Review of probiotic use in Otolaryngology

Abstract

Objective

Probiotics have garnered considerable attention as an intervention for various conditions common to otolaryngology. The purpose of this review is to evaluate the current literature to offer recommendations about the safety and efficacy of probiotic management in otolaryngologic conditions.

Study Design

Narrative review.

Methods

PubMed and Google Scholar were queried using pertinent keywords to retrieve relevant studies with particular focus in the recent 5 years. All abstracts were assessed and studies, reviews and meta-analyses achieving evaluation of probiotic therapies or characterization of microbiome changes were included for further review. Studies were categorized by condition or anatomic region across various subspecialties. Key data parameters were extracted and evaluated across studies and treatment types.

Results

Strong evidence exists for the use probiotic agents to improve symptoms for allergic rhinitis, chronic rhinosinusitis and certain dental conditions. Despite promising results, further investigation is needed to evaluate and optimize probiotic delivery for mitigating otitis media, oropharyngeal inflammation and upper respiratory tract infections. Preclinical studies suggest that probiotics may potentially offer benefit for voice prosthesis maintenance, wound healing and mitigation of oral dysplasia.

Conclusion

Probiotic therapies may offer clinical benefit in a variety of contexts within the field of otolaryngology, especially for short-term relief of certain inflammatory conditions of the oral cavity, auditory and nasal cavities. Further investigation is warranted for evaluation of long-term outcomes and pathogenic deterrence.

INTRODUCTION

Technological and computational advances in metagenetic whole-genome shotgun sequencing have elucidated a dynamic biomolecular interplay between microbial communities and host pathways, contributing to a wide array of molecular processes, protective and pathophysiologic.^1,2 Key to these revelations is characterizing how commensal flora affect immune function, mediated in part by metabolic by-products and secreted molecules.^3,4

As defined by the World Health Organization, probiotics are live microorganisms administered to confer a health benefit when delivered in adequate amounts.⁵ In Otolaryngology, in vitro and murine studies inform clinical investigations of probiotic capsules, lozenges, and sprays for various conditions. Furthermore, some probiotics may potentiate wound healing or decrease the risk of perioperative infection, a complication that appears to be growing in head and neck procedures.⁶ Various mechanisms of probiotic benefit have been proposed including the secretion of bacteriocins and metabolic byproducts that modulate host inflammatory pathways. Probiotic effects may vary by strain, agent, formulation or delivery method and duration or course of treatment. It is not well-elucidated which conditions and products are optimal for clinical relief or benefit. The purpose of this review is to evaluate the existing body of literature in order to offer recommendations about the safety and efficacy of probiotic agents for the management of otolaryngologic conditions.

METHODS

PubMed and Google Scholar were queried using pertinent keywords to retrieve relevant studies ranging from preclinical trials to randomized control trials, crossover studies and also systematic reviews and meta-analyses. Studies were reviewed and differences in clinical outcomes or changes in microbiome profiling were investigated between study cohorts. Comparisons of probiotic formulations and delivery methods were considered across studies. All research articles were imported into Covidence (Melbourne, Australia) for data extraction and organization. Studies were prioritized by strength of evidence as well as recency, with a focus on studies reported in the past 5 years.

DISCUSSION

Otologic

Acute Otitis Media

About 80% of children experience acute otitis media (AOM).⁷ Probiotic remedies may offer an alternative to antibiotics, and various methods of delivery have been studied. A 2019 Cochrane review and meta-analysis of 17 randomized control trials (RCTs) by Scott et al. reported that probiotic usage reduced the incidence of AOM and was more pronounced with Lactobacillus products, compared to Streptococcus ones. The effect, however, did not extend to children prone to AOM (experiencing recurrent episodes).⁸ Among these, Cohen et al. reported that probiotic formula supplemented with Streptococcus and Lactobacillus did not improve AOM incidence (over 1 year) in otitis-prone infants.⁹ Nasal spray remedies, however, appeared to produce more consistent clinical benefit in the form of an alpha-streptococci strain that Roos et al. reported clinical benefit in 22 children compared to 12 controls.¹⁰ Marchisio et al. also studied S. salivarius spray and reported a decrease of recurrent AOM episodes from 43% to 13% among kids who were successfully colonized (54% of the treatment group).¹¹ Cárdenas et al. reported that a 6-month course of Lactobacillus salivarius-supplemented milk reduced the proportion of infants experiencing AOM episodes from 70% to 36%,¹² while Stecksén-Blicks et al. showed that among toddlers at day care centers, a 21-month course of Lactobacillus rhamnosus-supplemented milk significantly reduced the number of days of otitis media three-fold.¹³ Furthermore, evidence suggests that probiotic consumption reduced antibiotic usage and non-AOM infections.⁸ Side effects due to probiotic treatment were rare, although were reported to contribute to gastrointestinal symptoms (regurgitation, diarrhea, constipation), appetite changes and dry skin in the Cohen study.⁹

Secretory Otitis Media

Secretory otitis media (SOM), characterized by fluid accumulation, or effusion, in the middle ear cavity, is commonly a sequela of AOM.⁷ A double-blind pilot study with 60 children by Skovbjerg et al. showed that compared to placebo, a nasal spray containing Streptococcus sanguinis, but not L. rhamnosus, significantly increased spontaneous recovery,¹⁴ while Roos et al. saw decreases in SOM as well as AOM (reported above) with probiotic nasal spray administration.¹⁰ In an RCT of 22 children, Di Pierro et al. reported that oral delivery of Streptococcus salivarius K12 tablets reduced the frequency of episodes by 40% over 3 months, while also improving tone audiometry and palatine tonsil size.⁷ A recent investigation of Lactobacillus reuteri-infused drops by Kaytez et al. demonstrated reductions in histamine-induced effusions in a rat model.¹⁵ Transtympanic delivery of probiotics has been evaluated for safety in a chinchilla animal model and offers a promising opportunity for further mitigating middle ear inflammation.¹⁶

In summary, fluid products containing Lactobacillus strains appear to confer the greatest resistance to AOM and SOM episodes, but larger studies are required to investigate optimal populations and timing of delivery.

Oral Cavity

Oral Candidiasis

Infection of the oral cavity, most typically by Candida albicans, is common among elderly and immunocompromised populations. A meta-analysis by Ai et al. concluded that probiotics effectively reduced oral yeast counts, thus inhibiting candidiasis in elderly populations.¹⁷ Another study found that administering probiotic powder on dentures suppressed Candida colonization of the palate mucosa from 92% to 17%.¹⁸ An RCT of 65 adults by Li et al. showed that, compared to antifungals alone, a 4-week course of combination probiotic lozenge significantly reduced fungal load but not pain and hyperemia in Candida-associated stomatitis.¹⁹ A one week course of probiotic mouthrinse was as effective as chlorhexidine in effectively curbing Candida counts in children.²⁰ A single cohort study in 42 elderly, institutionalized women saw mild decreases in Candida after consumption of a commercial probiotic drink.²¹ Additionally, Lactobacillus-infused periodontal dressings improved bone repair in vitro and prevented candidiasis among patients with chronic generalized periodontitis.²² However, several RCTs have reported minimal clinical benefit despite depletion of Candida load. A 12-week lozenge treatment in 215 older adults did not significantly improve dental plaque or gingival inflammation, while a 16-week probiotic cheese regimen in 304 elderly participants did not alleviate oral pain.^23,24 Biofilm analysis of various Lactobacillus strains revealed antifungal properties that restrict Candida adherence and proliferation.²⁵ Altogether, these studies strongly suggest that probiotic treatments may effectively curb Candida colonization, however, further studies are needed to validate its use prophylactically or show significant improvement in clinical parameters.

Recurrent Aphthous Stomatitis

The oral microbiome has also been studied in the context of recurrent aphthous stomatitis (RAS), which is characterized by painful ulcerations.²⁶ Short-term and long-term regimens have shown efficacy. A 1-week course of Lactobacillus brevis lozenges diminished perilesional erythema, pain and burning symptoms in a randomized trial of 30 patients, while three month trial of oral Lactobacillus/Bifidobacterium sachets in a cohort of 45 randomized patients improved pain, but not average healing time, or number and size of lesions at 6 months.^26,27 However, an RCT of 19 patients did not reveal symptomatic benefit of a 3-month course of L. rhamnosus in an oral suspension.²⁸ Altogether, sustained delivery of probiotics in lozenge form appears to relieve, but not resolve, symptoms in RAS.

Oncology-Related

Radiation-Induced Oral Mucositis

Oral mucositis (OM) is characterized by progressing oral inflammation and ulceration that is a common consequence of radiation therapy (RT) and chemotherapy (CT), especially among patients with Head and Neck Cancer (HNC). In extreme cases, severe mucositis can result in dose-reduction and impact oncologic outcomes.

Clinical trials by Sharma and colleagues demonstrated that standard of care supportive treatment along with adjuvant L. brevis CD2 lozenge delivery was safe for immunocompromised patients and significantly decreased the incidence of severe OM among hematopoietic stem cell transplant (HSCT) patients from 98% (placebo) and 63% (palifermin) to 19% (probiotic intervention) and in HNC patients from 77% (placebo) to 52% (probiotic intervention).^29,30 Furthermore, in HNC patients, probiotic management improved rates of oncologic treatment completion by 22% and significantly lowered analgesic usage (narcotics and non-narcotics, combined, but not narcotics alone), although improvements in parenteral/enteral nutrition and QoL did not reach significance.³⁰ Probiotic treatment without standard of care, conversely, did not produce a significant benefit in a multicenter RCT in Italy, that was terminated early due to issues obtaining their probiotic agent.³¹ An RCT by Jiang et al. on 99 patients undergoing concurrent radio-chemotherapy for nasopharyngeal carcinoma revealed significant reductions in severe OM compared to placebo after bidaily consumption of probiotic capsules containing Bifidobacterium longum, Lactobacillus lactis, and Enterococcus faecium over the treatment course.³² Meta-analyses of these studies by Shu et al. concluded that probiotic treatments reduced the incidence and severity of OM in HNC patients. Although differences in cancer treatment completion did not reach significance, the authors attributed this to the fact that the patients in the study by Jiang et al. underwent intensity modulated radiation therapy which allows for better optimization of radiation delivery compared to traditional 2D radiotherapy techniques.³³

Similar to trends seen in other inflammatory conditions, oral mucositis is receptive to adjuvant probiotic management of symptoms, although larger studies are warranted.

Oral Cancer & Dysplasia

Host-microbiota interactions in the head and neck may contribute to precancerous dysplasia, similar to that seen in chronic Helicobacter pylori-induced gastric cancer. Existing data relating to oral dysplasia is limited to preclinical studies. Microbiome profiling has revealed potential microbial biomarkers of oral epithelia dysplasia,³⁴ oral carcinogenesis,³⁵ and head and neck squamous cell carcinoma.³⁶

Additionally, murine studies by Zhang et al. demonstrated that delivery of L. salivarius REN extracted from centenarians in China suppressed 4-nitroquioline 1-oxide-related inflammation, oxidative damage, and COX-2 expression, all implicated in oral carcinogenesis.³⁷ In vitro pathway analysis on an oral cancer cell line revealed that Lactobacillus plantarum strain may potentiate anticarcinogenic effects through PTEN upregulation and MAPK downregulation.³⁸ These preliminary studies support further prospective clinical investigation of probiotic interventions against oral carcinogenesis. Furthermore, a recent systematic review by Wan Mohd Kamaluddin et al. identified Acetobacter syzygii in addition to these Lactobacillus strains as promising agents for inhibiting oral carcinogenesis.³⁹

Voice Prosthesis

Silicone rubber voice prostheses are prone to colonization by microorganisms, most commonly streptococci and Candida species, which form biofilm layers that can compromise airflow and cause leakages.⁴⁰ Consequently, voice prostheses are replaced every 3 to 4 months.⁴¹ Although clinical studies are sparse, in vitro studies using artificial throat models (in which pump-driven media perfuse a tray of voice prostheses) have characterized pathogen inhibition by commensal probiotic strains. Delivery of Lactobacillus and Streptoccocus strains or their biosurfactants on artificial voice prostheses have yielded antimicrobial effects, suppressing biofilm formation and reducing airflow resistance.^41,42 In vitro studies using unpasteurized buttermilk and fermented milk reported depleted bacterial load, but conflicting results on yeast load.^43,44 Schwandt et al. showed that in vivo consumption of fermented milk (but not buttermilk) decreased yeast formation and more than tripled voice prosthesis lifespan.⁴⁴ These preliminary results suggest that probiotic management can offer a promising strategy for voice prosthesis maintenance.

Oro-nasopharyngeal Cavity

Adenoiditis, Tonsillitis

Probiotic management has proven promising in managing chronic adenoid and tonsillar inflammation in children. A cohort (n=41) of children with recurrent GAS pharyngotonsillitis had fewer and shorter episodes after a 3-month course of twice daily oral spray containing a suspension of S. salivarius and S. oralis compared to placebo controls (n=41).⁴⁵ A 30-day delivery of S. salivarius via nasal-douche reduced the frequency of episodes in children with chronic adenoiditis from 89% in the controls (n = 106) to 50% in the study cohort (n = 113).⁴⁶ Similar benefit of a 30-day course of S. salivarius has been observed in children with recurrent tonsilitis.⁴⁷ Although further studies are required to evaluate their preventative potential, probiotics appear to effectively suppress inflammatory symptoms.

Upper Respiratory Tract Infections

Probiotic therapies have been shown to offer some symptomatic relief in upper respiratory tract infections (URTIs). A two-study meta-analysis by Makino et al. totaling 142 healthy elderly participants concluded that consumption of probiotic yogurt (containing Lactobacillus bulgaricus and Streptococcus thermophilus) compared to milk significantly reduced URTIs and improved quality of life scores capturing eye, nose, and throat symptoms.⁴⁸ Lau et al. reported that in 219 pre-school children, a 10-month regimen using B. longum, compared to placebo, significantly reduced the duration of sore throat, but not fever, rhinorrhea and coughing after artificial inoculation (although this method may not generalize well).⁴⁹ In an RCT on 203 kids, Di Pierro et al. reported and 84% reduction in URTI incidence and 50% reduction in duration of symptoms, possibly mediated by increased salivary IgA, which was observed.⁵⁰ An RCT by Kumpu et al. on 194 children experiencing active respiratory or gastrointestinal infection revealed that consumption of L. rhamnosus GG-supplemented milk over 28 weeks modestly reduced the number of days of respiratory symptoms (congestion, rhinorrhea, sore throat), despite nonsignificant effects on nasopharyngeal viral loads and number of symptoms experienced.⁵¹ Recent reviews have reported that probiotic regimens significantly reduce the incidence of URTIs within pediatric populations and the duration of symptoms among adults, elderly populations and elite athletes.^52–54

Results on viral load (independent of symptoms) have been mixed. A pilot study by Tapiovaara et al. found that a 6-week regimen of L. rhamnosus GG-juice formulations in healthy adults did not significantly impact nasopharyngeal viral load after intranasal inoculation. Of note, the authors did report that viral load correlated with symptom scores.⁵⁵ Lehtoranta et al. reported that long-term administration of chewable probiotic tablets containing Lactobacillus and Bifidobacterium strains in military conscripts decreased picornavirus load at a 3-month timepoint, although the authors caution that seasonal timing may have been a confounder.⁵⁶ Altogether, the existing literature suggests that refined probiotic formulations offer some benefit in managing URTI symptoms and incidence in some populations, but further research is required to optimize delivery and investigate prophylactic potential.

Nasopharyngeal Bacterial Infection

The effects on pathogenic bacterial load, similar to those on viral load, have been mixed. Glück et al. reported that nasal colonization of Staphylococcus aureus, Streptococcus pneumoniae and beta-hemolytic streptococci decreased after a 3-week course of a fermented milk drink (containing Lactobacillus, Bifidobacterium, and Streptococcus).⁵⁷ Franz et al. found, however, that 4 weeks of consuming Lactobacillus casei-infused milk did not significantly impact S. aureus and S. pneumoniae load.⁵⁸ In summary, larger studies are needed to evaluate optimal delivery of probiotics for pathogenic deterrence.

Nasal Cavity

Allergic Rhinitis

Allergic rhinitis (AR) is characterized by IgE-mediated inflammatory responses in the nasal mucosa and affects approximately 10–30% of the general population.⁵⁹ A meta-analysis of 23 studies by Zajac et al. in 2015 found that probiotics, especially of milk and yogurt formulations, significantly improved Rhinitis Quality of Life (QoL) Questionnaire scores, although limited benefit was seen in Rhinitis Total Symptom Scores (TSS) and antigen-specific serum IgE levels.⁵⁹ A separate meta-analysis of 22 studies by Güvenç et al. in 2016 concluded clinical and immunologic benefit for treatment of AR using probiotic treatments, especially Lactobacillus paracasei strains.⁶⁰ A 2015 systematic review by Peng et al. on 11 RCTs reported that probiotic therapies improved quality of life and symptom scores, but not immunologic parameters (serum antige-specific IgE expression, Th1/Th2 ratio, eosinophil rates, etc.) in patients with AR. Furthermore, probiotics were not recommended for infants as a preventative measure for ectopic conditions.⁶¹

Jalali et al. conducted a crossover trial on 152 patients with persistent AR, and found that an 8-week regimen of probiotic capsules (consisting of Lactobacillus, Bifidobacteria and Streptococcus species) in addition to budesonide nasal spray significantly enhanced QoL measures, such as SF-36, and symptom scores, SNOT-22 and CARAT questionnaires.⁶² Another crossover study by Lue et al. among pediatric patients with perennial AR revealed that compared to levocetirizine alone, adjuvant capsules over 12 weeks significantly improved TSS scores and nasal peak expiratory flow rate, but not pediatric QoL measures.⁶³ Co-administration of Clostridium butyricum has also been reported to augment the effect of specific immunotherapy, improving symptom and medication scores, and suppressing specific IgE and Th2 cytokines, even after treatment cessation.⁶⁴ A freeze-dried formulation of B. longum and L. plantarum was shown to improve total nasal symptom scores and rhinitis control assessment test results as well as certain immunomarkers compared to placebo in a RCT cohort of 98 adults.⁶⁵ Among 20 patients who underwent immunotherapy for AR, limited effect on immunomarkers and clinical parameters was reported with the treatment of probiotic capsules versus placebo over 2 months.⁶⁶ Clinical trials in young children and other probiotic formulations are underway.^67,68

In summary, strong evidence exists for the benefit of probiotic treatments in a variety of modalities in the management of AR. Longer studies are required to assess long-term and prophylactic efficacy.

Chronic Rhinosinusitis

Disrupted microflora richness and diversity have been associated with chronic rhinosinusitis (CRS), and in their 2017 review, Psaltis and Wormald stated that probiotics were promising for CRS management, although the authors advocated for larger studies.⁶⁹ An RCT by Habermann et al. showed that a 6-month course of Enterococcus faecalis reduced acute exacerbations or CRS, and sustained benefit two months after stopping the regimen.⁷⁰ A non-randomized 8-week study using E. faecalis reported similar benefit in children, but shorter studies have not yielded such a dramatic benefit. A 4-week regimen of orally administered L. rhamnosus improved symptom severity (SNOT-20), but not frequency of acute episodes,⁷¹ while an RCT by Mårtensson et al. did not show significant improvement in SNOT-22 symptom scores after a 2-week course of lactic acid bacteria nasal spray.⁷² Recent characterization of the oral microbiome in CRS patients has revealed its utility in diagnosis and potentially implications of oral/dental hygiene in CRS pathogenesis.⁷³ Altogether, the evidence suggests that longer courses of probiotic management (>1 month) does provide CRS relief beyond acute episodes.

Inflammatory Non-allergic Rhinitis

Unlike AR, inflammatory non-allergic rhinitis (INAR) is not driven by IgE signaling. In a retrospective, multicenter study of 93 patients, Gelardi et al. concluded that compared to corticosteroid, oral antihistamine, and isotonic saline combination therapy, adjuvant probiotic delivery improved symptom severity, endoscopic features, and nasal cytology.⁷⁴ At this time, additional studies in a randomized manner are recommended for INAR evaluation before clinical recommendations can be made.

Other

Wound Healing, Nasal Packing

Several studies have investigated probiotic interventions for surgical infections, although not specifically in Otolaryngology. A meta-analysis by Liu et al. in 2017 reported that combination multi-strain probiotics significantly reduced surgical site infections in colorectal surgery.⁷⁵ In an RCT of 64 adults undergoing surgical removal of molars, probiotic treatment was shown to reduce disturbed sleep, sick-leave from work and perceived sense of swelling, but did not drastically improve objective measures of post-operative recovery (swelling or wound healing index) or analgesic use.⁷⁶ Preliminary data from Peral et al. on 80 burned patients suggested that a probiotic bandage was more effective than Silver sulphadiazine (microbicidal agent) in reducing the pathogenic bacterial load and improving granulation and wound healing processes among subjects with infected third-degree burns.⁷⁷ Similarly, animal studies demonstrated wound healing benefit with an NO-producing probiotic patch,⁷⁸ and L. reuteri extract suspensions⁷⁹. A preliminary murine study by Gokodgan et al. showed that probiotic nasal packing decreased bacterial load, although they experienced poorer bleeding and inflammation signs, histopatholoigcally.⁸⁰ Given this promising preclinical evidence, clinical trials are needed to investigate the efficacy of prophylactic infection treatment.

Dental disorders

Gingivitis & Periodontitis

Probiotics have been studied in the context of dental and gingival conditions, especially as an alternative to chlorhexidine mouthrinse, which has considerable side effects, including taste alteration and teeth staining. In their recent meta-analysis of a heterogenous cohort of 10 RCT, Ho et al. reported improved clinical outcomes with adjunctive 2–4 week probiotic treatments at 3- and 12-month timepoints but not at 6- and 9-months.⁸¹ A separate meta-analysis of 10 RCTs on gingivitis by Akram et al. reported clinical benefit of probiotics in half of the studies, although did not find a significant difference in outcomes among L. reuteri therapies and could not evaluate across all studies because of heterogeneity.⁸² Bustamante et al. reported that, although results from their recent meta-analysis was inconclusive due to heterogenous agents and regimens, evidence for adjunctive probiotic management of gingivitis and periodontitis.⁸³ A 2016 systematic review by Prasad et al. over 8 studies concluded that compared to chlorhexidine solution, probiotic mouthrinses significantly improved gingival index (GI) and maintained comparable plaque index (PI) scores.⁸⁴ Clinical benefit compared to placebo has also been shown in the context of 8-week administration of freeze-dried Lactobacillus tablets,⁸⁵ 4-week course of heat-treated Lactobacillus tablets,⁸⁶ and a chewing gum formulation taken over 2 weeks.⁸⁷ Limited effect has been reported with lozenge-based formulations. An RCT by Shah et al. reported, however, that no clinical difference was observed between 2 week courses of probiotic lozenge alone, antibiotics alone, and both in combination.⁸⁸ Additionally, separate studies on adjuvant lozenges containing Lactobacillus strains did not improve clinical outcomes.^89,90 Altogether, the evidence for probiotic usage is strong, but larger studies are warranted to evaluate optimal delivery and timing.

Peri-Implantitis

Evidence for probiotic use in peri-implantitis has yielded mixed results. A recent meta-analysis of 7 RCTs by Gao et al. reported that Lactobacillus probiotics did not improve clinical outcomes such as bleeding or plaque index.⁹¹ Among these studies, a placebo-controlled crossover study in 34 subjects by Flichy-Fernández et al. found that a 30-day course of L. reuteri tablets significantly decreased PI, probing depth and crevicular fluid, but not GI in patients with peri-implantitis.⁹² Similarly, Galofré et al. showed that a 30-day regimen of probiotic lozenges (compared to placebo) with mechanical therapy reduced mucositis and peri-implantitis.⁹³ Hallström et al. reported, however, that a 3 month course of L. reuteri lozenges did not produce any clinical benefit compared to placebo.⁹⁴ A 1-month course of L. reuteri tablets taken once daily also did not show any benefit.⁹⁵ The presence of the implant as a permanent fixture and a constant source of inflammation may minimize any effect of probiotics in the management of peri-implantitis.

Dental Caries and Halitosis

Compelling evidence exists for anticariogenic properties of probiotic tablets, lozenges, powders and even an ice cream formulation.^96–100 Probiotic gums, mouthrinses and lozenges for halitosis have had variable efficacy in improving clinical parameters such volatile sulfur compound (VSC) levels and organoleptic assessments, although these studies suffer from small sample sizes (20–25 subjects).^101–103 In their meta-analysis, Bustamante et al. reported that probiotic regimens can effectively treat halitosis and reduce pathogen load in the development of dental caries.⁸³ A meta-analysis of three studies from 2012–2016 concluded that probiotics significantly reduced organoleptic scores but not VSC levels.¹⁰⁴ A recent 64-person RCT by Benic et al reported that a 1-month course of S. salivarius lozenges was shown to have a sustained improvement in volatile sulfur compounds at a 3-month time point compared to placebo.¹⁰⁵

IMPLICATIONS FOR PRACTICE

In summary, probiotic therapies may offer clinical benefit in a variety of contexts within the field of otolaryngology. While considerable research exists for the short-term efficacy of some inflammatory conditions of the oral cavity, auditory and nasal cavities, further investigation is warranted for evaluation of long-term outcomes and pathogenic deterrence.

At this time, we conclude that strong evidence exists for:

• AR and CRS exacerbations (symptoms)

• Gingivitis, periodontitis

• Dental caries

At this time, evidence is mostly supportive and supports further investigation:

• AOM and SOM (larger studies needed)

• Oral candidiasis (for clinical outcomes as most studies focus on yeast depletion)

• RAS (larger studies needed)

• RIOM (larger studies needed)

• Adenoiditis, Tonsillitis (larger studies needed)

• URTIs (larger studies needed in some populations)

At this time, existing clinical evidence is insufficient to recommend probiotics for:

• INAR (need RCTs)Nasopharyngeal infections (larger studies needed)

• Peri-implantitis and halitosis (other probiotic agents or methods of delivery needed)

Preclinical studies inform the need for clinical studies and RCTs for intervening on:

• Oral Dysplasia

• Voice prostheses maintenance

• Wound healing and nasal packing

At this time, meta-analyses and robust trials support the use of probiotics in managing nasal symptoms in AR and CRS, but further studies are needed to evaluate prophylaxis efficacy. Diverse probiotic agents have shown efficacy in inflammatory periodontal conditions such as gingivitis and periodontitis and inhibited the formation of dental caries.

Probiotic products have also been shown to benefit the clinical management of AOM, SOM, oral candidiasis, RAS, chronic adenoiditis and tonsillitis, URTIs and RIOM. However, most of the studies suffer from small sample sizes.

Larger, more robust RCTs are lacking for probiotic use in INAR. Given mixed results in some of the probiotic interventions, we cannot recommend them without further investigation on optimal strains and applications for the following conditions: nasopharyngeal infections, peri-implantitis, and halitosis.

Lastly, promising preclinical studies support further clinical investigation of probiotics in the context of oral dysplasia, voice prosthesis maintenance, wound healing and nasal packing.