Multi-species oral biofilm promotes reconstructed human gingiva epithelial barrier function

• Published in: Scientific reports Vol. 8; no. 1; pp. 16061 - 12
• Main Authors: Shang, Lin, Deng, Dongmei, Buskermolen, Jeroen Kees, Janus, Marleen Marga, Krom, Bastiaan Philip, Roffel, Sanne, Waaijman, Taco, van Loveren, Cor, Crielaard, Wim, Gibbs, Susan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-10-2018; Nature Publishing Group
• Subjects: 13; 13/106; 13/107; 13/21; 13/51; 14; 14/32; 38; 38/90; 631/326/88; 631/443; 631/80; Adrenomedullin; Biofilms; CCL20 protein; Epithelium; Gingiva; Humanities and Social Sciences; Hydrogels; Inflammation; Interleukin 6; Lamina propria; Microbiomes; Microbiota; Microorganisms; Mucosa; Mucous membrane; multidisciplinary; Saliva; Science; Science (multidisciplinary); Species; Adrenomedullin (ADM); Biofilm Exposure; Elafin; Host-microbiome Interactions; Human Gingiva
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-34390-y

Since the oral mucosa is continuously exposed to abundant microbes, one of its most important defense features is a highly proliferative, thick, stratified epithelium. The cellular mechanisms responsible for this are still unknown. The aim of this study was to determine whether multi-species oral biofilm contribute to the extensive stratification and primed antimicrobial defense in epithelium. Two
in vitro
models were used: 3D reconstructed human gingiva (RHG) and oral bacteria representative of multi-species commensal biofilm. The organotypic RHG consists of a reconstructed stratified gingiva epithelium on a gingiva fibroblast populated hydrogel (lamina propria). Biofilm was cultured from healthy human saliva, and consists of typical commensal genera
Granulicatella
and major oral microbiota genera
Veillonella
and
Streptococcus
. Biofilm was applied topically to RHG and host–microbiome interactions were studied over 7 days. Compared to unexposed RHG, biofilm exposed RHG showed increased epithelial thickness, more organized stratification and increased keratinocyte proliferation. Furthermore biofilm exposure increased production of RHG anti-microbial proteins Elafin, HBD2 and HBD3 but not HBD1, adrenomedullin or cathelicidin LL-37. Inflammatory and antimicrobial cytokine secretion (IL-6, CXCL8, CXCL1, CCL20) showed an immediate and sustained increase. In conclusion, exposure of RHG to commensal oral biofilm actively contributes to RHG epithelial barrier function.