Publication Details
Abstract
Background: Recurrent common cold-like and upper-respiratory symptoms create a substantial functional burden in healthy adults, athletes, children and healthcare-associated populations. Lactococcus lactis JCM5805 has been evaluated in multiple randomized trials using inactivated oral preparations, with symptom endpoints commonly linked to its pDC–interferon immunobiology. The present study integrates those clinical findings with a standardized JCM5805-derived lysate platform designed for reproducible oral formulation. Methods: A three-batch biphasic lysate process was characterized for phase-ratio reproducibility, soluble-fraction purification, reconstitution stability, viable-cell control, moisture and water activity. In parallel, randomized trials and meta-analytic evidence published through September 2026 were synthesized with emphasis on cough, feverishness, sore throat, nasal symptoms, upper respiratory illness, school absence and fatigue. Results: Fixed-ratio recombination reduced the coefficient of variation of the soluble:insoluble dry-matter ratio from 26.2% to 1.3% and lowered the 24 h sedimentation-volume ratio from 25.2±3.0% to 8.3±0.3%. Final powder water activity was 0.223±0.015. Clinical evidence shows a recurring pattern of reduced symptom-positive days in selected settings: a 2015 winter RCT in 213 adults reported fewer cough and feverishness days; a 2016 RCT in 396 healthy adults reported fewer sore-throat and cough days; a 2018 athlete trial reported fewer URTI-positive days (39 vs 56), sneezing/runny-nose days (36 vs 52) and fatigue-positive days (110 vs 128); and a 2022 Vietnamese schoolchild trial found lower early-period absence due to upper respiratory or gastrointestinal illness and fewer fever-positive days. A 2025 individual-participant meta-analysis of 555 participants found mean differences of −0.69 days/28 days for cough and −0.26 days/28 days for feverishness. More recent trials provide context on heterogeneity: in mild COVID-19 the composite symptom score was similar between groups, while viral load decreased earlier and smell/taste recovery showed a day-specific difference; in a 2026 healthcare-associated cohort, fever and fatigue days were lower with intake. Conclusion: Across diverse randomized studies, JCM5805 has shown a reproducible signal for selected cold-like and infection-related symptom endpoints, particularly cough, feverishness and upper-respiratory symptom days. A tightly standardized lysate platform can support future formulation-specific trials with prespecified symptom diaries, pDC biomarkers and exposure-response analysis.