The purpose of this study is to characterize the effect of minocycline microspheres (MM) administered as an adjunct to scaling and rooting planning (SRP) on the subgingival community composition and metatranscriptome functional profile, in comparison to a group treated with SRP only and to periodontally-healthy subjects.

Patients attending the West Virginia University School of Dentistry Clinics will be invited to participate in this study. Thirty periodontitis patients (stage II, III or IV) with ≥4 teeth with a probing pocket depth (PPD) >4 mm; at least 1 tooth with a PPD >6 mm and clinical attachment loss (CAL) ≥2 mm, and radiographic evidence of bone loss will be recruited.

Clinical examination will include measurement of clinical attachment loss (CAL), probing pocket depth (PPD), bleeding on probing (BOP), and plaque score (PS) at 6 sites per tooth. Furcation involvement (FI) will also be recorded. Radiographic examination will include full-mouth radiographic series. Patients will receive a clinical examination at baseline (V1, before periodontal therapy), and their subgingival plaque biofilms will be sampled at a second visit (V2) two weeks after this initial exam to collect subgingival plaque not disrupted by the examination procedures.

Subjects will be then randomized to one of two groups: SRP only and SRP + MM. Periodontal therapy will consist of one visit (V3) full-mouth SRP alone or in combination with MM placed at all sites regardless of PPD. Each site will receive 1mg of MM for a total of 6mg of MM per tooth. In this manner we will also evaluate whether MM modifies the microbiome of shallow sites, since subgingival microbiome dysbiosis affects shallow sites of subjects with periodontitis and therefore represents a risk for future disease progression.

Subjects will be evaluated 2 months after receiving periodontal therapy (V4). At this visit subgingival plaque samples will be collected and clinical outcomes evaluated. Clinical examinations and plaque collection will be conducted by one calibrated examiner.

Fifteen periodontally-healthy subjects will also be recruited from the West Virginia University School of Dentistry Clinics. Subjects will receive a clinical examination and their subgingival communities sampled at the same visit (V1).

Inclusion Criteria for randomized participants:

• Have at least 20 natural teeth with a diagnosis of Periodontitis (stage II, III, or IV).

Inclusion Criteria for periodontally-healthy participants:

• Diagnosis of healthy periodontium defined as ≤9% of sites bleeding on probing with absence of interproximal attachment loss and bone loss

Exclusion Criteria for all participants:

• Pregnancy or lactation
• Patients with diabetes mellitus or any other systemic disease that can modify periodontitis
• Current smokers
• Current use of f any medication with known effects on periodontitis
• Use of non-steroidal anti-inflammatory drugs
• Use of local or systemic antibiotics within the last 3 months
• Subjects with conditions requiring prophylactic antibiotics
• Subjects allergic to any of the tetracyclines
• Professional dental cleaning within the last 3 months
• SRP or surgical periodontal therapy in the previous year