Infant Microbiota and Probiotic Intake Study

NCT02457338 | Active Not Recruiting

• 1 other identifier: 631099
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if supplementing healthy term infants delivered by C-section or vaginal delivery who only consume breastmilk with a probiotic for 21 consecutive days increases levels of bacteria in infants' stool.

Conditions

Healthy

Keywords

C-section; Infants; Probiotic; B. infantis; Microbiota; Gut; Breast milk; Vaginal

Outcome Measures

Primary Outcomes (6)

• Infant fecal B. infantis

  Measure the change from baseline, during supplementation, and post supplementation

  baseline, days 10, 14, 17, 21, 25, 29, 32, 40, 50, 60

• Infant fecal Bifidobacterium

  Measure the change from baseline, during supplementation, and post supplementation

  baseline, days 10, 14, 17, 21, 25, 29, 32, 40, 50, 60

• Infant fecal total bacteria

  Measure the change from baseline, during supplementation, and post supplementation

  baseline, days 10, 14, 17, 21, 25, 29, 32, 40, 50, 60

• Infant fecal microbiota

  Measure the change from baseline, during supplementation, and post supplementation

  baseline, days 10, 14, 17, 21, 25, 29, 32, 40, 50, 60

• Incidence of Adverse Events and Treatments

  Gastrointestinal symptoms and related symptoms (discomfort passing bowel movements, vomiting, constipation, colic or irritability) before, during and after B. infantis supplementation will be determined and reported daily by parental self-report questionnaire. 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.

  Baseline-days 60

• Incidence of Adverse Events and Treatments

  Gastrointestinal symptoms and related symptoms (diarrhea, vomiting, constipation, colic, irritability) after B. infantis supplementation will be determined and reported parental self-report questionnaire. 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.

  Months 4, 6, 8, 10, 12, 18 and 24

Secondary Outcomes (11)

• Infant fecal bacteria oligosaccharide consumption

  days 7, 14, 21, 32, 60

• Infant fecal sialic acid concentrations

  baseline, days 10, 14, 17, 21, 25, 29, 32, 40, 50, 60

• Maternal fecal B. infantis, Bifidobacterium, total bacteria, and microbiota composition

  baseline, day 60

• Infant weight

  birth, hospital discharge, days 15, 33, 61

• Fecal inflammatory mediators

  Baseline-days 60

Study Arms (2)

Supplement Group

EXPERIMENTAL

This group will receive probiotic B. infantis supplementation, plus standard care and lactation consultation.

Dietary Supplement: Bifidobacterium

Control Group

NO INTERVENTION

This group will receive standard care plus lactation consultation only.

Interventions

Bifidobacterium DIETARY_SUPPLEMENT

Also known as: B. infantis

Supplement Group

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, non-smoking women and their infants
• Who are pregnant in their third trimester OR have delivered by C-section or vaginal birth within the past 7 days
• Patients who live within a 20-mile radius from University of California Davis Medical Center (UCDMC) or a 20-mile radius from UC Davis Campus in Davis, California.
• Plan to exclusively breastfeed their infants for at least 3 months
• Infants: 0-7 days old, delivered by C-section or vaginal delivery, born \>37 weeks gestation, without medical complications that would preclude breastfeeding or alter gut microbiota

You may not qualify if:

• Infants born with medical complications such as: respiratory distress syndrome, birth defects, and infection
• Infants who have taken antibiotics for more than 72 hours of life
• Infants who have consume formula feedings after day 7 of life
• Mothers and their infants who are not discharged from the hospital by day 4 of life due to complications
• Plan to administer probiotics to infants or use of probiotics other than the study supplement by infants anytime throughout the study duration
• Women who have had any breast surgery or injury within the past 5 years that would reduce the chance of successful exclusive breastfeeding
• Mothers who have a chronic metabolic disease or obesity

Sponsors & Collaborators

• University of California, Davis: lead
• Evolve BioSystems, Inc.: collaborator

Study Sites (1)

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Related Publications (30)

• Prior E, Santhakumaran S, Gale C, Philipps LH, Modi N, Hyde MJ. Breastfeeding after cesarean delivery: a systematic review and meta-analysis of world literature. Am J Clin Nutr. 2012 May;95(5):1113-35. doi: 10.3945/ajcn.111.030254. Epub 2012 Mar 28.

  PMID: 22456657 BACKGROUND

• Bager P, Wohlfahrt J, Westergaard T. Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy. 2008 Apr;38(4):634-42. doi: 10.1111/j.1365-2222.2008.02939.x. Epub 2008 Feb 11.

  PMID: 18266879 BACKGROUND

• Pei Z, Heinrich J, Fuertes E, Flexeder C, Hoffmann B, Lehmann I, Schaaf B, von Berg A, Koletzko S; Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus Air Pollution and Genetics (LISAplus) Study Group. Cesarean delivery and risk of childhood obesity. J Pediatr. 2014 May;164(5):1068-1073.e2. doi: 10.1016/j.jpeds.2013.12.044. Epub 2014 Feb 5.

  PMID: 24508442 BACKGROUND

• Bager P, Simonsen J, Nielsen NM, Frisch M. Cesarean section and offspring's risk of inflammatory bowel disease: a national cohort study. Inflamm Bowel Dis. 2012 May;18(5):857-62. doi: 10.1002/ibd.21805. Epub 2011 Jul 7.

  PMID: 21739532 BACKGROUND

• Garrido D, Barile D, Mills DA. A molecular basis for bifidobacterial enrichment in the infant gastrointestinal tract. Adv Nutr. 2012 May 1;3(3):415S-21S. doi: 10.3945/an.111.001586.

  PMID: 22585920 BACKGROUND

• Garrido D, Dallas DC, Mills DA. Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications. Microbiology (Reading). 2013 Apr;159(Pt 4):649-664. doi: 10.1099/mic.0.064113-0. Epub 2013 Mar 4.

  PMID: 23460033 BACKGROUND

• Garrido D, Kim JH, German JB, Raybould HE, Mills DA. Oligosaccharide binding proteins from Bifidobacterium longum subsp. infantis reveal a preference for host glycans. PLoS One. 2011 Mar 15;6(3):e17315. doi: 10.1371/journal.pone.0017315.

  PMID: 21423604 BACKGROUND

• Garrido D, Nwosu C, Ruiz-Moyano S, Aldredge D, German JB, Lebrilla CB, Mills DA. Endo-beta-N-acetylglucosaminidases from infant gut-associated bifidobacteria release complex N-glycans from human milk glycoproteins. Mol Cell Proteomics. 2012 Sep;11(9):775-85. doi: 10.1074/mcp.M112.018119. Epub 2012 Jun 27.

  PMID: 22745059 BACKGROUND

• Garrido D, Ruiz-Moyano S, Jimenez-Espinoza R, Eom HJ, Block DE, Mills DA. Utilization of galactooligosaccharides by Bifidobacterium longum subsp. infantis isolates. Food Microbiol. 2013 Apr;33(2):262-70. doi: 10.1016/j.fm.2012.10.003. Epub 2012 Oct 22.

  PMID: 23200660 BACKGROUND

• Ruiz-Moyano S, Totten SM, Garrido DA, Smilowitz JT, German JB, Lebrilla CB, Mills DA. Variation in consumption of human milk oligosaccharides by infant gut-associated strains of Bifidobacterium breve. Appl Environ Microbiol. 2013 Oct;79(19):6040-9. doi: 10.1128/AEM.01843-13. Epub 2013 Jul 26.

  PMID: 23892749 BACKGROUND

• Underwood MA, Kalanetra KM, Bokulich NA, Lewis ZT, Mirmiran M, Tancredi DJ, Mills DA. A comparison of two probiotic strains of bifidobacteria in premature infants. J Pediatr. 2013 Dec;163(6):1585-1591.e9. doi: 10.1016/j.jpeds.2013.07.017. Epub 2013 Aug 29.

  PMID: 23993139 BACKGROUND

• Underwood MA, Kalanetra KM, Bokulich NA, Mirmiran M, Barile D, Tancredi DJ, German JB, Lebrilla CB, Mills DA. Prebiotic oligosaccharides in premature infants. J Pediatr Gastroenterol Nutr. 2014 Mar;58(3):352-60. doi: 10.1097/MPG.0000000000000211.

  PMID: 24135979 BACKGROUND

• Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL. Breast milk oligosaccharides: structure-function relationships in the neonate. Annu Rev Nutr. 2014;34:143-69. doi: 10.1146/annurev-nutr-071813-105721. Epub 2014 May 15.

  PMID: 24850388 BACKGROUND

• Sela DA. Bifidobacterial utilization of human milk oligosaccharides. Int J Food Microbiol. 2011 Sep 1;149(1):58-64. doi: 10.1016/j.ijfoodmicro.2011.01.025. Epub 2011 Jan 26.

  PMID: 21342711 BACKGROUND

• Sela DA, Chapman J, Adeuya A, Kim JH, Chen F, Whitehead TR, Lapidus A, Rokhsar DS, Lebrilla CB, German JB, Price NP, Richardson PM, Mills DA. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18964-9. doi: 10.1073/pnas.0809584105. Epub 2008 Nov 24.

  PMID: 19033196 BACKGROUND

• Sela DA, Garrido D, Lerno L, Wu S, Tan K, Eom HJ, Joachimiak A, Lebrilla CB, Mills DA. Bifidobacterium longum subsp. infantis ATCC 15697 alpha-fucosidases are active on fucosylated human milk oligosaccharides. Appl Environ Microbiol. 2012 Feb;78(3):795-803. doi: 10.1128/AEM.06762-11. Epub 2011 Dec 2.

  PMID: 22138995 BACKGROUND

• Sela DA, Li Y, Lerno L, Wu S, Marcobal AM, German JB, Chen X, Lebrilla CB, Mills DA. An infant-associated bacterial commensal utilizes breast milk sialyloligosaccharides. J Biol Chem. 2011 Apr 8;286(14):11909-18. doi: 10.1074/jbc.M110.193359. Epub 2011 Feb 2.

  PMID: 21288901 BACKGROUND

• Sela DA, Mills DA. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol. 2010 Jul;18(7):298-307. doi: 10.1016/j.tim.2010.03.008. Epub 2010 Apr 19.

  PMID: 20409714 BACKGROUND

• LoCascio RG, Ninonuevo MR, Freeman SL, Sela DA, Grimm R, Lebrilla CB, Mills DA, German JB. Glycoprofiling of bifidobacterial consumption of human milk oligosaccharides demonstrates strain specific, preferential consumption of small chain glycans secreted in early human lactation. J Agric Food Chem. 2007 Oct 31;55(22):8914-9. doi: 10.1021/jf0710480. Epub 2007 Oct 5.

  PMID: 17915960 BACKGROUND

• LoCascio RG, Desai P, Sela DA, Weimer B, Mills DA. Broad conservation of milk utilization genes in Bifidobacterium longum subsp. infantis as revealed by comparative genomic hybridization. Appl Environ Microbiol. 2010 Nov;76(22):7373-81. doi: 10.1128/AEM.00675-10. Epub 2010 Aug 27.

  PMID: 20802066 BACKGROUND

• Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11971-5. doi: 10.1073/pnas.1002601107. Epub 2010 Jun 21.

  PMID: 20566857 BACKGROUND

• Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, Hamelmann E. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol. 2013 Sep;132(3):601-607.e8. doi: 10.1016/j.jaci.2013.05.043. Epub 2013 Jul 27.

  PMID: 23900058 BACKGROUND

• Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, van den Brandt PA, Stobberingh EE. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006 Aug;118(2):511-21. doi: 10.1542/peds.2005-2824.

  PMID: 16882802 BACKGROUND

• Henrick BM, Hutton AA, Palumbo MC, Casaburi G, Mitchell RD, Underwood MA, Smilowitz JT, Frese SA. Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of Bifidobacterium over the Past Century. mSphere. 2018 Mar 7;3(2):e00041-18. doi: 10.1128/mSphere.00041-18. eCollection 2018 Mar-Apr.

  PMID: 29564397 RESULT

• Casaburi et al., Colonization of breastfed infants by Bifidobacterium longum subsp. infantis EVC001 reduces virulence gene abundance

  RESULT

• Karav S, Casaburi G, Frese SA. Reduced colonic mucin degradation in breastfed infants colonized by Bifidobacterium longum subsp. infantis EVC001. FEBS Open Bio. 2018 Sep 17;8(10):1649-1657. doi: 10.1002/2211-5463.12516. eCollection 2018 Oct.

  PMID: 30338216 RESULT

• Frese SA, Hutton AA, Contreras LN, Shaw CA, Palumbo MC, Casaburi G, Xu G, Davis JCC, Lebrilla CB, Henrick BM, Freeman SL, Barile D, German JB, Mills DA, Smilowitz JT, Underwood MA. Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants. mSphere. 2017 Dec 6;2(6):e00501-17. doi: 10.1128/mSphere.00501-17. eCollection 2017 Nov-Dec.

  PMID: 29242832 RESULT

• Smilowitz JT, Moya J, Breck MA, Cook C, Fineberg A, Angkustsiri K, Underwood MA. Erratum to: Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: a phase I clinical trial. BMC Pediatr. 2017 Aug 15;17(1):180. doi: 10.1186/s12887-017-0932-7. No abstract available.

  PMID: 28810848 RESULT

• Casaburi G, Duar RM, Vance DP, Mitchell R, Contreras L, Frese SA, Smilowitz JT, Underwood MA. Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria. Antimicrob Resist Infect Control. 2019 Aug 14;8:131. doi: 10.1186/s13756-019-0583-6. eCollection 2019.

  PMID: 31423298 DERIVED

• Smilowitz JT, Moya J, Breck MA, Cook C, Fineberg A, Angkustsiri K, Underwood MA. Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: a phase I clinical trial. BMC Pediatr. 2017 May 30;17(1):133. doi: 10.1186/s12887-017-0886-9.

  PMID: 28558732 DERIVED

Related Links

• University of California, Davis Foods for Health Institute

Study Officials

• Jennifer Smilowitz, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

• Mark Underwood, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: May 29, 2015
• Study Start: November 1, 2014
• Primary Completion: July 15, 2016
• Study Completion (Estimated): June 7, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

US (1)