Abstract

Recurrent aphthous stomatitis (RAS) is the most common disease of the oral mucosa, and it has been recently associated with bacterial and fungal dysbiosis. To study this link further, we investigated microbial shifts during RAS manifestation at an ulcer site, in its surroundings, and at an unaffected site, compared with healed mucosa in RAS patients and healthy controls. We sampled microbes from five distinct sites in the oral cavity. The one site with the most pronounced differences in microbial alpha and beta diversity between RAS patients and healthy controls was the lower labial mucosa. Detailed analysis of this particular oral site revealed strict association of the genus Selenomonas with healed mucosa of RAS patients, whereas the class Clostridia and genera Lachnoanaerobaculum, Cardiobacterium, Leptotrichia, and Fusobacterium were associated with the presence of an active ulcer. Furthermore, active ulcers were dominated by Malassezia, which were negatively correlated with Streptococcus and Haemophilus and positively correlated with Porphyromonas species. In addition, RAS patients showed increased serum levels of IgG against Mogibacterium timidum compared with healthy controls. Our study demonstrates that the composition of bacteria and fungi colonizing healthy oral mucosa is changed in active RAS ulcers, and that this alteration persists to some extent even after the ulcer is healed.

Highlights

  • Recurrent aphthous stomatitis (RAS) is one of the most common diseases of the oral mucosa [1]

  • We focused on the overall composition of oral microbiota isolated from five distinct sites in the oral cavity, namely, lower labial mucosa (LL), lower jaw mucosa (LM), tongue (T), upper jaw mucosa (UM), and buccal mucosa (CH)

  • Bacterial alpha diversity at all five sites of oral cavity together was characterized by significantly more operational taxonomic units (OTUs) (Number of OTUs) with a higher, yet not significantly so, number of rare OTUs (Chao1) in Active and Passive RAS cohorts over healthy controls

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Summary

Introduction

Recurrent aphthous stomatitis (RAS) is one of the most common diseases of the oral mucosa [1]. It is estimated that approximately a quarter of the general population may suffer from RAS [2]. It can affect otherwise healthy individuals or manifest as a comorbidity of many inflammatory diseases [3]. No adequate therapy is available and patients suffer from the discomfort caused by painful ulcerations. The etiology of RAS remains unknown, but it is generally accepted that immunological, genetic, and environmental factors of local and systemic origin are involved [4,5]. Changes in microbiota composition have been identified as one of the important environmental factors [6]

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