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

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 × 10 9 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.

Lactic acid bacteria as probiotics for the nose?

“…Further application of this strain in CRS patients is thus of great interest and is currently being explored by our research group. To the best of our knowledge, only two published studies have yet investigated the effects of topical probiotic treatment in CRS patients, by using a probiotic nasal spray (M artensson et al, 2017) or sinus irrigations (Endam et al, 2020). The randomized, double-blinded study by M artensson and colleagues investigated the previously mentioned nasal spray device with a mixture of 13 honeybee LAB (10 11 CFU ml -1 ) in CRSsNP patients, of which 14 out of 20 participants had previously undergone surgery, compared with placebo (M artensson et al, 2017).…”

“…As previously described, a possible explanation might be that the LAB strains that were used are not adapted to the URT. In the other study, CRS patients with previous undergone FESS were recruited and received intranasal irrigation with Lactococcus lactis W136 for two weeks (Endam et al, 2020). The origin of L. lactis W136 is not well-described in the paper, but Lactococcus is often detected in URT microbiome studies in healthy subjects (Laufer et al, 2011;Pettigrew et al, 2012;De Boeck et al, 2017).…”

Topical Microbial Therapeutics against Respiratory Viral Infections

“…twice a day over the course of 2 weeks was well-tolerated by healthy volunteers and no adverse effects were reported. Similarly, intranasal application of L. lactis W136 in chronic rhinosinusitis patients in an open-label pilot trial was not associated with any major adverse events [90].…”

“…Furthermore, lessons learned from probiotic interventions in the gastrointestinal tract suggest that the resident host microbiome can determine the intervention outcomes [94]. Of note, intranasal application of L. lactis W136 improved chronic rhinosinusitis disease scores and increased the relative abundance of D. pigrum in the sinus microbiome of patients [90]. It is thus pivotal to consider how interactions with the resident respiratory microbiota can shape the outcomes of local interventions with beneficial bacteria, which will require larger, well-designed follow-up clinical trials with detailed microbiome read-outs.…”

“…Indeed, the available evidence at molecular and cellular level and in animal models remains to be substantiated by large-scale clinical trials. So far, feasibility and safety of local administration of beneficial bacteria into the airways, for instance, in the form of a nasal spray, have been demonstrated in several studies distinctly focusing on bacterial pathogens or ill-delineated respiratory conditions [5,90]. Well-designed clinical studies are urgently needed to define the optimal probiotic strains and mixtures, doses, and formulation for application in the airways against the most important respiratory viruses, as well as the key target populations (see Outstanding Questions).…”