Effects of combined probiotics and antibiotics administration in impacted third molar surgery: a randomized controlled trial

Introduction

The surgical removal of impacted third molars is among the most prevalent procedures performed in oral surgery and is frequently associated with postoperative complications such as pain, swelling, and infection (1). To mitigate these risks, systemic antibiotics—most commonly Amoxicillin or Amoxicillin/Clavulanic Acid—are extensively employed. Although generally effective in preventing infections, these antibiotics are also associated with a high incidence of adverse effects, notably gastrointestinal disturbances, and contribute significantly to the development of antimicrobial resistance (2,3).

The rising concern regarding inappropriate antibiotic prescribing within the field of dentistry has emphasized the necessity for more targeted and evidence-based therapeutic approaches (4,5). In fact, the frequency of unnecessary prescriptions remains elevated, and the employment of antibiotics in healthy individuals undergoing uncomplicated extractions has been critically scrutinized (6).

Antibiotic-induced dysbiosis, characterized by an imbalance in the intestinal microbiota, is a common and often under appreciated adverse effect, manifesting as symptoms such as nausea, diarrhea, and urogenital infections (7,8). Probiotics—defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host”—have emerged as a potential adjunctive therapy aimed at maintaining microbiota stability and enhancing patient tolerance to antibiotics (9). Among the probiotic strains examined, Bifidobacterium breve PRL2020 has demonstrated promising features, including resilience to antibiotic co-administration and the ability to sustain a stable microbial equilibrium within the gut (10,11). Preliminary evidence indicates that probiotic supplementation may mitigate postoperative pain and inflammation associated with oral surgery, although existing data remain limited and heterogeneous (12,13). This randomized controlled pilot study was conducted to evaluate the effects of co-administering B. breve PRL2020 alongside standard antibiotic therapy in patients undergoing surgical extraction of impacted third molars. It is hypothesized that this combination will reduce the incidence of antibiotic-associated gastrointestinal and urogenital side effects, improve treatment tolerability, and promote overall recovery. Initial results support these hypotheses, underscoring the potential role of integrated therapeutic protocols in oral surgical care.

Materials and Methods

This study was designed as a single-center, randomized, controlled pilot clinical trial to assess the effects of combined probiotic and antibiotic therapy on postoperative tolerance in patients undergoing surgical extraction of impacted third molars. The study adhered to the principles of the Declaration of Helsinki and received approval from the local ethics committee. Written informed consent was obtained from all participants before enrollment. A total of 42 adult patients (≥18 years), referred for the extraction of at least one impacted third molar, were recruited between [insert dates]. Inclusion criteria were good general health, clinical indication for surgical third molar extraction due to impaction or associated pathology, and the absence of systemic diseases. Exclusion criteria included recent antibiotic use (within 30 days), gastrointestinal disorders, immunodeficiency, pregnancy or breastfeeding, and known allergy or intolerance to any study medication (antibiotics or probiotics).

Following initial screening and obtaining informed consent, patients were randomly allocated into one of four treatment groups using a computerized randomization tool, with an allocation ratio of 1:1:1:1.

1. Group A – Amoxicillin 1,000 mg every 12 hours for 6 days.
2. Group B – Amoxicillin 875 mg + Clavulanic Acid 125 mg every 12 hours for 6 days.
3. Group C – Same regimen as Group A, plus Bifidobacterium breve PRL2020 (0.8 g oral stick, once daily) for 6 days.
4. Group D – Same regimen as Group B, plus Bifidobacterium breve PRL2020 (0.8 g oral stick, once daily) for 6 days.

The probiotic formulation, supplied by PharmExtracta, comprised a standardized dose of Bifidobacterium breve PRL2020, presented in powdered form within single-dose oral sticks. Participants were advised to dissolve the powder in water and ingest it thirty minutes prior to breakfast.

All surgical procedures were conducted by the same skilled oral surgeon employing a standardized protocol, which included local anesthesia with articaine 4% containing epinephrine 1:100,000, elevation of a full-thickness mucoperiosteal flap, removal of bone as necessary, tooth sectioning, and primary closure utilizing resorbable sutures.

Clinical and subjective data were collected at three designated time points utilizing structured questionnaires.

• T0 (preoperative): demographic data, medical history, and preoperative anxiety.
• T1 (14 days postoperative): incidence of adverse effects (gastrointestinal, urogenital, systemic),adherence to therapy, and pain perception (Visual Analog Scale).
• T2 (2 months postoperative): presence of late complications and patient-reported quality of recovery.

Patients who did not complete all scheduled follow-ups or questionnaires were excluded from the final analysis. Ultimately, a total of 32 participants, with 8 in each group, were incorporated into the statistical evaluation. The data were analyzed utilizing SPSS software (version X.X, IBM Corp., Armonk, NY, USA). Continuous variables are presented as mean ± standard deviation. Comparisons between two groups were conducted using Student’s t-test, while one-way ANOVA was employed for comparisons among multiple groups. A p-value of less than 0.05 was deemed to be statistically significant.

Results

Out of the 42 patients enrolled, 32 successfully completed all phases of the study and were consequently included in the final analysis. The participants were evenly allocated across the four treatment groups. At the 14-day follow-up, a distinct difference was observed between the groups receiving antibiotics alone and those administered combined probiotic-antibiotic therapy (Fig. 1).

Gastrointestinal symptoms, including nausea, diarrhea, abdominal pain, and vomiting, were frequently reported among patients receiving only antibiotics. Conversely, these symptoms occurred significantly less often in patients who received the combined regimen. Notably, there were no reports of vomiting within the probiotic groups, and only mild and transient gastrointestinal discomfort was observed in a small subset of patients. Urogenital complications, such as candidiasis and cystitis, were observed solely in the groups receiving antibiotics and were not present in those supplemented with probiotics. Fatigue was consistently reported across all four groups, with no statistically significant variations, indicating a non-specific or multifactorial etiology.

By the two-month follow-up, the majority of symptoms had resolved in all groups. However, patients in the antibiotic-only groups continued to report a higher incidence of residual gastrointestinal or urogenital disturbances than those who received probiotics (Fig. 2)

Overall, the results indicate that the addition of Bifidobacterium breve PRL2020 to standard antibiotic therapy enhances treatment tolerability and mitigates adverse effects, especially those related to the gastrointestinal and urogenital systems. These findings substantiate the hypothesis that probiotic co-administration provides clinical benefits in the postoperative management of third molar surgery.

Discussion

The findings of this study indicate that the incorporation of probiotics, notably Bifidobacterium breve PRL2020, into conventional antibiotic protocols can markedly diminish gastrointestinal and urogenital adverse effects subsequent to the surgical removal of impacted third molars. These outcomes are consistent with prior reports demonstrating that probiotics alleviate antibiotic-induced dysbiosis and enhance patient tolerance during pharmacological interventions (14,15). The observed reduction in gastrointestinal disturbances supports the hypothesis that probiotics contribute to maintaining the integrity and balance of the intestinal microbiota, even during concurrent antibiotic therapy (16,17). Moreover, the absence of urogenital symptoms in the probiotic groups may indicate a systemic stabilizing effect of microbiota homeostasis. However, further microbiological and mechanistic studies are required to substantiate this claim (18,19). Interestingly, the comparable incidence of fatigue across all groups suggests that this symptom may be unrelated to microbiota alterations or treatment protocols, potentially reflecting a nonspecific postoperative response. Different surgical abilities of the operator and techniques may affect the patient’s response due to tissue exposure time during the procedures, which could influence the post-interventional recovery and symptoms (20,21,22).

These results align with recent research conducted by Di Pierro et al. (10), which established the safety and efficacy of B. breve PRL2020 in maintaining gut homeostasis during antibiotic therapy. However, although the findings are promising, they must be interpreted within the context of several limitations. The limited sample size hampers the ability to generalize the results, and the lack of microbiota sequencing constrains the capacity to directly associate clinical outcomes with microbial alterations.

Nonetheless, this study offers significant preliminary evidence endorsing targeted probiotic strains as a supplementary approach in oral surgical care, especially for patients at elevated risk of dysbiosis or antibiotic intolerance.

Conclusions

The concurrent administration of Bifidobacterium breve PRL2020 alongside standard antibiotic therapy in patients undergoing surgical extraction of impacted third molars has markedly decreased the occurrence of gastrointestinal and urogenital adverse effects, thereby improving overall treatment tolerability.

These findings suggest that probiotics may serve as a beneficial adjunct to antibiotic regimens in oral surgery, particularly for patients with a history of antibiotic sensitivity or dysbiosis. Although the sample size was limited, the results support the need for further large-scale, long-term research incorporating microbiological analysis to corroborate and expand upon these observations.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.