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. 2021 Jun 20;10(6):1429. doi: 10.3390/foods10061429

Table 1.

Characteristics and findings of included articles of included studies (n = 17).

Reference Study Design Population and Sample Number HMO BM Analysis Microbiota Analysis 1 Outcome Observed (Yes/No) Main Finding
Tonon et al. [15] Cross-sectional study n = 48 pairs of mothers and
C-sec and vaginally born BF infants.
Sampling at one month postpartum.		 HPLC-MS
-MSeS: Occurrence of 4 α1-2 fucosylated HMO.
  • -

    QIAamp DNA Stool Mini Kit (Qiagen)

  • -

    16S rRNA region V4 (F515/R806)

  • -

    500-cycle Miseq V2 Kit and Miseq sequencing system (Illumina)

  • -

    SILVA database

 Yes MSeS positively equates the intestinal flora of a child born vaginally or by C-sec.
Masi et al. [16] Cohort study n = 70 preterm infants (BF or FF-BF + LaBiNIC) (n = 33, NEC) Validation subset: (n = 48: n = 14, NEC). HPLC-MS
-19 most abundant HMOs.
-MSeS: presence/absence 2′FL.
  • -

    DNeasy PowerSoil Kit (Qiagen)

  • -

    Metagenomics

  • -

    HiSeq X Ten sequencing system (Illumina)

  • -

    MetaPhlan2 marker gene database

 Yes Independent of Se status, DSLNT concentration was lower in milk received by infants who showed abnormal microbiome development and developed NEC.
Borewicz et al. [17] Cohort longitudinal Study n = 24 mother–BF infant pairs. Sampling at 2, 6, and 12 weeks post-partum. PGC-UPLC-MS and HPAEC-PAD
-Total and relative abundance of 18 HMOs.
  • -

    Maxwell 16 Total RNA system (Promega) with Stool Transport and Recovery Buffer STAR (Roche)

  • -

    16S rRNA region V4 (F515/R806)

  • -

    HiSeq 2000 sequencing system (Illumina)

  • -

    SILVA database

 No Did not observe strong and consistent positive correlations between the HMOs and specific microbial OTUs, including Bifidobacterium. HMO composition is only one of many factors regulating infant gut microbial community.
Berger et al. [18] Randomized double-blinded controlled multicentric clinical trial n= 175 healthy term FF infants, (n = 87, IF with 2′FL and LNnT and n = 88, normal IF) Control: n = 38 BF infants.
Sampling at 3 months post-partum.
  • -

    QIAamp DNA Stool minikit (Qiagen), plus FastPrep apparatus and Lysing Matrix B tubes (MP Biochemicals)

  • -

    16S rRNA regions V3 and V4 (S-D-Bact-0341-b-S-17/S-D-Bact-0785-a-A-21)

  • -

    Miseq reagent kit V3 and Miseq sequencing system (Illumina)

  • -

    Ribosome Database Project and Silva database

 Yes The addition of two very specific HMOs (2′FL and LNnT) to IF shifts the microbiota toward the microbiota observed with breastfeeding, the standard in infant nutrition.
Quin et al. [19] Cohort study n = 109 mother–BF infant pairs.
Sampling at 5 months post-partum.		 CE-LIF and HPLC-MS.
-MSeS: Relative abundance 2′FL, LDFT, and LNFP1.
-16 HMOs bearing sulfate and/or phosphate groups.
-Nonsulfonated HMOs: 2′FL, LSTc, and LNP1
  • -

    QIAamp DNA Stool minikit (Qiagen).

  • -

    16S rRNA regions V3 and V4 (341F/805R)

  • -

    MiSeq sequencing system (Illumina)

  • -

    GreenGenes database.

 Yes Maternal genetics have a defining role in the establishment of early colonizers (abundance of Enterobacteriaceae was associated with MSeS), but maternal dietary intake during lactation appears to influence the community composition of the infant microbiome.
Borewicz et al. [20] Cohort study n = 121 healthy, full-term BF infants.
Sampling: At, approximately, 1 month postpartum.		 UPLC-MS
-11 neutral and five acidic HMOs) PAEC-PAD
-3′FL
  • -

    QIAamp DNA Stool minikit (Qiagen)

  • -

    16S rRNA region V4 (F515/R806)

  • -

    HiSeq sequencing system (Illumina)

  • -

    Silva database

 Yes Statistically significant associations between infant fecal microbiota composition and LNFPI and 2′FL levels. Degradation of specific HMOs could be correlated with an increase in relative abundance of various phylotypes within the genus Bifidobacterium and to a lesser extent within the genera Bacteroides and Lactobacillus.
Paganini et al. [21] Double-masked randomized controlled trial study. Cross-sectional study. n = 80 mother–infant pairs, BF + supplement or not Sampling at baseline of clinical trial, after 3 weeks and after 4 months. HPAE-PAD
-MSeS: presence/absence 2′FL and LNFPI
- Total fucosylated sum of 2′FL, 3′FL, LNFPI, LNFPII, and LNFPIII; total sialylated sum of 6′SL, 3′SL, LSTd, LSTa, DSLNT and total non-fucosylated and non-sialylated sum of LNnT, LNT, and LNnH.
  • -

    Maxwell 16 Tissue LEV Total RNA Purification Kit (Promega)

  • -

    16S rRNA region V3–V4 (357F/802R)

  • -

    MiSeq sequencing system (Illumina)

  • -

    GreenGenes database

 No MSeS does not have a major impact on the gut microbiota of the mothers with the exception of a higher abundance of C. perfringens among Se- compared to Se mothers.
Bai et al. [22] Longitud Cohort study n = 56 mother–vaginally born BF pairs.
Sampling at days 6, 42, 120, and 180 post-birth.		 LC-QTOF-MS
-MSeS: presence/absence LDFT and LNFP I
  • -

    E.Z.N.A. stool DNA kit (Omega Bio-tek)

  • -

    16S rRNA region V4 (520F/802R)

  • -

    IlluminaGAIIx platform (Illumina)

  • -

    NCBI NR database

 Yes Bifidobacterial established earlier (and in higher amounts in Se+-fed infants). The relative abundances of this genus continued to increase more than 180 days of lactation in the Se+ group.
Korpela et al. [23] Cohort study n = 76 mothers–C-sec and vaginally born BF infants.
Sampling: BM on day 3 and feces at 3 months.		 HPLC-MALDI-TOF and HPAEC
-MSeS: 2′FL quantification.
  • -

    Repeated Bead Beating protocol and QIAamp DNA Stool Mini Kit columns (Qiagen)

  • -

    16S rRNA region V3–V4 (N.S.)

  • -

    MiSeq sequencing system (Illumina)

  • -

    SILVA database

 Yes The C-sec born infants of Se+ mothers had a more modest deviation in microbiota composition, compared to those of Se- mothers.
Davis et al. [24] Longitudinal sub-study embedded within a randomized trial. n = 33 mother–BF infant pairs.
Sampling: At 4, 16, and 20 weeks postpartum.		 HPLC-TOF.
MSeS: α 1-2 fucosylated
HMO quantification of 2′ FL, LDFT, TFLNH, DFLNHa, DFLNHc, and IFLNH I.
  • -

    Zymo ZR Fecal DNA MiniPrep™ Isolation Kit

  • -

    16S rRNA V4 region (F515/R806)

  • -

    MiSeq 2000 sequencing system (Illumina)

  • -

    Database not specified

 Yes The microbiome’s ability to break down certain types of oligosaccharides depends on the specific strains that make up the baby’s microbiota. These strains’ variability may contribute to their inability to find functional differences in microbiomes between babies fed by mothers of different secretor status.
Underwood et al. [25] Cohort study n = 29 preterm BF infants supplemented with B. breve, strain M16-V.
Sampling: close to the probiotic start and 3 weeks later.		 Nano-HPLC-chip/TOF-MS
-MSeS: α(1,2) fucosylated HMOs abundance >6%.
  • -

    QIAGEN Stool Mini Kit

  • -

    16S rRNA region V4 (F515/R806)

  • -

    MiSeq sequencing system (Illumina)

  • -

    GreenGenes database

 No MSeS was not a significant predictor of response to the administered probiotic B. breve.
Matsuki et al. [26] Randomized, double-blind, placebo-controlled trial n = 35 FF infants (supplemented with GOS (OM55N).
Sampling at the start of the trial and 2 weeks later.
  • -

    FastPrep FP 120 instrument and phenol/chloroform/isoamyl alcohol extraction

  • -

    16S rRNA V1–V2 regions (66F-TAG-linker A/338Rm-linker B)

  • -

    454 GS Junior platform (Roche)

  • -

    Ribosomal Database Project

 Yes The formula supplementation with GOS (OM55N) stimulated the growth of bifidobacteria and resulted in reduced α-diversity of the gut microbiota.
Smith-Brown et al. [27] Cohort study n = 37 BF children 2 years old and 17 eligible mothers (20 excluded due to pregnancy within the previous 12 months) MSeS was determined from blood and saliva samples using hemagglutination inhibition technique.
  • -

    Bead beating and Maxwell 16 Tissue DNA Purification Kit (Promega)

  • -

    16S rRNA region V6–V8 (1406F/1525R)

  • -

    MiSeq sequencing system (Illumina)

  • -

    GreenGenes database

 Yes Bifidobacterium was increased in the BF children of Se+ mothers compared to Se- mothers.
Lewis et al. [28] Longitudinal cohort study n = 44 mother–BF infant pairs
Sampling: At day 6, 21, 71, and/or 120 postpartum.		 Nano-HPLC-chip-TOF-MS.
-MSeS: α(1,2) fucosylated HMOs abundance.
  • -

    ZR Fecal DNA MiniPrep kit (ZYMO)

  • -

    16S rRNA region V4 (F515/R806)

  • -

    MiSeq sequencing system (Illumina)

  • -

    Ribosomal Database Project

 Yes Se+ fed infants generally had higher relative amounts of Bifidobacterium and Bacteroides and lower levels of enterobacteria, clostridia, and streptococci.
De Leoz et al. [29] Longitudinal Proof-of-concept study n = 2 infants (A: BF; B: formula supplementation
4 days and then was solely BF)
Sampling: twice/week first month, twice/month
second month, and once or twice/month thereafter.		 Nano-HPLC-Chip/TOF MS
-HMO profile and HMO quantitation to the isomer level (fecal samples).
  • -

    QIAmp DNA Stool Mini Kit (Qiagen)

  • -

    16S rRNA regions V1–V3 and V4 (B-8F/A-518R and F515/R806)

  • -

    Genome Sequencer GS-FLX (Roche) and Genome Analyzer II sequencing system (Illumina)

  • -

    Ribosomal Database Project

 Yes Fecal HMO profiles correlated with changes in bacterial population. Positive and negative correlations between the fecal isomers of HMO and the relative abundance of bacterial taxa were found at the order level.
Wang et al. [30] Quasi-experimental cohort study n = 22
mother–infant pairs. (16 BF and 6 FF)
Sampling: At 3 months post-partum.		 HPLC-Chip/TOF-MS
-Until 141 HMOs/sample.
  • -

    QIAgen DNA Mini Stool Kit (Qiagen)

  • -

    16S rRNA region V1-V3 (27F-DegS/534R)

  • -

    454 Life Sciences Genome Sequencer FLX (Roche)

  • -

    Ribosomal Database Project

 Yes The microbial composition of BF infants is correlated with the presence of HMO in their mother′s milk.
Coppa et al. [31] Cohort study n = 256
mother–infant pairs.
Sampling: At 30 days post-partum.		 HPAEC
-18 HMOs.
-4 BM groups on the basis of the presence or the absence of 2′FL and LNFPII.
  • -

    Phenol/chloroform extraction

  • -

    PCR-DGGE (B. adolescentis, B. catenulatum, B. infantis, B. longum, B. breve, and B. bifidum primers)

  • -

    PCR fragment sequencing

  • -

    Ribosomal Database Project

 Yes No substantial differences in bifidobacteria species composition within infants fed with groups 1, 2, and 3 BM; with group 4 BM (with slight quantity of fucosyloligosaccharides), the microbiota was characterized by a greater frequency of B. adolescentis and the absence of B. catenulatum and harbored a different intestinal microbiota.

Breastfed (BF); Infant Formula (IF); Formula-fed (FF); Cesarean section (C-sec); Necrotizing enterocolitis (NEC); Operational taxonomic units (OTUs); Breastmilk (BM); Maternal secretor status (MSeS); Porous graphitized carbon-ultra high-performance liquid chromatography–mass spectrometry (PGC-UPLC-MS); High-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD); Capillary electrophoresis with laser-induced fluorescence (CE-LIF); High-performance anion exchange chromatography–pulsed amperometric detection (HPAEC-PAD); Matrix-assisted laser desorption/ionization–time of fight mass spectrometry (MALDI-TOF-MS); Bifidobacterium-specific terminal restriction fragment length polymorphism assay (Bif-TRFLP); LaBiNIC (L. acidophilus, B. infantis, and B. bifidum) or Infloran (L. acidophilus and B. Bifidum).1 Including the following information: DNA extraction kit, 16S rRNA gene hypervariable region (primers), sequencing system, rRNA database. N.S.: not specified.