Dataset Information

Impact of Streptococcus salivarius K12 on Nasopharyngeal and Saliva Microbiome: A Randomized Controlled Trial.

ABSTRACT:

Background

Probiotic lactobacilli have been ineffective in preventing acute otitis media. In contrast to lactobacilli, alpha-hemolytic streptococci belong to the core microbiome of nasopharynx.

Methods

We investigated the effects of Streptococcus salivarius K12 probiotic on the saliva and nasopharyngeal microbiome in 121 children attending daycare. Children were randomly allocated to receive oral K12 product for 1 month or no treatment. We obtained saliva and nasopharyngeal samples at study entry, at 1 and 2 months. The next-generation sequencing of the bacterial 16S gene was performed.

Results

After the intervention, the diversity of saliva or nasopharyngeal microbiome did not differ between groups. The proportion of children with any otopathogen did not differ between the groups. At 1 month, the abundance of otopathogens in nasopharynx was lower in K12 group compared with that in control children (34% vs. 55%, P = 0.037). When we compared each otopathogen separately, Moraxella was the only group lower in the treatment group. We could not verify the reduction of Moraxella when an alternative Human Oral Microbiome Database taxonomy database was used. In children receiving K12 product, the mean abundance of S. salivarius was greater in saliva after the intervention (0.9% vs. 2.0%, P = 0.009).

Conclusions

The use of S. salivarius K12 probiotic appeared to be safe because it did not disrupt the normal microbiome in young children. Even though a short-term colonization of S. salivarius was observed in the saliva, the impact of S. salivarius K12 probiotic on the otopathogens in nasopharyngeal microbiome remained uncertain.

SUBMITTER: Sarlin S

PROVIDER: S-EPMC8043514 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceNew approaches for the prevention of acute otitis media (AOM), the most common reason for antibiotic use in children, are needed.ObjectiveTo assess the efficacy of the Streptococcus salivarius K12 oral probiotics in the primary prevention of AOM.Design, setting, and participantsThis double-blind, randomized placebo-controlled clinical trial was conducted from August 1, 2020, to May 31, 2021, at 50 day care centers in the Oulu region of Finland. A total of 827 children aged 1 to 6 years attending day care were included. The exclusion criteria consisted of ongoing antimicrobial prophylaxis or immunodeficiency. The follow-up time was 6 months and was completed on May 31, 2021. Data were analyzed from October 24, 2022, to September 16, 2023, based on intention to treat.InterventionEligible participants were randomly allocated to receive 1 daily dose of a S salivarius K12 product or placebo every evening for 6 months. A daily dose was defined as 1 sachet of soluble oral powder for children younger than 3 years or 1 chewable tablet for children 3 years or older containing 1 × 109 colony-forming units of S salivarius K12.Main outcomes and measuresThe primary outcome was the proportion of children with at least 1 episode of AOM requiring antimicrobial therapy within 6 months of randomization. All physician visits and purchases of antimicrobial drugs were retrieved from the electronic national medical record and prescription register. The primary outcome was met if the legal guardian had purchased an antimicrobial prescription for AOM.ResultsA total of 827 children with a mean (SD) age of 4.1 (1.6) years (433 boys [52.4%]) were randomized to S salivarius K12 oral products (n = 413) or placebo (n = 414). Thirty-four children (8.2%) in the S salivarius group and 24 children (5.8%) in the placebo group experienced at least 1 episode of AOM requiring antimicrobial therapy during the 6-month follow-up period (relative risk, 1.42 [95% CI, 0.86-2.34]; proportion difference, -2.44% [95% CI, -5.94% to 1.09%]; P = .17). Time to first AOM episode did not differ between the groups (174 [95% CI, 171-177] days in the S salivarius group vs 176 [95% CI, 173-179] days in the placebo group; P = .18).Conclusions and relevanceIn this randomized placebo-controlled clinical trial, the daily use of the S salivarius K12 products for 6 months did not reduce the occurrence of AOM. New approaches for primary prevention of AOM among children are needed.Trial registrationClinicalTrialsRegister.eu Identifier: 2020-001076-14.

Project description:Streptococcus salivarius is an early colonizer of human oral and nasopharyngeal epithelia, and strain K12 has reported probiotic effects. An emerging paradigm indicates that commensal bacteria downregulate immune responses through the action on NF-kappaB signaling pathways, but additional mechanisms underlying probiotic actions are not well understood. Our objective here was to identify host genes specifically targeted by K12 by comparing their responses with responses elicited by pathogens and to determine if S. salivarius modulates epithelial cell immune responses. RNA was extracted from human bronchial epithelial cells (16HBE14O- cells) cocultured with K12 or bacterial pathogens. cDNA was hybridized to a human 21K oligonucleotide-based array. Data were analyzed using ArrayPipe, InnateDB, PANTHER, and oPOSSUM. Interleukin 8 (IL-8) and growth-regulated oncogene alpha (Groalpha) secretion were determined by enzyme-linked immunosorbent assay. It was demonstrated that S. salivarius K12 specifically altered the expression of 565 host genes, particularly those involved in multiple innate defense pathways, general epithelial cell function and homeostasis, cytoskeletal remodeling, cell development and migration, and signaling pathways. It inhibited baseline IL-8 secretion and IL-8 responses to LL-37, Pseudomonas aeruginosa, and flagellin in epithelial cells and attenuated Groalpha secretion in response to flagellin. Immunosuppression was coincident with the inhibition of activation of the NF-kappaB pathway. Thus, the commensal and probiotic behaviors of S. salivarius K12 are proposed to be due to the organism (i) eliciting no proinflammatory response, (ii) stimulating an anti-inflammatory response, and (iii) modulating genes associated with adhesion to the epithelial layer and homeostasis. S. salivarius K12 might thereby ensure that it is tolerated by the host and maintained on the epithelial surface while actively protecting the host from inflammation and apoptosis induced by pathogens.