Intranasal Application of Lactococcus lactis W136 Is Safe in Chronic Rhinosinusitis Patients With Previous Sinus Surgery

Leandra Mfuna Endam, Saud Alromaih, Emmanuel Gonzalez, Joaquin Madrenas, Benoit Cousineau, Axel E Renteria, Martin Desrosiers, Leandra Mfuna Endam, Saud Alromaih, Emmanuel Gonzalez, Joaquin Madrenas, Benoit Cousineau, Axel E Renteria, Martin Desrosiers

Abstract

Objective: Modulation of the dysbiotic gut microbiome with "healthy" bacteria via a stool transplant or supplementation is increasingly practiced, however this approach has not been explored in the nasal passages. We wished to verify whether Lactococcus lactis W136 (L. lactis W136) bacteria could be safely applied via irrigation to the nasal and sinus passages in individuals with chronic rhinosinusitis (CRS) with previous undergone endoscopic sinus surgery, and whether this was accompanied by bacterial community flora modification. Study Design: Prospective open-label pilot trial of safety and feasibility. Setting: Academic tertiary hospital center. Subjects and Methods: Twenty-four patients with CRS refractory to previous medical and surgical therapy received a 14-day course of BID sinus irrigations containing 1.2 × 109 CFU live L. lactis W136. Patients were monitored for safety using questionnaire, sinus endoscopy, otoscopy, UPSIT-40 smell testing, and endoscopically-obtained conventional sinus culture and a swab for 16S microbiome profiling. Results: All 24 patients receiving at least one treatment successfully completed treatment. L. lactis W136 probiotic treatment was safe, with no major adverse events or new infections. Treatment was associated with improvement in sinus symptoms, QOL, and mucosal scores, which remained improved during the subsequent 14-day observation period. Microbiome changes associated with treatment were limited to an increase of the pathobiont Dolosigranulum pigrum, a bacteria identified as potentially beneficial in the upper airways. Subgroup analysis suggested differences in microbiomes and responses for CRSsNP and CRSwNP phenotypes, but these did not attain significance. Conclusion: Intranasal irrigation of live L. lactis W136 bacteria to patients with refractory chronic rhinosinusitis was safe, and was associated with effects on symptoms, mucosal aspect and microbiome composition. Intranasal bacteria may thus find a role as a treatment strategy for CRS. Clinical Trials Registration: www.ClinicalTrials.gov. identifier: NCT04048174.

Keywords: CRS treatment; Lactococcus lactis W136; chronic rhinosinusitis (CRS); probiotics; refractory CRS; sinus irrigation; sinus microbiome.

Copyright © 2020 Endam, Alromaih, Gonzalez, Madrenas, Cousineau, Renteria and Desrosiers.

Figures

Figure 1
Figure 1
CONSORT statement.
Figure 2
Figure 2
Timeline of probiotic trial. Study protocol showing initial 14 days saline-only washout period; 14 days of L. lactis W136 followed by 14 day saline-only observational period (D, Day).
Figure 3
Figure 3
Effect of L. lactis W136 on total nasal symptom score (n = 24). Time-weighted average scores over the study period from day 0 (D0) to day 28 (D28).
Figure 4
Figure 4
Effect of L. lactis W136 on individual nasal symptoms (0–3 scale). (A) Facial pain; (B) headache; (C) nasal congestion; (D) need to blow nose; and (E) post-nasal drip (n = 24). Time-weighted average scores over the study period from day 0 (D0) to day 28 (D28).
Figure 5
Figure 5
Effect of L. lactis W136 on SNOT-22. Mean of total score of the 22 items from quality of life questionnaire (n = 24). Time-weighted average scores over the study period from day 0 (D0) to day 28 (D28).
Figure 6
Figure 6
Effect of L Lactis W136 on sinus endoscopy: Total POSE score. (n = 24).
Figure 7
Figure 7
Impact of L. lactis W136 treatment on olfaction. UPSIT-40 scores prior to (Day 0) and immediately following treatment (Day 14) presented individually for all patients (n = 24) (D, Day).
Figure 8
Figure 8
Sinus microbial analysis of patients before and after ESS. (A) A comparison of alpha diversity indices (Shannon and inverse Simpson). (B) Compared relative abundance (from raw counts). (C) Canonical analysis of principal coordinates of taxa abundance from raw counts. No significant differences between the groups were observed in alpha and beta diversities. (D) Differentially abundant OTUs (FDR < 0.05) between the pre-surgery (pre, n = 24) and post-surgery (post, n = 24) groups. The main axis represents the fold change (log2) in relative abundance of significantly different OTUs between the two groups and their normalized counts. Values represent mean score for all enrolled patients (n = 24). Change in microbiome is calculated from day 0 to day 14 period (D, Day, D0, introduction of probiotic; D14, end of treatment).
Figure 9
Figure 9
Sinus microbial analysis of patients without and with nasal polyps (CRSsNP, n = 7; CRSwNP, n = 17). (A) Comparison of alpha diversity indices (Shannon and inverse Simpson). (B) Comparison of relative abundance (from raw counts). (C) Canonical analysis of principal coordinates of taxa abundance from raw counts. Significant differences between the groups was observed in beta diversities (PERMANOVA, p < 0.01). (D) Differentially abundant OTUs (FDR < 0.05) between patients with polyps and patients without. The main axis represents the fold change (log2) in relative abundance of significantly different OTUs between the two groups and their normalized counts.
Figure 10
Figure 10
Sinus microbial analysis of microbiome modifications before and after L. lactis W136 administration. (A) For CRSsNP (n = 7) and (B) For CRSwNP (n = 17) subgroups. Differentially abundant OTUs (FDR < 0.05) between before and after L. lactis W136 administration. The main axis represents the fold change (log2) in relative abundance of significantly different OTUs between the two groups and their normalized counts.

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