, with a global prevalence of 1.01% (Gonzalez- Moles et al, 2020)
The pathogenesis of OLP is believed to involve a dysregulation of the immune system, (Jontell and Holmstrup, 2015; Zucoloto et al, 2019) including presentation of an unknown antigen, T lymphocyte activation and migration, production of pro- inflammatory cytokines and chemokines resulting in sub-epithelial inflammatory infiltrate, keratinocytes damage and disruption of epithelial homeostasis. (Ke et al, 2017; Lu et al, 2015; Marshall et al, 2017) Available evidence suggests that CXCL10 and IFN-γ are key players in OLP-associated inflammation, (Tao et al, 2008) and previous in vitro studies showed that multi-strain probiotics
|2 are capable of suppressing LPS-induced chemokines, including CXCL10, through the blockade in the phosphorylation of the transcription factor STAT1. (Mariman et al, 2014) Clinically the disease presents with reticular hyperkeratotic changes of the oral mucosa, with more than 50% of the affected individuals developing long-standing erosion and ulceration leading to reduced quality of life due to pain and dysfunction. (Osipoff et al, 2020) There remains no curative treatment and management of OLP is aimed at reducing mucosal erosions/ulceration and the associated painful symptoms

Summary

| INTRODUCTION

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, with a global prevalence of 1.01% (Gonzalez- Moles et al, 2020). (Osipoff et al, 2020) There remains no curative treatment and management of OLP is aimed at reducing mucosal erosions/ulceration and the associated painful symptoms This is achieved through the reduction of local T-cell inflammation and related inflammatory cytokines by anti-inflammatory medications, the most commonly used being glucocorticosteroids. (Iheozor-E jiofor et al, 2020; Kaur et al, 2020) A few small and uncontrolled studies have preliminarily assessed the potential beneficial effects of probiotics upon inflammatory diseases of the oral mucosa, evidence remains weak, it has been suggested that the use of probiotics in individuals with oral ulceration of Behcet's disease, recurrent aphthous stomatitis and chemotherapy-related oral mucositis may lead to clinical benefits including reduced number of ulcers, subjective reduction in oral discomfort and reduced severity of oral mucositis. The present report follows the CONSORT 2010 guideline extension to randomised pilot and feasibility trials. (Eldrige et al, 2016)

| METHODS

| RESULTS

Findings

| DISCUSSION