BioAmicus Complete for Functional Gastrointestinal Symptoms in Infants Aged 0 to 24 Months

caregiver burden and health care visits. Modulating the developing gut microbiome with probiotics may alleviate these symptoms. BioAmicus Complete is a multistrain probiotic designed to support a healthy intestinal microbiota; systematic clinical evaluation is warranted to determine its efficacy and safety in infants.

Objectives:

Primary: Determine whether BioAmicus Complete improves overall gastrointestinal symptoms versus usual care, measured by change in IGSQ total score between baseline and study end.

Exploratory (microbiome): Characterize changes in stool microbiome composition and diversity across the study period.

Secondary: Compare groups on symptom domain scores (e.g., colic, regurgitation, stooling patterns), caregiver burden/quality of life, health care utilization and antibiotic exposure, growth parameters, and safety outcomes (adverse events, serious adverse events, and product-related events).

Significance: Findings will inform whether BioAmicus Complete can be recommended as an adjunct to routine care for infant functional gastrointestinal symptoms and will provide preliminary insights into microbiome changes associated with symptom improvement.

• BioAmicus Complete (Dietary supplement), also known as Multistrain Probiotic (BioAmicus Complete): Oral liquid probiotic (multistrain) administered by caregivers per protocol/label for 42 days to infants with functional GI symptoms. Given as drops by mouth; dosing and administration instructions per protocol. No other probiotic products allowed during the study. Concomitant medications and routine management may be used as clinically indicated. Adherence is recorded; lot/batch number captured.
• Usual Care (No Probiotic) (Other), also known as Standard care, Routine clinical management: Standard clinical management for infant functional gastrointestinal symptoms per local practice. No probiotic supplementation is provided during the study period. Participants follow the same visit and assessment schedule as the intervention arm. Concomitant medications and supportive care may be used as clinically indicated.

Primary outcomes

• Change from Baseline in Infant Gastrointestinal Symptom Questionnaire (IGSQ) Total Score at Day 42 [Baseline to Day 42]: IGSQ is a 13-item, caregiver-reported questionnaire (total score 13-65; higher scores indicate worse symptoms). Change is calculated as Day 42 minus baseline; a negative change indicates improvement
• Stool Microbiome - Change in Alpha Diversity (Shannon, Chao1) [Baseline to Day 42]: 16S rRNA gene sequencing of stool at baseline and Day 42; alpha diversity indices computed and change analyzed within and between groups.

Secondary outcomes

• Change in Stool Frequency Based on Infant & Toddler GI Symptom Questionnaire from Baseline to Day 42 [Baseline to Day 42]: Stool frequency is assessed. Responses range from 1 (≤2 times/week) to 5 (>3 times/day). Higher scores indicate more frequent bowel movements (diarrhea tendency), while lower scores indicate infrequent stools (constipation). Improvement is defined as movement toward the normal category (1 bowel movement/day).
• Change in Stool Consistency Using the Brussels Infant and Toddler Stool Scale (BITSS) from Baseline to Day 42 [Up to Day 42]: Stool consistency is assessed using the Brussels Infant and Toddler Stool Scale (BITSS), with five categories: 1 = watery, 2 = soft, 3 = formed, 4 = hard, 5 = inconsistent. Category 3 (formed) is considered normal. Scores below 3 represent looser stools (diarrhea tendency), while scores above 3 represent harder stools (constipation tendency). Improvement is defined as a ≥1-category change toward formed stool.
• Stool Microbiome - Between-Group Difference in Beta Diversity (PERMANOVA) [Day 42]: Bray-Curtis and UniFrac distances used to assess community differences between groups; hypothesis testing via PERMANOVA.
• Change in Frequency of Regurgitation and Vomiting Episodes from Baseline to Day 42 [Baseline to Day 42]: Regurgitation and vomiting are assessed using Questions. Frequency is reported on a 7-point ordinal scale (0 = never to 6 = >5 times/day). Higher scores indicate more frequent regurgitation/vomiting (worse outcome). Improvement is defined as a reduction of ≥1 category on the frequency scale.
• Change in Colic Symptoms Based on Infant & Toddler GI Symptom Questionnaire from Baseline to Day 42 [Baseline to Day 42]: Colic is assessed, based on Wessel's criteria (≥3 hours/day, ≥3 days/week, for ≥3 weeks). Responses are scored on a binary scale (Yes/No). Presence of colic is considered a positive outcome at baseline. Improvement is defined as resolution of criteria (reduction below threshold)

Sex: All, ages: 0 Days to 24 Months

Inclusion Criteria:

* Age 0-24 months at enrollment.
* Infant has clinician-assessed functional gastrointestinal symptoms (e.g., colic/irritability, regurgitation, constipation, loose stools), judged suitable for study participation.
* Parent or legal guardian provides written informed consent and agrees to comply with study procedures (questionnaires/diaries and sample collection, if applicable).
* Caregivers agree to avoid other probiotic products during the study period, except as directed by the study team.

Exclusion Criteria:

* Major congenital gastrointestinal anomalies or known chronic gastrointestinal diseases requiring ongoing prescription therapy (e.g., Hirschsprung disease, inflammatory bowel disease, short-bowel syndrome).
* Clinically unstable condition or severe/critical illness that could interfere with participation or safety in the opinion of the investigator.
* Known or suspected primary or secondary immunodeficiency, or current immunosuppressive therapy.
* History of severe allergy or hypersensitivity to components of the investigational product.
* Recent use of systemic antibiotics within 14 days prior to baseline, or use of probiotic supplements within 14 days prior to baseline (per protocol).
* Participation in another interventional clinical trial within 30 days prior to enrollment or during the study.
* Any condition that, in the investigator's judgment, would make the participant unsuitable for the study or confound outcome assessments.