Clinical, Microbiological and Immunological Effects of the Adjuvant Use of Systemic Antibiotics and Probiotics in the Non-surgical Treatment of Periodontitis

Clinical, Microbiological and Immunological Effects of the Adjuvant Use of Systemic Antibiotics and Probiotics in the Non-surgical Treatment of Periodontitis: a Controlled and Randomized Clinical Trial

Although robust evidence supports the benefits of antibiotics in periodontal treatment, the potential adverse effects of this therapy cannot be overlooked. These include concerns regarding the emergence of antimicrobial resistance and the non-ecological impact of antimicrobials on the gut microbiome, which may be closely linked to the etiopathogenesis of periodontitis and to the maintenance of long-term periodontal treatment outcomes. In this context, probiotics may represent a promising alternative strategy to reduce the need for antibiotics, particularly in severe cases of periodontitis.

Study Overview

• Status: Completed
• Conditions: Periodontal Disease; Healthy Adult Participants
• Intervention / Treatment: Other: Probiotic Therapy; Drug: Amoxicilin and Metronidazole

Detailed Description

Scaling and root planing (SRP) is the most widely used treatment modality in periodontal therapy. However, a subset of periodontal sites does not respond adequately to this approach, and certain individuals exhibit susceptibility patterns that limit their response to initial treatment. Therefore, to overcome the limitations of SRP alone, adjunctive therapies-such as antibiotics and probiotics-may be employed.

The aim of this randomized, controlled, double-blind clinical trial is to evaluate the effects of adjunctive therapies (antibiotics and probiotics) associated with non-surgical periodontal therapy in individuals diagnosed with periodontitis stages III or IV, grades B or C. A total of sixty individuals with a clinical diagnosis of periodontitis will be treated with SRP alone or SRP combined with antibiotics or probiotics. Participants will be randomly allocated into three groups: Control (SRP), Test 1 (SRP + amoxicillin and metronidazole), and Test 2 (SRP + probiotics).

The adjunctive agents evaluated in this study will be a combination of systemic antibiotics (amoxicillin and metronidazole) and the probiotic Bifidobacterium animalis subsp. lactis HN019. Antibiotics will be administered for 14 days, three times daily, whereas probiotics will be administered for 90 days, twice daily. Adjunctive therapies will commence immediately after the first week of periodontal instrumentation.

Clinical follow-up will be conducted at baseline (pre-intervention), and at 3, 6, 9, and 12 months post-treatment. At baseline, 6 months, and 12 months, gingival crevicular fluid, subgingival biofilm, peripheral blood, and fecal samples will be collected, along with the assessment of periodontal clinical parameters. Levels of the cytokines IL-6, TNF-α, IFN-γ, IL-10, IL-1β, and IL-8 will be quantified in gingival crevicular fluid and peripheral blood samples using enzyme-linked immunosorbent assays.

Subgingival biofilm and fecal samples will be subjected to 16S ribosomal RNA gene amplification by PCR and sequenced using Illumina technology (MiSeq or MiniSeq; Illumina, San Diego, CA, USA). Sequencing data will be analyzed using reference databases of the human oral and intestinal microbiomes. Statistical analyses will be performed using an alpha level of 0.05 (p < 0.05).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14040-904
      • Universidade de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults with a diagnosis of generalized periodontitis, defined as involvement of ≥30% of teeth, classified as: Stage III or Stage IV, and Grade B or Grade C, according to the 2018 classification.
• Presence of at least one tooth with ≥1 interproximal site exhibiting: Probing depth (PD) ≥6 mm, and Clinical attachment loss (CAL) ≥5 mm.
• Presence of at least 15 teeth, excluding third molars and teeth indicated for extraction.
• Presence of at least 6 non contiguous teeth, each with ≥1 interproximal site presenting PD and CAL ≥5 mm.

Exclusion Criteria:

• Current smokers or former smokers who quit less than 5 years prior to enrollment.
• Pregnant or breastfeeding women.
• History of periodontal treatment within the previous 6 months.
• Continuous use of oral antiseptics within the last 6 months.
• Use of systemic antibiotics, corticosteroids, non steroidal anti inflammatory drugs, immunosuppressants, estrogen, estrogen receptor modulators, or medications affecting bone metabolism (e.g., alendronate, calcitonin) within the last 6 months.
• Presence of systemic conditions that may alter the host response, including: Diabetes mellitus, HIV infection, Down syndrome.
• Medical conditions requiring antibiotic prophylaxis for dental procedures (e.g., mitral valve prolapse).
• Known allergy or hypersensitivity to amoxicillin, metronidazole, penicillins, or related compounds.
• Use of probiotics within the last 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Placebo
Experimental: Probiotic; To compare the effects of probiotic as an adjuvant therapy	Other: Probiotic Therapy; Patients will receive probiotic lozenges as an adjuvant therapy to periodontal treatment.
Experimental: Antibiotic; To compare the effects as an adjuvant therapy	Drug: Amoxicilin and Metronidazole; The antibiotic group will receive amoxicilin and metronidazole, the probiotic group will receive probiotics; Other Names: Amoxicilin, Metronidazole, Antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periodontal Probing Depth (PD)	A full-mouth periodontal examination will be performed using a North Carolina periodontal probe (Hu-Friedy, Chicago, IL, USA). Probing depth (PD) will be measured in millimeters at six sites per tooth.	every 3 months, up to 1 year
Clinical Attachment Level (CAL)	Clinical attachment level (CAL) will be measured in millimeters at six sites per tooth using a North Carolina periodontal probe.	Every 3 months, up to 1 year
Bleeding on Probing (BOP)	Bleeding on probing will be assessed dichotomously (presence/absence) at six sites per tooth during full-mouth periodontal examination	Every 3 months, up to 1 year
Visible Supragingival Biofilm	Presence or absence of visible supragingival biofilm will be assessed on four tooth surfaces during full-mouth periodontal examination.	Every 3 months, up to 1 year
Distance from Cementoenamel Junction to Gingival Margin	The distance from the cementoenamel junction to the gingival margin will be measured in millimeters at six sites per tooth.	Every 3 months, up to 1 year
Suppuration	Suppuration will be assessed dichotomously (presence/absence) at six sites per tooth during periodontal examination.	Every 3 months, up to 1 year

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Study Director: Michel Reis Messora, PhD, University of Sao Paulo

Publications and helpful links

General Publications

• Haas AN, Furlaneto F, Gaio EJ, Gomes SC, Palioto DB, Castilho RM, Sanz M, Messora MR. New tendencies in non-surgical periodontal therapy. Braz Oral Res. 2021 Sep 24;35(Supp 2):e095. doi: 10.1590/1807-3107bor-2021.vol35.0095. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2023
• Primary Completion (Actual): January 30, 2026
• Study Completion (Actual): February 11, 2026

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: probiotics; periodontitis; periodontal disease; antibiotics
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Periodontitis; Periodontal Diseases; Anti-Infective Agents; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Imidazoles; Nitroimidazoles; Nitro Compounds; Metronidazole; Anti-Bacterial Agents
• Other Study ID Numbers: 75898223.7.0000.5419

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol will be shared as a guide for further research.
• IPD Sharing Time Frame: After the publication of the study
• IPD Sharing Access Criteria: Open access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No