TABLE 3.
Included studies that examine the association between infant gut microbiome biomarkers and neurodevelopmental outcomes (N = 13)
| Author (year), country | Population context | Covariates | Study design | Final N (% male) | Biomarker(s) | Biosample age | Source | Source analytic method | Outcome measure (domains) | Age at outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Kelsey et al. (2021), USA | TD | Birthweight, income, breastfeeding, gestational age, head circumference | Cross‐sectional | 63 (58.73%) |
16S rRNA 1. Alpha diversity: Shannon Index and Chao1 2. Virulence Factors |
9–56 days post‐natal | Diaper stool via collection tube by parents | Shotgun DNA gene sequencing Database: Custom built from NCBI, incl draft/complete genomes of Bacteria, Archaea, Fungi, Viruses, Protozoa | IBQ‐R (negative emotionality; regulation/orienting; surgency/positive emotionality); FNIRS (functional brain connectivity) | 25 days |
| Aatsinki et al. (2019), Finland | TD | Sex, mode of delivery, gestational age, infant age during sampling, antibiotic treatments, breastfeeding status at 2.5 months of age | Prospective cohort | 301 (53%) |
1. 16S rRNA 2. Alpha diversity 3. Alpha richness 4. Observed species (profile, genera, OTUs): V. dispar: Enterobacteriaceae, Clostridium neonatale; Bacteroides: Bacteroides fragilis and other species; Bifidobacterium/Enterobacteriaceae, Erwinia, Streptococcus |
2.5 months postnatal | Diaper stool via collection tube by parents | 16S ribosomal RNA gene sequencing with MiSeq (Illumina) Database: GreenGenes | IBQ‐R (negative emotionality; regulation/orienting; surgency/positive emotionality) | 6 months |
| Aatsinki et al. (2022), Finland | Elevated prenatal symptoms of depression and anxiety | Maternal age and education, BMI, prenatal SSRI/SNRI use, prenatal end‐of‐pregnancy depressive symptoms, infant gestational age at birth, birth length and height, age at fecal sampling, breastfeeding status, infant antibiotics intake, mode of delivery | Secondary prospective cohort within a case–control | 131 (53%) |
16S rRNA 1. Alpha diversity 2. Observed taxa: Bifidobacterium, Clostridium |
2.5 months postnatal | Diaper stool via collection tube by parents | 16S ribosomal RNA gene sequencing with MiSeq (Illumina) Database: GreenGenes | Stimulus‐based assessment of attention to emotional faces | 8 months |
| Carlson et al. (2018), USA | TD | Breastfeeding at time of sample collection, paternal ethnicity, mode of delivery | Prospective cohort | 89 (55.1%) |
16S rRNA 1. Alpha diversity 2. Specific Taxa 3. Richness |
1 year | Diaper by parents |
16S rRNA via Illumina MiSeq Database: Not specified |
MSEL (gross motor skills; fine motor skills; visual reception; expressive and receptive language) | 1 year |
| Rozé et al. (2020), France | Preterm | Gestational age, maternal age, maternal country of birth, maternal education, birth weight Z‐score, cesarean delivery, and individual therapeutics | Cohort | 577 (52.5%) |
16S rRNA 1. Alpha diversity: Shannon Index 2. Observed taxa: Enterococcus, Staphylococcus, Escherichia, Shigella |
Median age of 23 days postbirth | Diaper stool at −80°C by researchers |
16S ribosomal RNA gene sequencing with MiSeq (Illumina) Database: RDP |
ASQ (overall neurodevelopment) | 2 years |
| Loughman et al. (2020), Australia | TD | Gestational age, mode of birth, antibiotic use during labor, breastfeeding at 4 weeks, number of siblings, household pet ownership, sex of child, age of child at time of developmental assessment | Prospective cohort | 201 (52.7%) |
16S rRNA 1. Alpha diversity 2. Beta diversity |
1, 6, and 12 months postnatal | Diaper by parents |
16S RNA via Illumina MiSeq Database: SILVA |
CBCL (internalizing problems; externalizing problems; total problems) | 2 years |
| Loughman et al. (2021), Australia | Colic | Mode of birth, sex, birth weight, gestational age, infant feeding type, infant age at baseline, antibiotic or probiotic use in 24 h prior to sample collection, baseline crying/fussing time, maternal postpartum depression at baseline and 1 month, maternal education level | Prospective cohort | 118 (53%) |
16S rRNA 1. Alpha diversity 2. Beta diversity |
7.4 weeks | Diaper by parents |
16S rRNA via Illumina MiSeq platform, using 2 × 300 bp paired‐end sequencing, Database: Not specified |
CBCL (internalizing problems; externalizing problems; total problems) | 2 years |
| Gao et al. (2019), USA | TD | Sex, maternal education, paternal age, paternal ethnicity, twin status, postnatal age at scan, income | Prospective cohort | 39 (61.5%) |
16S rRNA 1. Alpha diversity: Shannon, Chao1, Faith's Phylogenetic 2. Observed species |
1 year | Diaper by parents |
16S rRNA via Illumina MiSeq Database: Not specified |
MSEL (gross motor skills, fine motor skills; visual reception; expressive and receptive language) | 2 years |
| van den Berg et al. (2016), Netherlands | Very preterm | Gestational age, birth weight, sex, and one or more serious neonatal infections | Case–control | 79 (59.21%) | Bifidobacteria count |
48 h postnatal Preintervention 7 days 14 days postnatal |
Stool | Bacterial cells | BSID‐II/III (cognition; motor skills) | 2 years |
| Christian et al. (2015), USA | TD | Temperament characteristics, surgency/extraversion, sociability, high‐intensity pleasure and activity level, eating behavior | Prospective cohort | 77 (53.25%) |
16S rRNA 1. Alpha diversity 2. Beta diversity |
18–27 months postnatal | Diaper via collection tube by parents |
16S rRNA via Roche 454 FLX Titanium Database: GreenGenes |
ECBQ (negative affectivity; surgency/extraversion; effortful control) | 18–27 months |
| Rothenberg et al. (2021), China | Living rurally | Child had diarrhea or vomited in the previous 12 months, types of food consumed in previous 24 h, weight, height, weight‐for‐height | Cross section within a prospective cohort | 46 (55%) |
16S rRNA 1. Specific Taxa |
36 months | Sterile cotton swab by parents |
16S rRNA Illumina MiSeq 2 × 300 bp paired‐end sequencing Database: RDP |
BSID‐II (cognition; motor skills) | 36 months |
| Sordillo et al. (2019), USA | Asthma intervention | Age at ASQ‐3 assessment, cholecalciferol (vitamin D) treatment group, clinical site, mode of delivery, child's sex, and antibiotic administration in the first days of life, gestational age, maternal age, marital status, education level, family income, infant race/ethnicity, breastfeeding status 6 months after birth | Prospective cohort | 309 (55%) |
16S rRNA 1. Taxa Abundance 2. Specific Taxa |
3–6 months | Diaper via collection tube by parents |
16S rRNA via Roche 454 FLX Titanium Database: RDP |
ASQ‐3 (motor skills; problem solving; communication; social skills) | 3 years |
| Laue et al. (2020), USA | TD | Maternal self‐reported smoking during pregnancy, early exclusive breastfeeding, delivery mode, peripartum antibiotics, gestational age, age at SRS‐2, maternal education, marital status, maternal age, paternal age, and child sex | Prospective cohort | 140 (51.6%) |
16S rRNA 1. Alpha diversity: Shannon Diversity Index 2. Specific Taxa |
6 weeks, 1 year, 2 years, and 3 years postnatal | Study‐provided diaper or Receptacle tube by parents (depending on age) |
16S rRNA via Illumina MiSeq and Shotgun sequencing via Illumina NextSeq Database: GreenGenes (16S rRNA) MetaPhlAn (Shotgun) |
SRS‐2 (awareness; cognition; communication; motivation; restricted interests/repetitive behavior) | 3 years |
Abbreviations: ASQ, Ages & Stages Questionnaire; BSID‐III, Bayley Scales of Infant Development—Third Edition; CBCL, Child Behavior Checklist; ECBQ, Early Childhood Behavior Questionnaire; FNIRS, Functional Near Infrared Spectroscopy; IBQ‐R, Infant Behavior Questionnaire—Revised; MSEL, Mullen Scales of Early Learning; OTU, Operational Taxonomic Unit; SRS‐2, Social Responsiveness Scale 2; TD, typically developing.