Oral Phenotype and Salivary Microbiome of Individuals With Papillon-Lefèvre Syndrome.

Giulia Melo Lettieri,Luander Medrado Santiago,Nailê Damé-Teixeira,Laudimar Alves De Oliveira,Giancarlo Crosara Lettieri,Luiz Gustavo Dos Anjos Borges,Loise Pedrosa Salles,Letícia Marconatto

doi:10.3389/fcimb.2021.720790

Abstract

Papillon–Lefèvre syndrome (PLS) is an autosomal recessive rare disease, main characteristics of which include palmoplantar hyperkeratosis and premature edentulism due to advanced periodontitis (formerly aggressive periodontitis). This study aimed to characterize the oral phenotype, including salivary parameters, and the salivary microbiome of three PLS sisters, comparatively. Two sisters were toothless (PLSTL1 and PLSTL2), and one sister had most of the teeth in the oral cavity (PLST). Total DNA was extracted from the unstimulated saliva, and the amplicon sequencing of the 16S rRNA gene fragment was performed in an Ion PGM platform. The amplicon sequence variants (ASVs) were obtained using the DADA2 pipeline, and the taxonomy was assigned using the SILVA v.138. The main phenotypic characteristics of PLS were bone loss and premature loss of primary and permanent dentition. The PLST sister presented advanced periodontitis with gingival bleeding and suppuration, corresponding to the advanced periodontitis as a manifestation of systemic disease, stage IV, grade C. All three PLS sisters presented hyposalivation as a possible secondary outcome of the syndrome. Interestingly, PLST salivary microbiota was dominated by the uncultured bacteria Bacterioidales (F0058), Fusobacterium, Treponema, and Sulfophobococcus (Archaea domain). Streptococcus, Haemophilus, and Caldivirga (Archaea) dominated the microbiome of the PLSTL1 sister, while the PLSTL2 had higher abundances of Lactobacillus and Porphyromonas. This study was the first to show a high abundance of organisms belonging to the Archaea domain comprising a core microbiome in human saliva. In conclusion, a PLST individual does have a microbiota different from that of the periodontitis’ aggressiveness previously recognized. Due to an ineffective cathepsin C, the impairment of neutrophils probably provided a favorable environment for the PLS microbiome. The interactions of Bacteroidales F0058, Caldivirga, and Sulfophobococcus with the microbial consortium of PLS deserves future investigation. Traditional periodontal therapy is not efficient in PLS patients. Unraveling the PLS microbiome is essential in searching for appropriate treatment and avoiding early tooth loss.

Highlights

Papillon and Lefèvre first described the Papillon–Lefèvre syndrome (PLS) in 1924 (Papillon and Lefevre, 1924)
The phenotypic characteristics observed in the three patients were bone loss and the early loss of primary and permanent dentition, for the PLSTL sisters (PLSTL1 and PLSTL2)
The mean of Papillon–Lefèvre syndrome toothed (PLST) probing pocket depth was 8.82 mm ( ± 3.46), which did not regress with previous regular periodontal treatment (Table 1)

Summary

Introduction

Papillon and Lefèvre first described the Papillon–Lefèvre syndrome (PLS) in 1924 (Papillon and Lefevre, 1924). PLS is a hereditary autosomal recessive and rare condition that affects one to four people per million (Hart and Shapira, 1994). Consanguineous marriages are PLS individuals’ origin (Bhavsar et al, 2013; Bullón et al, 2018). The main impact of consanguinity is the increased expression of multiple mutations encoding rare autosomal recessive genetic disorders, with an increased risk for first cousin couples to bear affected children. The periodontal condition and tooth loss generate high sensitivity in patients with PLS and poor diet quality (Hattab, 2019). These subjects present an increased incidence of skin and oral infections, which led to a substantial immunological disorder hypothesis at the first line of cellular defense. The immune system impairment may explain the predisposition to oral infection and periodontitis in PLS as a primary etiological component

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