title: Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis.
abstract: Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the periodontal biofilm. Promoters of active resolution of inflammation, including resolvin E1 (RvE1), effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes. Two clinically relevant experiments were performed in rats: prevention and treatment of ligature-induced periodontitis with RvE1 topical treatment. The gingival transcriptome was evaluated by RNA sequencing of mRNA. The composition of the subgingival microbiota was characterized by 16S rDNA sequencing. Periodontitis was assessed by bone morphometric measurements and histomorphometry of block sections. H&E and tartrate-resistant acid phosphatase staining were used to characterize and quantify inflammatory changes. RvE1 treatment prevented bone loss in ligature-induced periodontitis. Osteoclast density and inflammatory cell infiltration in the RvE1 groups were lower than those in the placebo group. RvE1 treatment reduced expression of inflammation-related genes, returning the expression profile to one more similar to health. Treatment of established periodontitis with RvE1 reversed bone loss, reversed inflammatory gene expression, and reduced osteoclast density. Assessment of the rat subgingival microbiota after RvE1 treatment revealed marked changes in both prevention and treatment experiments. The data suggest that modulation of local inflammation has a major role in shaping the composition of the subgingival microbiota.
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and.
authors.forename: Chun-Teh
authors.identifier: 0000-0001-7812-5637
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Teles
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and.
authors.forename: Alpdogan
authors.identifier: 0000-0002-2679-9100
authors.initials: A
authors.lastname: Kantarci
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142.
authors.forename: Tsute
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142.
authors.forename: Jon
authors.initials: J
authors.lastname: McCafferty
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and.
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Starr
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and.
authors.forename: Luciana Carla Neves
authors.initials: LC
authors.lastname: Brito
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142.
authors.forename: Bruce J
authors.identifier: 0000-0002-5872-1906
authors.initials: BJ
authors.lastname: Paster
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and tvandyke@forsyth.org.
authors.forename: Thomas E
authors.identifier: 0000-0003-0568-124X
authors.initials: TE
authors.lastname: Van Dyke
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000188:drug therapy*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D010518:Periodontitis / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid