Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: A phase I clinical trial

Jennifer T. Smilowitz, Jackelyn Moya, Melissa A. Breck, Chelsea Cook, Annette Fineberg, Kathleen Angkustsiri, Mark Underwood

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Historically, bifidobacteria were the dominant intestinal bacteria in breastfed infants. Still abundant in infants in developing nations, levels of intestinal bifidobacteria are low among infants in developed nations. Recent studies have described an intimate relationship between human milk and a specific subspecies of Bifidobacterium, B. longum subsp. infantis (B. infantis), yet supplementation of breastfed, healthy, term infants with this organism, has not been reported. The IMPRINT Study, a Phase I clinical trial, was initiated to determine the safety and tolerability of supplementing breastfed infants with B. infantis (EVC001). Methods: Eighty mother-infant dyads were enrolled in either lactation support plus B. infantis supplementation (BiLS) or lactation support alone (LS). Starting with Day 7 postnatal, BiLS infants were fed 1.8-2.8 × 1010 CFU B. infantis EVC001 daily in breast milk for 21 days. Mothers collected fecal samples, filled out health questionnaires, and kept daily logs about their infants' feeding and gastrointestinal symptoms from birth until Day 61 postnatal. Safety and tolerability were determined from maternal reports. Results: There were no differences in the mean gestational age at birth, weight 1 and 2 months postnatal, and breast milk intake between groups. The mean Log10 change in fecal Bifidobacterium from Day 6 to Day 28 was higher (p = 0.0002) for BiLS (6.6 ± 2.8 SD) than for LS infants (3.5 ± 3.5 SD). Daily stool number was higher (p < 0.005) for LS and lower (p < 0.05) for BiLS infants during supplementation than at Baseline. During supplementation, watery stools decreased and soft stools increased by 36% over baseline in BiLS infants (p < 0.05) with no significant changes in stool consistency for the LS infants. None of the safety and tolerability endpoints, including flatulence, bloody stool, body temperature, ratings of gastrointestinal symptoms, use of antibiotics or gas-relieving medications, infant colic, jaundice, number of illnesses, sick doctor visits, or diagnoses of eczema were different for the groups at any point. Conclusions: The B. infantis EVC001 supplement was safely consumed and well-tolerated. Stools were fewer and better formed in infants in the BiLS group compared with LS group. Adverse events were those expected in healthy infants and not different between groups. Trial registration: ClinicalTrials.gov NCT02457338. Registered May 27, 2015.

Original languageEnglish (US)
Article number133
JournalBMC Pediatrics
Volume17
Issue number1
DOIs
StatePublished - May 30 2017

Fingerprint

Clinical Trials, Phase I
Safety
Lactation
Bifidobacterium
Human Milk
Mothers
Bifidobacterium longum subspecies infantis
Flatulence
Colic
Eczema
Jaundice
Body Temperature
Developed Countries
Birth Weight

Keywords

  • Bifidobacterium longum subspecies infantis
  • Breast milk
  • Gut microbiome
  • Human milk oligosaccharides
  • Infant
  • Probiotics
  • Supplementation
  • Tolerability

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants : A phase I clinical trial. / Smilowitz, Jennifer T.; Moya, Jackelyn; Breck, Melissa A.; Cook, Chelsea; Fineberg, Annette; Angkustsiri, Kathleen; Underwood, Mark.

In: BMC Pediatrics, Vol. 17, No. 1, 133, 30.05.2017.

Research output: Contribution to journalArticle

@article{d0066767ef334c558cb3077d712c7fc2,
title = "Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: A phase I clinical trial",
abstract = "Background: Historically, bifidobacteria were the dominant intestinal bacteria in breastfed infants. Still abundant in infants in developing nations, levels of intestinal bifidobacteria are low among infants in developed nations. Recent studies have described an intimate relationship between human milk and a specific subspecies of Bifidobacterium, B. longum subsp. infantis (B. infantis), yet supplementation of breastfed, healthy, term infants with this organism, has not been reported. The IMPRINT Study, a Phase I clinical trial, was initiated to determine the safety and tolerability of supplementing breastfed infants with B. infantis (EVC001). Methods: Eighty mother-infant dyads were enrolled in either lactation support plus B. infantis supplementation (BiLS) or lactation support alone (LS). Starting with Day 7 postnatal, BiLS infants were fed 1.8-2.8 × 1010 CFU B. infantis EVC001 daily in breast milk for 21 days. Mothers collected fecal samples, filled out health questionnaires, and kept daily logs about their infants' feeding and gastrointestinal symptoms from birth until Day 61 postnatal. Safety and tolerability were determined from maternal reports. Results: There were no differences in the mean gestational age at birth, weight 1 and 2 months postnatal, and breast milk intake between groups. The mean Log10 change in fecal Bifidobacterium from Day 6 to Day 28 was higher (p = 0.0002) for BiLS (6.6 ± 2.8 SD) than for LS infants (3.5 ± 3.5 SD). Daily stool number was higher (p < 0.005) for LS and lower (p < 0.05) for BiLS infants during supplementation than at Baseline. During supplementation, watery stools decreased and soft stools increased by 36{\%} over baseline in BiLS infants (p < 0.05) with no significant changes in stool consistency for the LS infants. None of the safety and tolerability endpoints, including flatulence, bloody stool, body temperature, ratings of gastrointestinal symptoms, use of antibiotics or gas-relieving medications, infant colic, jaundice, number of illnesses, sick doctor visits, or diagnoses of eczema were different for the groups at any point. Conclusions: The B. infantis EVC001 supplement was safely consumed and well-tolerated. Stools were fewer and better formed in infants in the BiLS group compared with LS group. Adverse events were those expected in healthy infants and not different between groups. Trial registration: ClinicalTrials.gov NCT02457338. Registered May 27, 2015.",
keywords = "Bifidobacterium longum subspecies infantis, Breast milk, Gut microbiome, Human milk oligosaccharides, Infant, Probiotics, Supplementation, Tolerability",
author = "Smilowitz, {Jennifer T.} and Jackelyn Moya and Breck, {Melissa A.} and Chelsea Cook and Annette Fineberg and Kathleen Angkustsiri and Mark Underwood",
year = "2017",
month = "5",
day = "30",
doi = "10.1186/s12887-017-0886-9",
language = "English (US)",
volume = "17",
journal = "BMC Pediatrics",
issn = "1471-2431",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants

T2 - A phase I clinical trial

AU - Smilowitz, Jennifer T.

AU - Moya, Jackelyn

AU - Breck, Melissa A.

AU - Cook, Chelsea

AU - Fineberg, Annette

AU - Angkustsiri, Kathleen

AU - Underwood, Mark

PY - 2017/5/30

Y1 - 2017/5/30

N2 - Background: Historically, bifidobacteria were the dominant intestinal bacteria in breastfed infants. Still abundant in infants in developing nations, levels of intestinal bifidobacteria are low among infants in developed nations. Recent studies have described an intimate relationship between human milk and a specific subspecies of Bifidobacterium, B. longum subsp. infantis (B. infantis), yet supplementation of breastfed, healthy, term infants with this organism, has not been reported. The IMPRINT Study, a Phase I clinical trial, was initiated to determine the safety and tolerability of supplementing breastfed infants with B. infantis (EVC001). Methods: Eighty mother-infant dyads were enrolled in either lactation support plus B. infantis supplementation (BiLS) or lactation support alone (LS). Starting with Day 7 postnatal, BiLS infants were fed 1.8-2.8 × 1010 CFU B. infantis EVC001 daily in breast milk for 21 days. Mothers collected fecal samples, filled out health questionnaires, and kept daily logs about their infants' feeding and gastrointestinal symptoms from birth until Day 61 postnatal. Safety and tolerability were determined from maternal reports. Results: There were no differences in the mean gestational age at birth, weight 1 and 2 months postnatal, and breast milk intake between groups. The mean Log10 change in fecal Bifidobacterium from Day 6 to Day 28 was higher (p = 0.0002) for BiLS (6.6 ± 2.8 SD) than for LS infants (3.5 ± 3.5 SD). Daily stool number was higher (p < 0.005) for LS and lower (p < 0.05) for BiLS infants during supplementation than at Baseline. During supplementation, watery stools decreased and soft stools increased by 36% over baseline in BiLS infants (p < 0.05) with no significant changes in stool consistency for the LS infants. None of the safety and tolerability endpoints, including flatulence, bloody stool, body temperature, ratings of gastrointestinal symptoms, use of antibiotics or gas-relieving medications, infant colic, jaundice, number of illnesses, sick doctor visits, or diagnoses of eczema were different for the groups at any point. Conclusions: The B. infantis EVC001 supplement was safely consumed and well-tolerated. Stools were fewer and better formed in infants in the BiLS group compared with LS group. Adverse events were those expected in healthy infants and not different between groups. Trial registration: ClinicalTrials.gov NCT02457338. Registered May 27, 2015.

AB - Background: Historically, bifidobacteria were the dominant intestinal bacteria in breastfed infants. Still abundant in infants in developing nations, levels of intestinal bifidobacteria are low among infants in developed nations. Recent studies have described an intimate relationship between human milk and a specific subspecies of Bifidobacterium, B. longum subsp. infantis (B. infantis), yet supplementation of breastfed, healthy, term infants with this organism, has not been reported. The IMPRINT Study, a Phase I clinical trial, was initiated to determine the safety and tolerability of supplementing breastfed infants with B. infantis (EVC001). Methods: Eighty mother-infant dyads were enrolled in either lactation support plus B. infantis supplementation (BiLS) or lactation support alone (LS). Starting with Day 7 postnatal, BiLS infants were fed 1.8-2.8 × 1010 CFU B. infantis EVC001 daily in breast milk for 21 days. Mothers collected fecal samples, filled out health questionnaires, and kept daily logs about their infants' feeding and gastrointestinal symptoms from birth until Day 61 postnatal. Safety and tolerability were determined from maternal reports. Results: There were no differences in the mean gestational age at birth, weight 1 and 2 months postnatal, and breast milk intake between groups. The mean Log10 change in fecal Bifidobacterium from Day 6 to Day 28 was higher (p = 0.0002) for BiLS (6.6 ± 2.8 SD) than for LS infants (3.5 ± 3.5 SD). Daily stool number was higher (p < 0.005) for LS and lower (p < 0.05) for BiLS infants during supplementation than at Baseline. During supplementation, watery stools decreased and soft stools increased by 36% over baseline in BiLS infants (p < 0.05) with no significant changes in stool consistency for the LS infants. None of the safety and tolerability endpoints, including flatulence, bloody stool, body temperature, ratings of gastrointestinal symptoms, use of antibiotics or gas-relieving medications, infant colic, jaundice, number of illnesses, sick doctor visits, or diagnoses of eczema were different for the groups at any point. Conclusions: The B. infantis EVC001 supplement was safely consumed and well-tolerated. Stools were fewer and better formed in infants in the BiLS group compared with LS group. Adverse events were those expected in healthy infants and not different between groups. Trial registration: ClinicalTrials.gov NCT02457338. Registered May 27, 2015.

KW - Bifidobacterium longum subspecies infantis

KW - Breast milk

KW - Gut microbiome

KW - Human milk oligosaccharides

KW - Infant

KW - Probiotics

KW - Supplementation

KW - Tolerability

UR - http://www.scopus.com/inward/record.url?scp=85019698471&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019698471&partnerID=8YFLogxK

U2 - 10.1186/s12887-017-0886-9

DO - 10.1186/s12887-017-0886-9

M3 - Article

C2 - 28558732

AN - SCOPUS:85019698471

VL - 17

JO - BMC Pediatrics

JF - BMC Pediatrics

SN - 1471-2431

IS - 1

M1 - 133

ER -