Toll-like receptor-4 activation by subgingival biofilm and periodontal treatment response

Ren Jie Jacob Chew; Yi Ling Tang; Xin Yi Sheena Lin; Feng Jun Bryan Oh; Ruiqi Paul Sim; Erica Jade Anwar; Philip M. Preshaw; Kai Soo Tan

doi:10.1007/s00784-023-04877-8

Toll-like receptor-4 activation by subgingival biofilm and periodontal treatment response

Ren Jie Jacob Chew, Yi Ling Tang, Xin Yi Sheena Lin, Feng Jun Bryan Oh, Ruiqi Paul Sim, Erica Jade Anwar, Philip M. Preshaw (Lead / Corresponding author), Kai Soo Tan (Lead / Corresponding author)

Dentistry

Research output: Contribution to journal › Article › peer-review

Abstract

Objectives: This study aims to investigate longitudinally the activation of Toll-like receptor-4 (TLR-4) by subgingival biofilm samples before and after nonsurgical periodontal therapy (NSPT).

Materials and methods: Forty periodontitis patients received NSPT and were reviewed 3 and 6 months post-treatment. Subgingival biofilm was sampled from 4 teeth per patient, at baseline and each follow-up time point. TLR-4 activation was determined using the HEK-BLUE™/hTLR4 system. Changes in TLR-4 activation and probing pocket depths (PPDs) were evaluated using generalised linear models, and the association between TLR-4 activation and pocket reduction (defined as 6-month PPDs ≤ 3mm) was determined using generalised estimating equations.

Results: At 6 months, the mean TLR-4 activation by subgingival biofilm samples was significantly reduced from 11.2AU (95%CI 7.1AU, 15.4AU) to 3.6AU (95%CI 2.3AU, 4.8AU, p < 0.001), paralleling significant reductions in mean PPDs at sampled sites. The response to NSPT was associated with longitudinal TLR-4 activation profiles, with significantly higher TLR-4 activation by subgingival biofilm obtained from sites that did not achieve pocket reduction, compared to sites at which pocket reduction was achieved.

Conclusions: The activation of TLR-4 by subgingival biofilm samples was reduced after NSPT, and this reduction was significantly associated with the clinical improvements (PPD reductions) at sampled sites. Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.

Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.

Original language	English
Number of pages	9
Journal	Clinical Oral Investigations
Early online date	31 Jan 2023
DOIs	https://doi.org/10.1007/s00784-023-04877-8
Publication status	E-pub ahead of print - 31 Jan 2023

Keywords

Biomarkers
Endotoxins
Lipopolysaccharides
Periodontal debridement
Periodontitis

ASJC Scopus subject areas

Dentistry(all)

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10.1007/s00784-023-04877-8

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title = "Toll-like receptor-4 activation by subgingival biofilm and periodontal treatment response",

abstract = "Objectives: This study aims to investigate longitudinally the activation of Toll-like receptor-4 (TLR-4) by subgingival biofilm samples before and after nonsurgical periodontal therapy (NSPT). Materials and methods: Forty periodontitis patients received NSPT and were reviewed 3 and 6 months post-treatment. Subgingival biofilm was sampled from 4 teeth per patient, at baseline and each follow-up time point. TLR-4 activation was determined using the HEK-BLUE{\texttrademark}/hTLR4 system. Changes in TLR-4 activation and probing pocket depths (PPDs) were evaluated using generalised linear models, and the association between TLR-4 activation and pocket reduction (defined as 6-month PPDs ≤ 3mm) was determined using generalised estimating equations. Results: At 6 months, the mean TLR-4 activation by subgingival biofilm samples was significantly reduced from 11.2AU (95%CI 7.1AU, 15.4AU) to 3.6AU (95%CI 2.3AU, 4.8AU, p < 0.001), paralleling significant reductions in mean PPDs at sampled sites. The response to NSPT was associated with longitudinal TLR-4 activation profiles, with significantly higher TLR-4 activation by subgingival biofilm obtained from sites that did not achieve pocket reduction, compared to sites at which pocket reduction was achieved. Conclusions: The activation of TLR-4 by subgingival biofilm samples was reduced after NSPT, and this reduction was significantly associated with the clinical improvements (PPD reductions) at sampled sites. Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.",

keywords = "Biomarkers, Endotoxins, Lipopolysaccharides, Periodontal debridement, Periodontitis",

author = "Chew, {Ren Jie Jacob} and Tang, {Yi Ling} and Lin, {Xin Yi Sheena} and Oh, {Feng Jun Bryan} and Sim, {Ruiqi Paul} and Anwar, {Erica Jade} and Preshaw, {Philip M.} and Tan, {Kai Soo}",

note = "Funding Information: This study was supported by postgraduate research grants from the Faculty of Dentistry, National University of Singapore, Singapore. Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2023",

month = jan,

day = "31",

doi = "10.1007/s00784-023-04877-8",

language = "English",

journal = "Clinical Oral Investigations",

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AU - Chew, Ren Jie Jacob

AU - Tang, Yi Ling

AU - Lin, Xin Yi Sheena

AU - Oh, Feng Jun Bryan

AU - Sim, Ruiqi Paul

AU - Anwar, Erica Jade

AU - Preshaw, Philip M.

AU - Tan, Kai Soo

N1 - Funding Information: This study was supported by postgraduate research grants from the Faculty of Dentistry, National University of Singapore, Singapore. Copyright: © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2023/1/31

Y1 - 2023/1/31

N2 - Objectives: This study aims to investigate longitudinally the activation of Toll-like receptor-4 (TLR-4) by subgingival biofilm samples before and after nonsurgical periodontal therapy (NSPT). Materials and methods: Forty periodontitis patients received NSPT and were reviewed 3 and 6 months post-treatment. Subgingival biofilm was sampled from 4 teeth per patient, at baseline and each follow-up time point. TLR-4 activation was determined using the HEK-BLUE™/hTLR4 system. Changes in TLR-4 activation and probing pocket depths (PPDs) were evaluated using generalised linear models, and the association between TLR-4 activation and pocket reduction (defined as 6-month PPDs ≤ 3mm) was determined using generalised estimating equations. Results: At 6 months, the mean TLR-4 activation by subgingival biofilm samples was significantly reduced from 11.2AU (95%CI 7.1AU, 15.4AU) to 3.6AU (95%CI 2.3AU, 4.8AU, p < 0.001), paralleling significant reductions in mean PPDs at sampled sites. The response to NSPT was associated with longitudinal TLR-4 activation profiles, with significantly higher TLR-4 activation by subgingival biofilm obtained from sites that did not achieve pocket reduction, compared to sites at which pocket reduction was achieved. Conclusions: The activation of TLR-4 by subgingival biofilm samples was reduced after NSPT, and this reduction was significantly associated with the clinical improvements (PPD reductions) at sampled sites. Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.

AB - Objectives: This study aims to investigate longitudinally the activation of Toll-like receptor-4 (TLR-4) by subgingival biofilm samples before and after nonsurgical periodontal therapy (NSPT). Materials and methods: Forty periodontitis patients received NSPT and were reviewed 3 and 6 months post-treatment. Subgingival biofilm was sampled from 4 teeth per patient, at baseline and each follow-up time point. TLR-4 activation was determined using the HEK-BLUE™/hTLR4 system. Changes in TLR-4 activation and probing pocket depths (PPDs) were evaluated using generalised linear models, and the association between TLR-4 activation and pocket reduction (defined as 6-month PPDs ≤ 3mm) was determined using generalised estimating equations. Results: At 6 months, the mean TLR-4 activation by subgingival biofilm samples was significantly reduced from 11.2AU (95%CI 7.1AU, 15.4AU) to 3.6AU (95%CI 2.3AU, 4.8AU, p < 0.001), paralleling significant reductions in mean PPDs at sampled sites. The response to NSPT was associated with longitudinal TLR-4 activation profiles, with significantly higher TLR-4 activation by subgingival biofilm obtained from sites that did not achieve pocket reduction, compared to sites at which pocket reduction was achieved. Conclusions: The activation of TLR-4 by subgingival biofilm samples was reduced after NSPT, and this reduction was significantly associated with the clinical improvements (PPD reductions) at sampled sites. Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.Clinical relevance: This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.

KW - Biomarkers

KW - Endotoxins

KW - Lipopolysaccharides

KW - Periodontal debridement

KW - Periodontitis

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JO - Clinical Oral Investigations

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ER -

Toll-like receptor-4 activation by subgingival biofilm and periodontal treatment response

Abstract

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