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Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis

Scher, Jose U; Ubeda, Carles; Equinda, Michele; Khanin, Raya; Buischi, Yvonne; Viale, Agnes; Lipuma, Lauren; Attur, Mukundan; Pillinger, Michael H; Weissmann, Gerald; Littman, Dan R; Pamer, Eric G; Bretz, Walter A; Abramson, Steven B
OBJECTIVE.: To profile the subgingival oral microbiota abundance and diversity in never-treated, new-onset rheumatoid arthritis (NORA) patients. METHODS.: Periodontal disease (PD) status, clinical activity and sociodemographic factors were determined in patients with NORA, chronic RA (CRA) and healthy subjects. Massively parallel pyrosequencing was used to compare the composition of subgingival microbiota and establish correlations between presence/abundance of bacteria and disease phenotypes. Anti-P. gingivalis antibodies were tested to assess prior exposure. RESULTS.: The more advanced forms of periodontitis are already present at disease onset in NORA patients. The subgingival microbiota of NORA is distinct from controls. In most cases, however, these differences can be attributed to PD severity and are not inherent to RA. The presence and abundance of P. gingivalis is directly associated with PD severity as well, is not unique to RA, and does not correlate with anti-citrullinated peptide antibody (ACPA) titers. Overall exposure to P. gingivalis is similar in RA and controls, observed in 78.4% and 83.3%, respectively. Anaeroglobus geminatus correlated with ACPA/RF presence. Prevotella and Leptotrichia species are the only characteristic taxa in the NORA group irrespective of PD status. CONCLUSIONS.: NORA patients exhibit a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The subgingival microbiota of NORA patients is similar to CRA and healthy subjects of comparable PD severity. Although colonization with P. gingivalis correlates with PD severity, overall exposure is similar among groups. The role of A. geminatus and Prevotella/Leptotrichia species in this process merits further study.
PMCID:3428472
PMID: 22576262
ISSN: 0004-3591
CID: 178156

Response from professor bretz [Letter]

Bretz, Walter A
ORIGINAL:0011654
ISSN: 1532-3382
CID: 2368482

Low-dose doxycycline plus additional therapies may lower systemic inflammation in postmenopausal women with periodontitis [Comment]

Bretz, Walter A
SUBJECTS: Enrollment and study protocols took place between June 2002 and October 2005. This study was a supplemental project of a larger trial of cohorts recruited from university settings in Lincoln, Nebraska, and Stony Brook, New York. Female postmenopausal participants who had osteopenia and a history of moderate to advanced chronic periodontitis comprised the test group (n = 51; at baseline, n = 63) and placebo group (n = 62; at baseline, n = 64) after a 2-year study period. KEY EXPOSURE/STUDY FACTOR: Participants were allocated to a test group or a placebo group. Participants who belonged to the test group received subantimicrobial-dose-doxycycline (SDD)(20 mg of doxycycline hyclate) twice daily for 2 years. Participants in the control group received a look-alike placebo twice a day for 2 years. In addition, all patients received periodontal maintenance (every 3-4 months for the duration of the study) and were provided with a supply to be taken twice daily for the duration of the study of calcium (1200 mg) and vitamin D (400 IU). MAIN OUTCOME MEASURE: Markers of systemic inflammation (hs-CRP, myeloperoxidase, MMP-8, TIMP-1, MMP-9, MMP-2, IL-6, TNF-alpha, and IL-1beta) and lipid profiles (total cholesterol, HDL, LDL and VLDL cholesterol, and triglycerides). MAIN RESULTS: The combined treatment modalities (SDD + periodontal maintenance + dietary supplement) reduced hs-CRP levels as expressed by ratio of medians (SDD/placebo) by 18% compared with placebo (periodontal maintenance + dietary supplement) (0.82; confidence interval [CI] = 0.700.97; P = .02) after the 2-year study period when adjusting for the use of concomitant medications (statin, diuretics, aspirin). The combined treatment modalities significantly reduced MMP-9 (mean scanning units of treatment minus placebo) relative to placebo over the 2-year protocol (-28.44; CI = -40.17 to -16.72, P < .001). There were no statistically significant differences of lipid profiles between the combined treatment modalities and placebo group after a 2-year protocol. CONCLUSIONS: SDD when used as an adjunctive to periodontal maintenance plus dietary supplement significantly lowers serum biomarkers of inflammation in postmenopausal women with history of periodontitis.
PMID: 23253834
ISSN: 1532-3382
CID: 377032

The inhibitory activity of typified propolis against Enterococcus species

Moncla, Bernard J; Guevara, Peter W; Wallace, James A; Marcucci, Maria C; Nor, Jacques E; Bretz, Walter A
Propolis, a natural bee product widely used for its antimicrobial activity, was tested against isolates of Enterococcus from humans, pig-tailed macaques, isolates of refractory endodontic treatment cases, and isolates from Lactobacillus-containing food supplements. Typification of the propolis was performed by high-performance liquid chromatography (HPLC) by which prenylated compounds, cinnamic acid derivatives, and flavonoids were detected as the main constituents. Minimum inhibitory concentrations (MIC) were determined using the agar dilution method. All human and animal Enterococcus isolates demonstrated MIC values of 1600 microg/mL. Enterococcal species of human and animal origin were inhibited by propolis. Particularly, human isolates of E. faecium and E. faecalis of refractory endodontic treatment cases were susceptible to propolis of Brazilian origin.
PMID: 22888529
ISSN: 0939-5075
CID: 178155

Rheumatoid arthritis and periodontitis: A possible link via "citation"

Rosenstein ED; Scher JU; Bretz WA; Weissmann G
PMID: 22019980
ISSN: 1095-8274
CID: 143404

Environmental and genetic contributions to indicators of oral malodor in twins

Bretz, Walter A; Biesbrock, Aaron; Corby, Patricia M; Corby, Andrea L; Bretz, Walter G; Wessel, Jennifer; Schork, Nicholas J
This study aimed to: (1) determine concordance rates of self-reported and subjectively determined indicators of oral malodor in twins; (2) determine the relative contributions of genetic and environmental factors to levels of volatile sulfur compounds (VSCs) in intraoral and exhaled breath. Fifty-one twin pairs participated in the study. Measurements of VSCs were obtained by a halimeter. The presence of tongue coatings was determined and twins filled out a 32-item questionnaire on oral malodor indicators independently of one another. Estimates of heritability (h2) for halimeter measurements were computed by SOLAR. The concordance rates for the presence of tongue coating among identical and fraternal twins were 67% and 11%, respectively. In the 10 most informative items, 70% exhibited higher concordance rates for identical than for fraternal twins. Of particular interest were the differences in concordance rates for dry mouth, sinus infection and unusual sweating. The h2 for intraoral breath was 0.28 +/- 0.17 (NS), whereas the h2 for exhaled breath was 0.50 +/- 0.20 (p = .0207). The concordance rates of tongue coatings and malodor indicators were higher in identical twins than in fraternal twins. Intraoral breath VSC values were primarily attributable to environmental factors, whereas exhaled breath VSC values were partially explained by genetic factors.
PMCID:3335767
PMID: 22506313
ISSN: 1832-4274
CID: 167104

Low-Dose Doxycycline Plus Additional Therapies may Lower Systemic Inflammation in Postmenopausal Women with Periodontitis

Bretz, Walter A
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial. Payne JB, Golub LM, Stoner JA, Lee H-M, Reinhardt RA, Sorsa T, Slepian MJ. J Am Dent Assoc 2011;142;262-73. REVIEWER: Walter A. Bretz, DDS, PhD PURPOSE/QUESTION: To determine whether long-term subantimicrobial-dose-doxycycline (SDD) periodontal therapy could reduce serum biomarkers of systemic inflammation and improve lipid profiles in postmenopausal women who have systemic osteopenia and chronic periodontitis SOURCE OF FUNDING: NIH/NIDCR grant R01DE012872. TYPE OF STUDY/DESIGN: Randomized controlled trial LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable
PMID: 22078832
ISSN: 1532-3390
CID: 155427

Re: Clinical periodontal and microbiologic parameters in patients with rheumatoid arthritis [Letter]

Rosenstein, Elliot D; Scher, Jose U; Bretz, Walter A; Weissmann, Gerald
PMID: 22043938
ISSN: 0022-3492
CID: 156357

Emerging technologies for the prevention of dental caries. Are current methods of prevention sufficient for the high risk patient?

Bretz, Walter A; Rosa, Odila P S
Fluorides and chlorhexidine are technologies that are 65 and 40 years old, respectively. This overview argues that current methods of caries prevention are not effective for the high caries risk patient. In this review examples, arguments and recommendations are provided to address the high caries risk patient that include: failure of comprehensive chemical modalities treatments to address the high caries risk patient; ecological alteration - would this be an effective approach?; and biomaterials and oral microbiome research to address the high caries risk patient
PMCID:3205412
PMID: 21726223
ISSN: 0020-6539
CID: 155414

Dental caries pathogenicity: a genomic and metagenomic perspective

Peterson, Scott N; Snesrud, Erik; Schork, Nicholas J; Bretz, Walter A
In this review we address the subject of dental caries pathogenicity from a genomic and metagenomic perspective. The application of genomic technologies is certain to yield novel insights into the relationship between the bacterial flora, dental health and disease. Three primary attributes of bacterial species are thought to have direct impact on caries development, these include: adherence on tooth surfaces (biofilm formation), acid production and acid tolerance. Attempts to define the specific aetiological agents of dental caries have proven to be elusive, supporting the notion that caries aetiology is perhaps complex and multi-faceted. The recently introduced Human Microbiome Project (HMP) that endeavors to characterise the micro-organisms living in and on the human body is likely to shed new light on these questions and improve our understanding of polymicrobial disease, microbial ecology in the oral cavity and provide new avenues for therapeutic and molecular diagnostics developments
PMCID:3699854
PMID: 21726221
ISSN: 0020-6539
CID: 155443