David W Cleary | PubMed Health

PubMed2026

BLIS study: a feasibility randomised controlled trial assessing compliance, acceptability and colonisation with different dosing regimens of the probiotic supplement Streptococcus salivarius K12 (Bactoblis) in adults in England.

OBJECTIVES: Streptococcus salivarius K12 (SsK12) is a bacterium used as a probiotic with some evidence for preventing acute sore throat/tonsillitis, but the optimal dosing strategy is unclear. This study aimed to evaluate two dosing regimens of SsK12 to establish (a) the prevalence and duration of colonisation with SsK12 and (b) the acceptability and feasibility of these regimens. DESIGN: A randomised, non-blinded feasibility trial. SETTING: Primary care in the south of England. PARTICIPANTS: Adults with ≥2 episodes of sore throat within the 3 years before recruitment. INTERVENTIONS: Participants were randomised to take SsK12 lozenges once weekly or daily over 14 days. MAIN OUTCOME MEASURES: The primary outcome was the prevalence and duration of colonisation with SsK12. This was determined by real-time PCR conducted on self-taken whole-mouth swabs provided by participants at baseline and on days 2, 7, 14, 21 and 35. Secondary outcomes were the compliance and acceptability of the two SsK12 dosing regimens, based on questionnaire data. RESULTS: 53 participants were recruited (26 randomised to weekly and 27 to daily dosing) between 26 April and 5 December 2023. All swabs were returned by 65.4% (17/26) and 70.4% (19/27) of the weekly and daily groups respectively. Swabs at all timepoints from participants with PCR positives observed at baseline (two and four from the weekly and daily group, respectively) were excluded. Therefore, swabs from 23 participants in the weekly and 22 in the daily group did not have evidence of baseline colonisation and were included in the microbiology analysis. SsK12 colonisation was found in 59.1% (13/22, 95% CI 38.6% to 79.6%) of samples in both groups on day 2; in 13.6% (3/22, 95% CI 0.0% to 28.0%) and 85.7% (18/21, 95% CI 70.8% to 100.0%) of the weekly and daily groups, respectively, on day 7; in 19.1% (4/21, 95% CI 2.3% to 35.8%) and 59.1% (13/22, 95% CI 38.6% to 79.6%), respectively, on day 14; and in only one participant (weekly group) on days 21 and 35. The dosing regimen was reported as easy to follow by 85.0% (17/20, 95% CI 69.4% to 100.0%) of the weekly and 96.2% (25/26, 95% CI 88.8% to 100.0%) of the daily dosing groups. CONCLUSIONS: SsK12 colonisation was more prevalent with daily dosing; however, colonisation was not maintained when dosing stopped. Both dosing regimens were acceptable to participants. These findings support the use of daily dosing in a future trial to evaluate the efficacy of SsK12 in preventing recurrence of sore throat/tonsillitis. TRIAL REGISTRATION NUMBER: NCT04297878.

Humans↗

PubMed2025

Controlled human infection model of Neisseria lactamica in late pregnancy investigating mother-to-infant transmission in the UK: a single-arm pilot trial.

BACKGROUND: The infant respiratory microbiome is derived largely from the mother and is associated with downstream health and disease. Manipulating maternal respiratory flora peripartum to influence the infant microbiome has not previously been investigated. Neisseria lactamica is a harmless pharyngeal commensal that correlates inversely with Neisseria meningitidis carriage and disease. Intranasal N lactamica inoculation is a safe and well characterised controlled human infection model (CHIM) in non-pregnant healthy adults. We hypothesised that N lactamica inoculation in pregnancy induces mother-to-infant N lactamica transmission postnatally. METHODS: In this single-arm trial, 21 healthy pregnant female participants aged 18 years or older were inoculated at 36-38 weeks' gestation with 105 colony-forming units of N lactamica Y92-1009 at University Hospital Southampton Clinical Research Facility, Southampton, UK. N lactamica selective culture, genome sequencing, and serological testing were performed on maternal and infant oral, nasopharyngeal, breastmilk, and serum samples over 15 weeks postpartum. Seven female participants naturally colonised with N lactamica at baseline were followed up, but not inoculated. Oral samples were obtained from 12 cohabiting siblings younger than 5 years. The primary endpoint was infant N lactamica colonisation. This study was registered with ClinicalTrials.gov, NCT04784845, and is now complete. FINDINGS: Between Oct 25, 2021, and March 7, 2022, 31 adult female participants (median age 33·5 years [range 23·1-39·9]; 26 [84%] were White, British) were screened and enrolled, of whom seven were already colonised with N lactamica. After exclusion of three participants, 21 participants were inoculated, of whom 15 (71%) became N lactamica-colonised, and no sustained N lactamica Y92-1009 transmission to their infants was observed. Conversely, non-Y92-1009 N lactamica strain sharing was observed in four (57%) of seven uninoculated mother-sibling pairs, and Moraxella catarrhalis strain sharing in nine (38%) of 24 mother-infant pairs completing the study. Anti-N lactamica serum IgG titres increased in seven (88%) of eight N lactamica Y92-1009-colonised female participants, but none of their infants (where paired sera were available). There were no serious adverse reactions to the inoculum. INTERPRETATION: As the world's first perinatal CHIM, this trial demonstrates that this model in pregnancy is feasible, and that N lactamica Y92-1009 can safely and efficiently colonise pregnant individuals. Lack of sustained mother-to-infant N lactamica transmission, despite evidence supporting mother-to-infant M catarrhalis and sibling-to-mother N lactamica transmission, challenges conventional perceptions of infants as passive recipients of maternal microbes, suggesting that respiratory commensal transmission is selective and microbe-specific. FUNDING: Medical Research Council and National Institute for Health Research Southampton Biomedical Research Centre.

Adult↗