To Investigate the Effects of Bifidobacterium Animalis Subsp. Lactis XLTG11 on Growth and Development, Incidence of Allergy and Immune Function in Infants

Phase 2RecruitingNCT07490587

Min-Tze LIONG366 enrolled

Overview

This study is a 180-day randomized, double-blind, placebo-controlled trial involving healthy infants and young children under 3 years of age with elevated allergy risk. Participants are randomized to receive either Bifidobacterium animalis subsp. lactis XLTG11 probiotic or placebo daily. The primary clinical outcomes assessed are incidence and day-level burden of allergic, respiratory, and gastrointestinal symptoms. To investigate potential mechanisms, fecal samples were collected pre- and post-intervention for shotgun metagenomic sequencing to analyze changes in gut microbiota composition, functional pathways (KEGG, COG, GO), and mucosal immune markers (β-defensin 2, LL-37, calprotectin, sIgA) associated with clinical improvements.

Early childhood represents a critical developmental window during which the gut microbiome, immune system, and mucosal defense pathways undergo coordinated maturation. Dysregulation during this period contributes substantially to allergic sensitization, respiratory morbidity, and gastrointestinal disorders, which collectively represent major pediatric health burdens worldwide. Infants and young children frequently experience high symptom burden across these domains, reflecting vulnerability to microbial instability and disrupted mucosal homeostasis. The underlying causes are multifactorial, involving dietary transitions, environmental exposures, infections, and immune programming. Growing evidence suggests that disruptions in gut microbial stability, rather than merely compositional changes, may influence susceptibility to multi-system symptoms through interconnected immune and metabolic pathways. The gastrointestinal tract and respiratory tract are interconnected components of the common mucosal immune system. Immune responses generated in the gut-associated lymphoid tissue can influence distant mucosal sites, including the respiratory epithelium and skin-associated lymphoid tissues. Probiotics can stimulate gut-associated lymphoid tissue, leading to enhanced production of antimicrobial peptides (β-defensin 2, LL-37), immunoglobulins, cytokines, and short-chain fatty acids. These immune mediators circulate systemically and contribute to strengthened epithelial barrier function and immune surveillance at multiple sites. In addition, maintaining functional stability of the gut microbial ecosystem, rather than simply increasing diversity, may be essential for safeguarding against stress-driven metabolic reprogramming and pathobiont expansion during early life. Children affected by allergic, respiratory, and gastrointestinal symptoms often exhibit instability in microbial community architecture, including bloom of opportunistic taxa (Escherichia coli, Klebsiella, Enterococcus faecalis, Ruminococcus gnavus, Ruminococcus torques) and depletion of short-chain fatty acid-producing fermenters (Eubacterium rectale, Anaerostipes hadrus, Coprococcus species). Dysbiosis and functional instability weaken both local and systemic immunity, particularly through reduced production of antimicrobial peptides and impaired epithelial barrier function. Probiotic supplementation with Bifidobacterium animalis subsp. lactis XLTG11 may help restore microbial functional homeostasis, suppress pathobiont-associated trajectories, and enhance the host's innate mucosal defense profile. Based on current scientific understanding, this 180-day randomized controlled trial enrolled healthy infants and young children under 3 years of age with elevated allergy risk. Participants received daily Bifidobacterium animalis subsp. lactis XLTG11 (1 × 10¹⁰ CFU) or placebo to evaluate clinical benefits across allergic, respiratory, and gastrointestinal domains, as well as safety outcomes including growth parameters and bowel habits. Additionally, shotgun metagenomic sequencing was performed on fecal samples collected at baseline and 180 days to assess changes in gut microbiota composition, taxonomic remodeling, KEGG pathways, KEGG enrichment patterns, COG functional profiles, and Gene Ontology terms. Mucosal innate immune markers (β-defensin 2, LL-37, calprotectin, secretory IgA) were quantified to assess host immune modulation. Through these integrated clinical, immunological, and multi-omic metagenomic measures, the study aims to clarify whether B. animalis subsp. lactis XLTG11 reduces symptom burden by buffering against microbiome functional instability, preserving genomic and metabolic homeostasis, reinforcing epithelial innate defense, and suppressing pathobiont emergence-rather than by driving compositional expansion alone. This functional buffering mechanism represents a novel paradigm for probiotic action during the critical early-life window of immune and microbiome development.

Eligibility

Sex: ALLMin age: 0 MonthsMax age: 36 MonthsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Term infants are 37≤ gestational age \< 42 weeks, and the birth weight is between 2500g and 4000g (only applicable to 0\~12 months old) * Breastfed or mixed-fed healthy infants and young children, aged 0\~3 (inclusive) years old, gender is not limited * The allergy risk score calculated by the Infant Allergy Risk Assessment Table is ≥6(Refer to the National Center for Women and Children's Health, Chinese Center for Disease Control and Prevention: Investigation and Research on Allergy Symptoms and Risk Factors in Infants and Young Children) * Family primary guardians agree to collect fecal samples of infants and young children during this study * Have not used antibiotics in the past month * Have not used probiotics in the past three months * Family primary guardians committed not to add additional Bifidobacterium dietary supplements to infants and young children during the intervention period * The guardians of the enrolled subjects agree to participate in this interventional study and sign a written informed consent form, and are able to understand and fill in forms such as infant diaries as required * Signed informed consent and willing to follow up at the time specified in the trial Exclusion Criteria: * The mother of the infant has a history of diabetes, hepatitis B, HIV and other infectious diseases * Clinicians diagnosed with allergic diseases (including but not limited to eczema, asthma, allergic proctocolitis, allergic rhinitis, hay fever, etc.) at the time of enrollment of infants and young children * Infants and young children who are known to be allergic to the ingredients of probiotic products * In the opinion of the investigator, the subject has other reasons that make it unsuitable to participate in this clinical study

Outcomes

Primary Outcomes

Allergy symptoms in children upon administration of probiotic or placebo as assessed via clinical questionnaire

Differences in severity of allergy symptoms in children upon administration of probiotic or placebo, assessed using a hospital-based clinical questionnaire, that captures the frequency and duration of symptoms over the observation period, where composite scores is the cumulative number and duration of reported episodes, with lower values indicating a lower overall symptom burden and better respiratory status.

Time frame: Day-0, Day-180

Secondary Outcomes

Microbiota profiles of fecal samples in young children upon administration of probiotic or placebo as assessed via 16s rRNA and metagenomics gene sequencing

Differences in microbiota profiles in fecal sample of children upon administration of probiotic or placebo

Time frame: Day-0, day-180

Gut immune biomarkers of fecal samples in young children upon administration of probiotic or placebo as assessed via Enzyme-Linked Immunosorbent Assay (ELISA)

Differences in gut immune biomarkers in fecal sample of children upon administration of probiotic or placebo, such as secretory immunoglobulin A (sIgA).

Time frame: Day-0, Day-180

Defecation frequency in children upon administration of probiotic or placebo as assessed via daily stool diary

Differences in defecation frequency (stools per day) in children upon administration of probiotic or placebo, assessed using a structured daily stool diary completed by parents/guardians.

Time frame: Day-0, day-180

Stool consistency (Bristol Stool Scale characteristics) in children upon administration of probiotic or placebo as assessed via standardized stool form classification

Differences in stool consistency in children upon administration of probiotic or placebo, assessed using the Bristol Stool Form Scale (type 1-7), with parents/guardians recording daily stool characteristics, where abnormal stools are characterized by types 1-2 (constipation) and types 6-7 (diarrhea).

Time frame: Day-0, Day-180

Growth index (age- and sex-standardized Z-score) in children upon administration of probiotic or placebo as assessed via anthropometric measurements.

Differences in growth outcomes between groups were assessed using standardized anthropometric measurements where Z-scores are calculated based on the World Health Organization Child Growth Standards, and the scores represent standardized deviations from the reference population mean, with a theoretical range typically spanning approximately -6 to +6, where higher values indicate greater growth relative to age- and sex-specific norms.

Time frame: Day-0, Day-180

To Investigate the Effects of Bifidobacterium Animalis Subsp. Lactis XLTG11 on Growth and Development, Incidence of Allergy and Immune Function in Infants

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts