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| Name | Class |
|---|---|
| Evolve BioSystems, Inc. | INDUSTRY |
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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.
The purpose of this clinical trial is to determine the effects of supplementing the probiotic Bifidobacterium longum subsp. infantis for the first 21 days of life in healthy term breastfed infants delivered via C-section or vaginal delivery on gut bacteria composition during, 1 week, and 1 month after supplementation compared with matched-control term infants receiving standard care. The investigators' specific aim is to compare the fecal microbiota (total B. infantis, total Bifidobacterium, total bacteria and composition of microbiota) between the supplement and control groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Supplement Group | Experimental | This group will receive probiotic B. infantis supplementation, plus standard care and lactation consultation. |
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| Control Group | No Intervention | This group will receive standard care plus lactation consultation only. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bifidobacterium | Dietary Supplement |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Infant fecal bacteria oligosaccharide consumption | Compare the oligosaccharides in human milk against the oligosaccharides in infant feces before, during, and after B. infantis supplementation by using liquid chromatography Chip-TOP mass spectrometry. | days 7, 14, 21, 32, 60 |
| Infant fecal sialic acid concentrations |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer Smilowitz, PhD | University of California, Davis | Principal Investigator |
| Mark Underwood, MD | University of California, Davis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Davis Medical Center | Sacramento | California | 95817 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22456657 | Background | 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. | |
| 18266879 | 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. |
| Label | URL |
|---|---|
| University of California, Davis Foods for Health Institute | View source |
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| Months 4, 6, 8, 10, 12, 18 and 24 |
Measure the change in infant fecal sialic acid concentrations before, during, and after B. infantis supplementation in infant stool samples using enzymatic assay. |
| baseline, days 10, 14, 17, 21, 25, 29, 32, 40, 50, 60 |
| Maternal fecal B. infantis, Bifidobacterium, total bacteria, and microbiota composition | Compare the maternal fecal B. infantis, bifidobacterium, total bacteria, and microbiota composition with changes in infant fecal microbiota | baseline, day 60 |
| Infant weight | Determine the change in weight across the study duration using a digital infant scale and change in gut microbiota | birth, hospital discharge, days 15, 33, 61 |
| Fecal inflammatory mediators | Compare GI function between infants in the B. infantis and control groups through the measurement of fecal inflammatory mediators. | Baseline-days 60 |
| Fecal gut barrier function barrier markers | Compare GI function between infants in the B. infantis and control groups through the measurement of GI barrier function markers. | Baseline-days 60 |
| Fecal lipopolysaccharide | Compare GI function between infants in the B. infantis and control groups through the measurement of fecal lipopolysaccharide binding. | Baseline-days 60 |
| Fecal short-chain fatty acids | Determine the relationship between fecal microbiota composition and fecal short chain fatty acids | Baseline-days 60 |
| Fecal microbiome-Follow-up | next generation sequencing | Months 4, 6, 8, 10, 12 |
| Fecal B. infantis-Follow-up | Q Polymerase Chain Reaction (PCR) | Months 4, 6, 8, 10, 12 |
| Fecal Bifidobacterium-Follow-up | Q PCR | Months 4, 6, 8, 10, 12 |
| 24508442 | 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. |
| 21739532 | 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. |
| 22585920 | 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. |
| 23460033 | 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. |
| 21423604 | 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. |
| 22745059 | 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. |
| 23200660 | 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. |
| 23892749 | 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. |
| 23993139 | 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. |
| 24135979 | 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. |
| 24850388 | 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. |
| 21342711 | 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. |
| 19033196 | 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. |
| 22138995 | 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. |
| 21288901 | 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. |
| 20409714 | 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. |
| 17915960 | 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. |
| 20802066 | 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. |
| 20566857 | 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. |
| 23900058 | 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. |
| 16882802 | 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. |
| 29564397 | Result | 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. |
| Result | Casaburi et al., Colonization of breastfed infants by Bifidobacterium longum subsp. infantis EVC001 reduces virulence gene abundance |
| 30338216 | 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. |
| 29242832 | 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. |
| 28810848 | 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. |
| 31423298 | Derived | 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. |
| 28558732 | 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. |