NCT07498127

Effects of Probiotics on Respiratory Tract Infections in Children: A Randomized, Placebo-Controlled Interventional Study

• Status: Enrolling By Invitation
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Min-Tze LIONG · Academic / Other
• Sex: All
• Age: 3 Months – 6 Years
• Healthy volunteers: Not accepted

Summary

This study is a 14-day, randomized, double-blind, placebo-controlled trial involving children aged 3 months to 6 years who meet clinical diagnostic criteria for mild to moderate upper respiratory tract infection (URTI). Participants are randomized to receive either a mixed probiotic preparation (Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V) or a placebo. The primary clinical outcome assessed is the duration and severity of respiratory symptoms. Secondary outcomes include changes in gut microbiota composition, intestinal immune markers, and quality of life. To investigate potential mechanisms, fecal samples are collected before and after intervention for metagenomic sequencing to analyze microbial diversity and composition, alongside immunological assessments such as sIgA and calprotectin.

Detailed description

Upper respiratory tract infection (URTI) is one of the most common pediatric illnesses, particularly affecting young children whose immune systems are still developing. Children under six years of age are especially susceptible to frequent infections, which can negatively impact growth, daily functioning, and overall quality of life. Although most URTIs are mild and self-limiting, recurrent or prolonged symptoms can lead to increased healthcare utilization, caregiver burden, and inappropriate antibiotic use, contributing to antimicrobial resistance. Therefore, safe and effective interventions that can reduce symptom severity and duration are of significant clinical importance. The pathogenesis of URTI is multifactorial, involving viral exposure, host immune responses, and microbial ecosystem balance. Increasing evidence highlights the role of the gut-lung axis, a bidirectional communication pathway between the intestinal microbiota and the respiratory system. The gut microbiota plays a critical role in immune system maturation and regulation. Disruptions in microbial balance (dysbiosis) may impair immune defenses, making children more vulnerable to respiratory infections. Probiotics, defined as live microorganisms that confer health benefits when administered in adequate amounts, have shown promise in modulating the gut microbiota and enhancing immune responses. Specific strains such as Lactobacillus rhamnosus and Bifidobacterium breve have been associated with improved mucosal immunity, including increased production of secretory immunoglobulin A (sIgA), regulation of inflammatory responses, and enhanced resistance to pathogens. These effects may translate into reduced severity and shorter duration of respiratory symptoms. Several biological mechanisms have been proposed to explain how probiotics exert beneficial effects on respiratory health. The gastrointestinal and respiratory tracts are interconnected components of the mucosal immune system. Activation of gut-associated lymphoid tissue by probiotics can stimulate systemic immune responses, including the production of cytokines and immunoglobulins that enhance respiratory defense. Additionally, probiotics may influence metabolic pathways through the production of short-chain fatty acids, which have anti-inflammatory and immunomodulatory properties. Maintaining microbial balance in both the gut and respiratory tract is essential for optimal immune function. Children with respiratory infections often exhibit reduced levels of beneficial gut bacteria, such as Lactobacillus and Bifidobacterium, along with altered immune markers. Probiotic supplementation may help restore this balance, improve intestinal barrier function, and enhance systemic immunity. Clinical benefits reported in previous studies include reduced symptom severity, faster recovery, and improved quality of life. Importantly, probiotics are generally well tolerated and have a strong safety profile in pediatric populations. Based on this scientific rationale, the present study focuses on children aged 3 months to 6 years diagnosed with mild to moderate URTI. Participants will receive a fixed-dose combination of Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V (1 × 10¹⁰ CFU/day) or a placebo for 14 consecutive days. Clinical outcomes, including symptom duration and severity, will be evaluated alongside safety measures. To further elucidate underlying mechanisms, fecal samples will be collected to assess gut microbiota composition using metagenomic sequencing, examining parameters such as alpha diversity, beta diversity, and relative abundance of key taxa. In addition, intestinal immune markers, including calprotectin (CALP) and secretory IgA (sIgA), will be measured. Quality of life will also be assessed using a pediatric respiratory questionnaire. Through the integration of clinical, microbiological, and immunological data, this study aims to clarify the therapeutic potential and mechanistic basis of probiotic intervention in pediatric URTI.

Conditions

• URTI

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Probiotic	Daily 6-drops of 1 × 10\^10 CFU containing Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V in MCT oil
DIETARY_SUPPLEMENT	Placebo Control	Daily 6-drops of MCT oil containing non-GMO corn starch

Timeline

• Start date: 2026-02-01
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2026-03-27
• Last updated: 2026-04-02

Locations

2 sites across 2 countries: China, Malaysia