Antimicrobial-induced oral dysbiosis exacerbates naturally occurring alveolar bone loss

被引：6

作者：

Swanson, Brooks A. ^{[1
,2
,3
]}

Carson, Matthew D. ^{[1
,2
,3
]}

Hathaway-Schrader, Jessica D. ^{[1
,2
,3
]}

Warner, Amy J. ^{[1
,2
,3
]}

Kirkpatrick, Joy E. ^{[1
,2
,3
,4
]}

Corker, Alexa ^{[1
,2
,3
]}

Alekseyenko, Alexander, V ^{[1
,5
,6
]}

Westwater, Caroline ^{[1
,7
]}

Aguirre, J. Ignacio ^{[8
]}

Novince, Chad M. ^{[1
,2
,3
]}

机构：

[1] Med Univ South Carolina, Coll Dent Med, Dept Oral Hlth Sci, Charleston, SC 29425 USA

[2] Med Univ South Carolina, Coll Dent Med, Dept Stomatol, Div Periodont, Charleston, SC 29425 USA

[3] Med Univ South Carolina, Coll Med, Dept Pediat, Div Endocrinol, Charleston, SC 29425 USA

[4] Med Univ South Carolina, Coll Pharm, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA

[5] Med Univ South Carolina, Program Human Microbiome Res, Biomed Informat Ctr, Dept Publ Hlth Sci,Coll Med, Charleston, SC 29425 USA

[6] Med Univ South Carolina, Coll Hlth Profess, Dept Healthcare Leadership & Management, Charleston, SC 29425 USA

[7] Med Univ South Carolina, Hollings Canc Ctr, Dept Microbiol & Immunol, Charleston, SC 29425 USA

[8] Univ Florida, Coll Vet Med, Dept Physiol Sci, Gainesville, FL 32610 USA

来源：

FASEB JOURNAL | 2021年 / 35卷 / 11期

关键词：

alveolar bone loss; antibiotics; antiseptics; host microbial interactions; microbiota; EXPERIMENTAL PERIODONTAL-DISEASE; HISTOLOGICAL-CHANGES; CRITICAL WINDOWS; GENE-EXPRESSION; ANTIBIOTICS; IMMUNE; CELLS; NEUTROPHILS; MICROBIOTA; THERAPY;

D O I：

10.1096/fj.202101169R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline- versus vehicle-treated germ-free mice had similar alveolar bone loss outcomes, implying that antimicrobial-driven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring alveolar bone loss in SPF mice. Chlorhexidine further disrupted the oral bacteriome and worsened alveolar bone loss in minocycline-treated SPF mice, validating that antimicrobial-induced oral dysbiosis has deleterious effects on alveolar bone. Minocycline enhanced osteoclast size and interface with alveolar bone in SPF mice. Neutrophils and plasmacytoid dendritic cells were upregulated in cervical lymph nodes of minocycline-treated SPF mice. Paralleling the upregulated proinflammatory innate immune cells, minocycline therapy increased T(H)1 and T(H)17 cells that have known pro-osteoclastic actions in the alveolar bone. This report reveals that antimicrobial perturbation of the commensal microbiota induces a proinflammatory oral dysbiotic state that exacerbates naturally occurring alveolar bone loss.

引用

页数：20

共 88 条

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