Milk Oriented Microbiota

Study Overview
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Brief Summary
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The purpose of this study is to determine if supplementing healthy term infants delivered vaginally who consume breast milk, formula, or both with a probiotic for 21 consecutive days increases levels of bacteria in infants' stool.

Detailed Description
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The purpose of phase 1 of this two phase clinical trial is to determine: 1) the effect of decreasing levels of human milk oligosaccharides on fecal B.infantis during and after 21 days of supplementation with Evolve activated B.infantis using exclusively breastfed, mixed-fed and exclusively formula-fed infants; 2) determine the effect of Evolve activated B.infantis on fecal B.infantis levels in exclusively breastfed infants compared to pre-supplementation levels.

Official Title
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Establishing a Milk Oriented Microbiota in Healthy Term Infants

Conditions
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Microbial Colonization

Intervention / Treatment
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* Dietary Supplement: Bifidobacterium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with infants age 8 to 12 weeks Term infants born >37 weeks gestation Mother-infant pairs who live within a 20-mile radius from UC Davis campus in Davis, CA or within a 20-mile UCDMC Women and infants who live in one location Infants born vaginally Infants who are either exclusively formula-fed, exclusively breastfed or mixed-fed Women who are mixed and formula feeding their infants who are willing to switch infant formulas and use the study's infant formula (Earth's Best Organic Infant Formula With Iron, Earth's Best) throughout the first two months of the study Women who are breastfeeding but introduce infant formula to their infants during the first two months of the study who are willing to use the study's infant formula (Earth's Best Organic Infant Formula With Iron, Earth's Best) for the first two months of the study Exclusion Criteria: Women who have lived in the United States or other developed nation for less than 10 consecutive years Multiple infants born to one mother Plan to feed infants solid foods before infants turn 5 months of age Family history of cow milk or soy allergy and/or infants allergic to cow milk protein or soy Infants born by C-section Infants born with medical complications such as: respiratory distress syndrome, birth defects, and infection Infants who have taken antibiotics 4 weeks before enrollment and more than one course of antibiotics since birth Infants who have taken probiotics since birth Plan to administer probiotics to infants or use of probiotics other than the study supplement by infants for the first two months of the study Mothers who have a chronic metabolic disease or obesity Mothers who currently smoke or plan to resume smoking during the study period Infants who consume solid foods or other liquids other than breastmilk, infant formula or water

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The feeding patterns of eighty eligible infants (8 to 12 weeks in age) will be characterized based on a 7-day diet record that will be filled out by their mothers during the 7-day lead-in period starting with Day -7 and ending with Day -1. Of the eighty infants, twenty will be exclusive breast feeders (BF), twenty will be exclusive formula feeders (FF) and forty will be mixed-feeders (MF). Infants in all three feeding groups will consume B. infantis for twenty-one consecutive days. Participants will then enter the observational phase until their infant turns 1 year old.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Exclusively breastfed<br>Exclusive breastfeeding will be defined at screening as infants who have not consumed any infant formula after 7 days postnatal and have been exclusively breastfed without formula between day 7 of life through the end on the Lead-in period. ). Infants will consume B. infantis for twenty-one consecutive days. | Dietary Supplement: Bifidobacterium<br>* Each B. infantis (strain: BIEVC001) dose will be provided in one 625 mg sachet delivering 156 mg of live bacteria at a dose of 9x10^9 CFU plus 469 mg of pharmaceutical-grade lactose as the excipient and dispensed to participants by the study personnel.<br>* Other names: B. infantis;|
| Active Comparator: Exclusively formula fed<br>Exclusive formula feeding is defined at screening as infants who consume only infant formula between day 7 of life through the end on the Lead-in period. Infants will consume B. infantis for twenty-one consecutive days. | Dietary Supplement: Bifidobacterium<br>* Each B. infantis (strain: BIEVC001) dose will be provided in one 625 mg sachet delivering 156 mg of live bacteria at a dose of 9x10^9 CFU plus 469 mg of pharmaceutical-grade lactose as the excipient and dispensed to participants by the study personnel.<br>* Other names: B. infantis;|
| Active Comparator: Mixed fed<br>Mixed feeding is defined at screening as infants who consume a combination of infant formula and breast milk between day 7 of life through the end on the Lead-in period. Infants will consume B. infantis for twenty-one consecutive days. | Dietary Supplement: Bifidobacterium<br>* Each B. infantis (strain: BIEVC001) dose will be provided in one 625 mg sachet delivering 156 mg of live bacteria at a dose of 9x10^9 CFU plus 469 mg of pharmaceutical-grade lactose as the excipient and dispensed to participants by the study personnel.<br>* Other names: B. infantis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant fecal B. infantis | The change in infant fecal B. infantis before, during and after supplementation. | Change from baseline to day 280 | 
| Infant fecal Bifidobacterium | The change in infant fecal Bifidobacterium before, during, and after supplementation. | Change from baseline to day 280 | 
| Infant fecal total bacteria | The change in infant fecal total bacteria before, during and after supplementation. | Change from baseline to day 280 | 
| Infant fecal microbiome | The change in infant fecal microbiome before, during and after supplementation. | Change from baseline to day 280 | 
| Infant gastrointestinal symptoms | Gastrointestinal symptoms and related symptoms (discomfort passing bowel movements, vomiting, constipation, colic or irritability) before, during and after supplementation will be determined and reported daily by parental self-report questionnaire. | Change from baseline to day 50 | 
| Infant health status | General health status of the infant such as occurrence of any illness, health care visits for sickness, fever, antibiotic and medication use and parental assessments of infant's overall health. | Change from baseline to day 280 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal secretor status | Determine the relationship between human milk oligosaccharides in breast milk and infant fecal microbiome. | Change from baseline to day 280 | 
| Infant fecal sialic acid concentrations | The change in infant fecal sialic acid and fucose concentrations before, during and after supplementation in infant stool samples. | Change from baseline to day 280 | 
| Infant fecal microbiome and lifestyle | Determine the relationship between the following factors determined by self-report questionnaires: parity, maternal and infant antibiotic intake and maternal use of antimicrobials, infant intake of formula; and the change infant fecal microbiome. | Change from baseline to day 280 | 
| Infant weight | Determine the relationship between infant weight and change in fecal microbiome. | Change from baseline to day 280 | 
| Infant fecal short chain fatty acids | Determine the relationship between fecal short chain fatty acids and fecal microbiome. | Change from baseline to day 280 | 
| Infant gastrointestinal function | Determine the relationship between GI function (fecal inflammatory, GI barrier mediators, LPS) and fecal microbiome. | Change from baseline to day 280 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infants, Probiotic, B. Infantis