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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 4  |  Page : 329-333

Current understanding of probiotics and sinonasal inflammation: A review


Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia

Date of Submission25-Feb-2020
Date of Decision12-Apr-2020
Date of Acceptance27-Apr-2020
Date of Web Publication25-Jun-2020

Correspondence Address:
Nouf Mohammad Aloraini
College of Medicine, King Saud University, Riyadh 13216, Saudi Arabia
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JNSM.JNSM_14_20

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  Abstract 


The complex interplay between commensal sinonasal microbiota and pathogenic bacteria contributes to the development of sinonasal inflammatory diseases. This review describes the rationale, effectiveness, and safety of probiotics in sinonasal inflammatory diseases. In vitro and animal clinical trials demonstrated a promising effect of probiotics in decreasing inflammation and the proportion of pathologic bacteria and improving the outcome. However, human studies involving chronic rhinosinusitis (CRS) patients did not exert any significant effect in reducing the symptoms, except in one study reported improvements in CRS exacerbations. This review concluded that up to now, the value of probiotics usage is not well understood, and future research aiming to extend the understanding of it will contribute to enhance the effectiveness of probiotic use in sinonasal inflammatory diseases.

Keywords: Chronic rhinosinusitis, microbiota, probiotics, sinonasal inflammatory diseases


How to cite this article:
Alromaih SR, Aloraini NM. Current understanding of probiotics and sinonasal inflammation: A review. J Nat Sci Med 2020;3:329-33

How to cite this URL:
Alromaih SR, Aloraini NM. Current understanding of probiotics and sinonasal inflammation: A review. J Nat Sci Med [serial online] 2020 [cited 2020 Oct 24];3:329-33. Available from: https://www.jnsmonline.org/text.asp?2020/3/4/329/287697




  Introduction Top


Sinonasal inflammatory diseases are distinguished by nasal and paranasal sinuses mucosal inflammation and include a spectrum of diseases, one of which is chronic rhinosinusitis (CRS). CRS is diagnosed if the disease duration has exceeded 12 weeks, and it can be accompanied nasal polyps.[1] CRS is a widespread disease worldwide having a high symptomatic and financial strain and has been proven to have a detrimental effect on patients' standard daily activities.[2],[3] The European Position Paper on Rhinosinusitis and Nasal Polyposis (EP3OS) is one of the approved and widely used guidelines. The EP3OS guidelines suggest having a minimum of two of the following symptoms as a criterion to diagnose CRS: nasal obstruction, nasal secretions, hyposmia, and facial pain in conjunction with endoscopic or imaging findings.[1] Although a substantial number of studies that have discussed the pathophysiology of CRS have shown its heterogeneous pathogenesis, the exact mechanism remains to be identified, which has limited the available treatment options.[4],[5]

Probiotics are described as “live microorganisms capable of conferring health benefits to the host, when administered in adequate amounts.”[6] Probiotics should not be confused with prebiotics which are indigestible fibers that are consumed by the beneficial bacteria existing in the body. Probiotics are utilized to treat both gastrointestinal (GI) and non-GI diseases. The literature that helped prove their use is frequently contradicting, particularly for non-GI diseases.[7] There are multiple data supporting the beneficial effects of using probiotics to treat acute diarrhea, pouchitis, and atopic eczema in children and for the treatment of genitourinary infections.[8],[9],[10],[11] Moreover, a recent review done to measure the effect of probiotics in regulating inflammatory diseases suggested that the current scientific literature supports the addition of probiotics for treating both mucosal and systemic inflammatory diseases.[3],[12]

The use of probiotics in CRS emerged after a study that was done in 2009, which revealed a positive bacterial culture in healthy appearing paransaal sinuses visualized through endoscope. This supported the raising hypothesis that bacteria can exist in both healthy and diseased statuses.[13] Several studies have demonstrated that CRS patients will have pathological bacteria as the main population residing their sinuses such as Staphylococcus aureus (SA), Corynebacterium spp., and various anaerobes (Bacteroides spp., Peptostreptococcus spp., Prevotella, and Fusobacterium) and reductions in the populations of commensal microorganisms such as Acinetobacter johnsonii, Lactobacillus sakei, and Propionibacterium acnes.[13],[14],[15],[16]

In this review, we discuss the value of probiotics usage bothin vitro andin vivo and summarize the available clinical data and animal studies on the effects of probiotics on sinonasal inflammation [Table 1] and [Table 2].
Table 1: Animal studies evaluating the sinonasal effects of probiotics

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Table 2: Clinical studies evaluating the sinonasal effects of probiotics in humans

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  In Vitro Studies Top


Multiplein vitro papers have been published proving the efficacy of probiotics. A recent study published in 2018 was conducted to investigate Lactobacillus species in treating Moraxella catarrhalis, an upper respiratory tract infection (URTI) agent. The Lactobacillus strains were developed at 37°C in the Man, Rogosa and Sharpe medium, while M. catarrhalis was injected into Mueller Hinton broth and cultured at 37°C, after which the direct effect of Lactobacillus over M. catarrhalis was tested through spot analysis, which showed strong activity of Lactobacillus against M. catarrhalis. Many of the widely known Lactobacillus strains such as Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, and Lactobacillus plantarum have demonstrated strong activity and very clear inhibition zones that were similar to the effects of an antiseptic agent for oropharyngeal infections. Furthermore, L. rhamnosus GG reduced the gene expression of interleukin (IL)-1 β, IL-8, MUC5AC, and tumor necrosis factor-alpha (TNF-α) and competed with M. catarrhalis for adhesion to human airway epithelial Calu-3 cells.[17] A similar study was done using a peripheral blood mononuclear cell challenge model to test the effect of probiotics on IL-10, TNF-α, and a primary epithelial cell module from patients' biopsy samples. They used Lactococcus lactis, a Gram-positive probiotic that has demonstrated an IL-10-inducing capacity with the ability to decrease TNF alpha levels. These findings indicate the potential anti-inflammatory properties of these probiotic organisms, which could be used in futurein vitro studies.[18] Thesein vitro studies support the therapeutic potential of probiotic organisms against upper respiratory tract pathogens.


  Animal Studies Top


Animal studies were performed to obtain insights into the therapeutic potential of topical probiotics. A research done in 2012 generated a murine model of a sinus infection similar to that affecting the human population and observed the numbers goblet cell and mucin secretion. Mice were subdivided into four groups (5 animals per group), and one of these groups was treated with both antimicrobial agents and Corynebacterium tuberculostearicum. The histopathological examination revealed a prominent increase in goblet cell numbers and increase in the level of mucin secretion, after which this group received L. sakei, which led to a reduction in the inflammation of the sinonasal mucosa reaching to a state that resembles the control group, in contrast to the other groups.[14] Similarly, another study was done aiming to define the probiotic effect of Staphylococcus epidermidis (SE) on SA, since SA is known to be a key pathogen for CRS. This study was performed on 20 C57/BL6 mice which received intranasal administration of SE, SA, or a combination of SA and SE, followed by measurement of goblet cells. The findings showed that pretreatment with SE reduced the production of inflammatory cells in the sinonasal mucosa, in comparison to the cell numbers after SA treatment.[19] Another study that was performed in 2015 to measure the effect of Bifidobacterium breve in BALB/c mice by evaluating its effects on the immunoregulatory process and nasal symptoms of allergic rhinitis (AR) established using ovalbumin. They evaluated the efficacy of B. breve through assessment of nasal manifestations (e.g. nasal rubbing and sneezing), serum immunoglobulin and cytokine levels, and the splenic percentages of CD4 + CD25 + Foxp3 + regulatory T (Treg) cells. The study concluded that oral consumption of B. breve shortly after being born reduced the severity of nasal manifestations of AR and increased the number of CD4 + CD25 + Foxp3 + Treg cells. These animal researches have emphasized the key role of probiotics composition in defining the microbiome response and result in the sinus mucosa.[20]


  Studies on Oral Probiotics Top


Local delivery and systemic delivery are the two main focus areas of research for these agents. Two clinical trials have been done to evaluate the systemic effect of probiotic usage in CRS. A double-blind placebo-controlled multicenter study was done to assess the effectiveness of Enterococcus faecalis bacteria in reducing acute relapse in patients with CRS. Their study sample included 157 patients with CRS, with half of the patients receiving 3 × 30 drops/day of E. faecalis serological Group D for a period of 6 months, while the other half received placebo. Their main criterion for assessment was the frequency of relapses during the treatment duration. They used a 3-level rating scale: mild, no impairment in daily life activities; moderate, impairment in daily life activities despite the use of decongestant and/or antibiotics; and severe, documented clinical symptoms of CRS over more than 2 days of bed rest despite using antibiotics. They reported a reduction in the number of symptomatic episodes of CRS in patients who received a 6-month course of oral E. faecalis, with the benefit sustained for 8 months posttreatment.[21] In contrast, the second study was a randomized controlled clinical trial on the effectiveness of oral probiotics using a chewable tablet consisting of 500 million active cells of L. rhamnosus strain R0011 in 39 CRS patients with endoscopic proof of nasal or sinus inflammation (University of Miami endoscopic staging). The participants took these tablets twice a day for 8 weeks, while a control group of 38 patients received placebo. For the evaluation of symptom baseline and follow-up assessments, they used the 20-item Sinonasal Outcome Test (SNOT-20), assessed symptom frequency using a general questionnaire, and asked patients to maintain a treatment logbook to document compliance. However, their results showed no significant benefit of probiotic treatment over placebo.[22] Nevertheless, both of these studies did not report any significant side effects, indicating that probiotics possibly have a good safety profile.

Otherin vivo studies have investigated the effectiveness of probiotics in URTIs and rhinitis. To assess the effectiveness of probiotics in URTI, it was a multiple center, double-blinded, randomized controlled trial involving 1072 volunteers with the average age being 76 years. The volunteers received a dairy product that was fermented containing L. casei DN-114 001 (L. casei) for 3 months and were then followed up for 1 month. The results were evaluated based on the individuals' clinical manifestations, and the blood samples showed that those who received L. casei had a lesser time span of URTI symptoms than the control group.[23] Another double-blinded, randomized clinical trial performed on 173 participants who had a subjective seasonal allergies aimed to assess whether Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 could improve the participants' quality of life. To evaluate the effectiveness of this probiotic combination, the authors used the Mini Rhinoconjunctivitis Quality of Life Questionnaire, since it is a validated tool used to evaluate the quality of life in people who have allergies. They found a significant improvement in the rhinoconjunctivitis-specific quality of life during allergy season.[24] In addition, in a systemic review conducted in 2016 to measure the effect of probiotics in treating AR, the authors included 22 randomized, double-blinded, placebo-controlled trials involving all age groups. In their review, AR was confirmed using IgE evaluations and/or skin-prick tests, and they reported the possible evidence of the benefit of probiotics in treating AR, particularly with SAR and the Lactobacillus paracasei P-33 strains, which were confirmed to show improvements in both clinical and immunological reports.[25]


  Studies on Topical Probiotics Top


To this day, only one study has tested the effect of topical probiotic usage in CRS patients, while most of the other clinical trials tested the effects of probiotics in other diseases. The effects of topical honeybee were tested using lactic acid bacteria (LAB) on induction of nasal symptoms. The study recruited 22 healthy individuals who received a formula containing 13 LAB species with a concentration of 1 × 1011 colony-forming units/mL in a spray device that delivered 100 μL per actuation, and the participants were instructed to receive two sprays for each nostril. All participants completed the SNOT-22 form before and after receiving the active spray, had E-Swab samples taken from the middle meatus using a rhinoscope, underwent nasal lavage on every visit, and completed the Total Nasal Symptoms Score evaluation 24 h after receiving the active spray. The authors concluded that the honeybee LAB microbiome did not cause any inflammatory reaction or disrupt the commensal bacteria and was well tolerated overall.[26] A randomized double-blinded study was done to assess the effectiveness of the topical LAB microbiome in treating CRS. Twenty-one patients with CRSsNP (disease was verified by endoscopy or computed tomography) participated in their study, which used the same protocol except that LAB was administered for a duration of 2 weeks only. Other than that, they applied the same measures as the author's previous study, such as the SNOT-20 form being used as a primary measurement of outcome. They reported no statistically significant differences in the severity of symptoms or the inflammatory activity, but their results were restricted by their small sample size and the short duration of probiotic usage, making it very difficult to draw any conclusions.[27] Furthermore, a clinical trial was done to experiment the consequence of peroral consumption of the probiotic L. rhamnosus GG on the human rhinovirus (HRV) load in nasopharyngeal lavage samples of experimental HRV infection in 59 volunteers. They used nasopharyngeal lavage samples to detect the viral load through polymerase chain reaction and a symptom dairy to analyze the effectiveness of L. rhamnosus GG, which showed no significant difference between the experimental group and the placebo group.[28]


  Conclusion Top


Assessment of the interactions between microorganisms in in vitro, animal, and human studies and assessment of microorganisms modulating immune responses in the nasal epithelium may be an interesting new approach. Thein vitro and animal studies proved that probiotics were effective in preventing relapses and decreasing the severity of symptoms in sinonasal inflammation. However, studies on human CRS patients showed that probiotics were safe but showed no evidence of significant improvement, except in one study wherein oral probiotics were reported to reduce the number of acute exacerbations for 8 months. In contrast, human probiotic trials performed on AR and upper respiratory infection patients show significant evidence of improvement in these diseases. These inconsistent findings could be due to the difficulty of measuring the effectiveness due to the wide ranges of probiotics available that could be used in different studies. Future research aiming to extend the understanding probiotic role and effectiveness in patients with sinonasal inflammatory diseases is needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Abreu NA, Nagalingam NA, Song Y, Roediger FC, Pletcher SD, Goldberg AN, et al. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med 2012;4:151ra124.  Back to cited text no. 14
    
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Aurora R, Chatterjee D, Hentzleman J, Prasad G, Sindwani R, Sanford T. Contrasting the microbiomes from healthy volunteers and patients with chronic rhinosinusitis. JAMA Otolaryngol Head Neck Surg 2013;139:1328-38.  Back to cited text no. 15
    
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