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. 2020 May 28;12(6):1581. doi: 10.3390/nu12061581

Table 1.

Clinical trials in pediatric populations using select strains of B. infantis.

B. infantis Strain
(Manufacturer)		 Trial ID Site Enrollment Feeding Period Study Design/
Study Groups		 Study Outcomes Conclusions Year
M63
(Morinaga)		 n/a France 66 infants 1 month Term infants identified with colic a at enrollment (3 w to 3 months) multicenter double-blind randomized controlled trial (DBRCT)
  • (1)

    Standard infant formula (IF) (Control) and,

  • (2)

    IF + B. infantis M63.

  • Efficacy and safety parameters at days 15 and 30 (weight and length growth, crying duration).

  • Feeding-related GI adverse events (e.g., vomiting, constipation, regurgitation, and flatulence) were significantly lower in infant receiving M63.

 2010 [38]
ClinicalTrials.gov
NCT00920166 		France 97 infants 6 months Term infants (<postnatal day [PND] 3 at enrollment.

Multicenter DBRCT
  • (1)

    standard IF (Control), and

  • (2)

    IF + M63.


Stool samples collected at 1 and 6 months.		 Primary

  • Weight at 6 months.

Secondary

  • GI tolerance,

  • manifestation of atopic dermatitis,

  • fecal secretory IgA (SIgA),

  • fecal microbiota composition.

  • Probiotic diet was safe, well-tolerated and protective against the development of atopic dermatitis. M63 group exhibited less crying or agitation, and more quiet behavior after 1 month of feeding (p < 0.02).

 2011 [39]
n/a Italy 55 children (4–12 years old [yo]) with functional constipation. 8 weeks Prospective, placebo-controlled, randomized trial
  • (1)

    polyethylene glycol (PEG; laxative), and

  • (2)

    PEG + Probiotics: M63 + B. breve M16 + B. longum BB536.

  • Frequency of bowel movements,

  • Stool consistency according to the Bristol stool form scale,

  • presence of fecal incontinence,

  • abdominal pain,

  • painful defecation, and

  • rectal bleeding.

  • PEG with or without added probiotics was equally effective and safe in the treatment of children with chronic constipation. No difference in efficacy among the groups.

 2017 [40]
ClinicalTrials.gov
NCT02807064 		Italy 40 children (9 yo) with allergic rhinitis and asthma. 4 weeks Prospective, placebo-controlled, randomized trial
  • (1)

    probiotics: M63 + M16 + BB536, and

  • (2)

    placebo.

 Primary

  • Assessment of allergic rhinitis.

Secondary

  • Quality of life (QoL), frequency and school performance,

  • attention, and

  • evaluation of asthma exacerbations

  • Children supplemented with M63 showed a significant improvement of symptom score of allergic rhinitis and asthma.

 2017 [41]
ClinicalTrials.gov
NCT02566876 		Italy 73 children (8–16 yo) with abdominal pain (AP)-associated functional GI disorders (FGID). 6 weeks Prospective, placebo-controlled, randomized trial
  • (1)

    probiotics: M63 + M16 + BB536, and

  • (2)

    placebo

 Primary

  • Improvement of frequency and intensity of AP in children with FGID and irritable bowel syndrome (IBS).

Secondary

  • Quality of life (QoL).

  • In children with IBS, a mixture of probiotics was associated with improvement in abdominal pain and QoL.

 2017 [42]
not known Japan 44 infants (low-birthweight). 6 weeks
  • (1)

    M16

  • (2)

    probiotic mixture: M63 + M16 + BB536

  • Composition of the fecal microbiota.

  • Administration of three species of bifidobacteria resulted in earlier formation of a bifidobacteria-predominant fecal microbiota.

 2013 [43]
ATCC 15697 ClinicalTrials.gov
NCT00810160 		US 12 premature infants. 5 weeks

  • ATCC 15697

  • Bifidobacterium animalis subsp. lactis

  • Composition of the fecal microbiota.

  • ATCC 15697 was more effective at colonizing the fecal microbiota in premature infants; fecal bifidobacteria levels were significantly higher in that group.

 2013 [44]
ClinicalTrials.gov
NCT01316510 		US 24 infants with gastroschisis. 6 weeks
(or hospital discharge)
  • (1)

    ATCC 15697 (1 billion CFU twice daily) and

  • (2)

    Control (powdered elemental formula).

 Primary

  • Composition of the fecal microbiota.

Secondary

  • Length of hospital stay.

  • ATCC 15697 was well tolerated and had a moderate effect of microbiome. In infants receiving ATCC 15697 there was less dysbiosis, i.e., alterations in the microbiota associated with disease.

 2016 [45]
UCD272 (Culture Systems Inc) ClinicalTrials.gov
NCT02086110
(listed as SC268)		 US 11 children (2–11 yo) with ASD 12 weeks DBRC
  • (1)

    bovine colostrum (prebiotic) + UCD272 20 billion CFU/day, and

  • (2)

    bovine colostrum

 Primary

  • Composition of fecal microbiota.

Secondary

  • Serum immune profile.

  • Conclusions limited due to the small sample size; probiotic supplement was well tolerated. Reduction in IL-13 and TNF-α (proinflammatory cytokines) in some participants.

 2019 [46]
EVC001
(Evolve Biosystems) 		ClinicalTrials.gov
NCT02457338 		US 80 mother/
infant dyads		 21 days Randomized, parallel assignment
  • (1)

    lactation support (LS), and

  • (2)

    LS + EVC001 b


stool samples collected through PND 60.

  • Levels of B. infantis,

  • incidence of adverse events, and

  • infant weight

  • Significantly higher stool Bifidobacterium spp. in infants receiving EV0001,

  • no differences in health and safety outcomes, and

  • significantly lower daily stool frequency in EVC001 infants.

 2017 [47]

  • 16S rRNA sequencing and

  • mass spectrometry

 In infants who received EVC001:

  • significantly higher Bifidobacteriaceae and B. infantis,

  • lower stool HMO (suggesting increased metabolism by bifidobacteria),

  • lower stool pH and higher acetate and lactate, and

  • significantly higher stool B. infantis for 30 days following end of feeding period.

 2017 [36]

  • Metagenomics

  • 87.5% fewer antibiotics resistant genes (ARG) detected in the microbiome, and

  • significant reduction in abundance of Escherichia.

 2018 [48]

  • Mass spectrometry

  • Significantly less colonic mucin-derived O-glycans in stool samples from babies fed EVC001 compared to control. N-glycans (related to milk glycoproteins) increased in EVC001.

 2018
[49]

  • Immunoassay, 16S rRNA sequencing, ELISA.

  • Infants receiving EVC001 had significantly lower level of inflammatory cytokines in stool.

 2019 [50]
CECT 7210
(IM-1®,
Ordesa S.L.) 		Clinicaltrials.gov
NCT02096302 		Spain 151 term infants 12 weeks Multicenter DBRCT
  • (1)

    Standard IF (Control), and

  • (2)

    IF + CECT 7210

 Primary

  • Changes in diarrhea incidence.

Secondary

  • Changes in infections incidence, sIgA, growth, and composition of the fecal microbiota.

 In CECT 7210 group:

  • trend for decreased diarrhea reached significance at week 8, and

  • lower constipation incidence.

No differences were found in other digestive symptoms, growth, or formula intake.		 2018 [51]
BB-02 (Chr. Hansen) Australia
and New Zealand Clinical Trials Register,
ACTRN012607000144415		 Australia/New Zealand 1099 preterm infants Through hospital discharge
or term corrected age		 Multicenter DBRCT
  • (1)

    Maltodextrin (placebo), and

  • (2)

    probiotic combination: BB02, Streptococcus thermophilus Th4, and Bifidobacterium lactis BB12.

 Primary

  • At least 1 episode of definite late-onset sepsis.

Secondary

  • NEC (Bell stage 2 or more), mortality, length of hospital

  • stay, and weight at discharge.

 Incidence of NEC was significantly reduced in infants receiving the probiotic combination but not definite late-onset sepsis or mortality. 2013 [52]

  • Composition of the fecal microbiota.

 Higher levels of Bifidobacterium spp. found in infants who received the probiotics; Enterococcus reduced in infants receiving the probiotic mix during the supplementation period 2018 [53]
R0033 (Lallemand) Clinicaltrials.gov NCT02215304 Spain 221 infants 8 weeks Multicenter DBRCT
  • (1)

    Potato starch (placebo), R0033 (3 billion CFU/d), Bifidobacterium bifidum R0071, and

  • (2)

    Lactobacillus helveticus R0052.

 Primary

  • Weight, height, and head circumference.

  • Adverse events

  • Use of medication.

Secondary

  • Urine concentration of D-lactic acid,

  • changes in sleep and crying patterns, and

  • immune compounds in fecal samples.

 Use of R0033 was safe and well tolerated. No impact on growth (weight, height, and head circumference), adverse events, or serious adverse events.

Increased ratio of IL-10/IL-12 and significant reduction in Collinsella, Enterococcus, and Klebsiella genera in infants receiving R0033.		 2017 [54]




2018 [55]
135 children
(3–7 yo)		 3 months Multicenter DBRCT
  • (1)

    Synbiotic preparation (R0033, L. helveticus R0052, B. bifidum R0071, and FOS), and

  • (2)

    placebo.

 Percentage of children free of any episodes of ear, nose and throat,
respiratory tract, or gastrointestinal illness		 Synbiotic preparation decreased the risk of occurrence of common infectious diseases. No side effects were detected in either group. 2010 [56]
BT1 germanctr.de
(DRKS00003660)		 Germany 106 infants 12 months Double-blind, randomized, placebo-controlled study
  • (1)

    BT1, B. bifidum BF3, B. breve BR3, B. longum BG7 (total 10 million CFU/g), and

  • (2)

    Control

 Composition of the fecal microbiota (16s rRNA sequencing) and fecal metabolome (HPLC). Probiotic formula modulated the infant stool microbiome (e.g., Bacteroides) and metabolome (e.g., lipids) at very early stages of life, with no detectable long-term consequences. 2017 [57]

a colic defined using Wessel criteria [58]; b from postnatal day (PND) 7.