Research ArticleHIV

Maternal HIV infection influences the microbiome of HIV-uninfected infants

See allHide authors and affiliations

Science Translational Medicine  27 Jul 2016:
Vol. 8, Issue 349, pp. 349ra100
DOI: 10.1126/scitranslmed.aaf5103
  • Fig. 1. Microbiomes of 50 mother-infant dyads.

    There were differences in the microbiomes based on the site of sample collection. (A) PCoA of unweighted UniFrac distances revealed that each sample type clustered into distinct groups. (B) α-Diversity (Shannon index) was similar for all sample sites except for the vagina, which was significantly less diverse than other sample sites (P = 0.021). (C) Bacterial compositions across sample sites (mother: areolar skin, breast milk, and vagina; infant: mouth, skin, and stool) at the taxonomic level of family. (D) Heat map representation of individual bacterial compositions at the family level. Families with an overall relative abundance of less than 0.5% are omitted for the sake of clarity.

  • Fig. 2. Minimal effects of HIV infection on maternal microbiomes.

    (A) PCoA of unweighted UniFrac distances based on the mother’s HIV status at each sample site (areolar skin, breast milk, and vagina). (B) α-Diversity (Shannon index) at each sample site based on the mother’s HIV status. (C) Bacterial compositions across sample sites at the taxonomic level of family. (D) Heat map representation of individual bacterial compositions at the family level. Families with an overall relative abundance of less than 0.5% are omitted for the sake of clarity. (E) List of all taxa at any level or sample site that were significantly different based on the mother’s HIV status using corrected P values (FDR P < 0.1).

  • Fig. 3. Effects of maternal HIV infection on the infant microbiome.

    (A) PCoA of unweighted UniFrac distances based on the mother’s HIV status at each infant sample site (mouth, skin, and stool). (B) α-Diversity (Shannon index) at each infant sample site based on the mother’s HIV status. (C) Bacterial compositions across infant sample sites at the taxonomic level of family. (D) Heat map representation of individual bacterial compositions at the family level. Families with an overall relative abundance of less than 0.5% are omitted for the sake of clarity. (E) List of all taxa at any family level or infant sample site that were significantly different based on the mother’s HIV status using corrected P values (FDR P < 0.1).

  • Fig. 4. Microbiome dysbiosis in HIV-exposed, uninfected infants.

    (A) Random forest classification scheme to identify taxa associated with HIV status. Bacterial taxa enriched in HIV-unexposed infants are represented on the left, and bacterial taxa enriched in HIV-exposed uninfected infants are on the right. (B) Bayesian estimate of the proportion of microbes in the infant samples that came from the mother. (C) A relative maturity index was calculated for each experimental sample based on the relative stool microbiome age versus the age of the subject at collection. This was then plotted along with the normalized midline of the previously published reference cohort of healthy controls.

  • Fig. 5. HMO composition and the infant stool microbiome.

    (A) The HMO composition of breast milk based on maternal HIV status. Unadjusted P values that are ≤0.1 are shown. (B) Significant associations between specific HMOs and bacterial families. Blue bars represent HIV-unexposed infants. Red bars represent HIV-exposed, uninfected infants. Spearman correlation coefficients are plotted along the x axis. (C) The infant’s stool relative maturity compared to the HMO composition of mother’s breast milk using Spearman correlations. The two HMOs with FDR P values of <0.1 (LNT and 3FL) are shown. 2′FL, 2′-fucosyllactose; 3FL, 3-fucosyllactose; LNnT, lacto-N-neotetraose; 3′SL, 3′-sialyllactose; LNT, lacto-N-tetraose; LNFP-1, lacto-N- fucopentaose 1; LNFP-2, lacto-N- fucopentaose 2; LNFP-3, lacto-N- fucopentaose 3; LSTb, sialyllacto-N-tetraose b; LSTc, sialyllacto-N-tetraose c; DFLNT, difucosialyllacto-N-tetraose; DSLNT, disialyllacto-N-tetraose; FLNH, fucosyllacto-N-hexaose; DFLNH, difucosyllacto-N-hexaose; FDSLNH, fucosyl-disialyllacto-N-hexaose; DSLNH, disialyllacto-N-hexaose.

  • Table 1. Demographic and clinical characteristics of 50 mothers from Port-au-Prince, Haiti.

    Half of the mothers were HIV-infected.

    Maternal characteristicsHIV+ mothers (n = 25)HIV mothers (n = 25)P
    Maternal age (years)
      Mean (SD)30.2 (5.3)27.1 (7.5)
      Median (IQR)31 (28–34)27 (20–31)0.06
    Use of antibiotics during pregnancy or postpartum period (%)18 (72)10 (40)0.02
    Vaginal delivery (%)19 (76)24 (96)0.10
    Delivery at home (%)10 (42)11 (44)0.87
    Term delivery (%)23 (92)22 (88)0.64
    BMI (kg/m2)
      Mean (SD)24.7 (4.2)21.9 (2.8)
      Median (IQR)25.3 (21.1–27.5)21.4 (20.3–23.4)0.023
    Maternal mid-upper arm circumference (cm)
      Mean (SD)25.6 (5.5)26.0 (4.0)
      Median (IQR)27 (23–29.0)26 (24–28)0.59
    Exclusive breastfeeding (%)20 (80)19 (76)0.73
    Breast problems: cracked nipples, clogged ducts, and mastitis (%)10 (40)9 (36)0.77
  • Table 2. Clinical characteristics of 25 HIV-positive mothers from Port-au-Prince, Haiti.

    All 25 mothers were on combination antiretroviral therapy.

    Clinical characteristics of HIV+ mothersn = 25
    Viral load (copies/ml)
      Median (IQR)Undetectable (Undetectable to 3300)
    Viral load (%)
      Undetectable17 (68)
      Detectable8 (32)
    CD4 T cell count (cells/mm3)
      Mean (SD)553 (289)
      Median (IQR)567 (369 to 681)
    CD4 T cell count <350 (%)
      >35020 (80)
      1–3505 (20)
    On antiretroviral therapy (%)25 (100)
  • Table 3. Demographic and clinical characteristics of 50 infants from Port-au-Prince, Haiti.

    Half of the infants were HIV-exposed (born to HIV-positive mothers). None of the infants received courses of antibiotics. Only one infant subsequently acquired HIV infection. This mother-infant dyad was excluded from subsequent analyses. N/A, not applicable.

    Infant characteristicsHIV-exposed (n = 25)HIV-unexposed (n = 25)P
    Infant age (days)
      Mean (SD)66.6 (44.8)71.4 (56.6)0.65
      Median (IQR)48 (33 to 113)72 (16 to 96)
    Female sex (%)13 (52)13 (52)1.00
    Antibiotics (%)0 (0)0 (0)1.00
    Weight-for-age z score
      Mean (SD)−0.9 (1.2)−1.0 (1.3)0.90
      Median (IQR)−1.2 (−1.6 to −0.4)−0.8 (−1.6 to 0.1)
    Weight-for-age z score (%)
      <−1.57 (28)8 (32)0.76
      ≥−1.518 (72)17 (68)
    Length/height-for-age z score
      Mean (SD)−1.2 (1.6)−0.6 (1.7)0.25
      Median (IQR)−1.4 (−1.8 to 0.0)−0.1 (−1.0 to 0.5)
    Length/height-for-age z score (%)
      <−1.512 (48)5 (20)0.037
      ≥−1.513 (52)20 (80)
    HIV infection (%)1 (4)N/A

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/8/349/349ra100/DC1

    Fig. S1. Sample analysis based on individual, site, and mother-infant pairs.

    Fig. S2. Further stratification of the infant gut bacterial diversity by maternal CD4 T cell count and maternal HIV viral load.

    Table S1. α-Diversity values based on the mother’s HIV status.

    Table S2. Unadjusted relative abundance percentages.

    Table S3. PERMANOVA based on distance matrices.

    Table S4. Comparison of the 33 age-discriminatory taxa based on maternal HIV status.

    Table S5. Evaluation of infant stool and skin microbial pathways based on maternal HIV status using PICRUSt analysis.

  • Supplementary Material for:

    Maternal HIV infection influences the microbiome of HIV-uninfected infants

    Jeffrey M. Bender, Fan Li, Shoria Martelly, Erin Byrt, Vanessa Rouzier, Marguerithe Leo, Nicole Tobin, Pia S. Pannaraj, Helty Adisetiyo, Adrienne Rollie, Chintda Santiskulvong, Shuang Wang, Chloe Autran, Lars Bode, Daniel Fitzgerald, Louise Kuhn, Grace M. Aldrovandi*

    *Corresponding author. Email: gracea{at}mac.com

    Published 27 July 2016, Sci. Transl. Med. 8, 349ra100 (2016)
    DOI: 10.1126/scitranslmed.aaf5103

    This PDF file includes:

    • Fig. S1. Sample analysis based on individual, site, and mother-infant pairs.
    • Fig. S2. Further stratification of the infant gut bacterial diversity by maternal CD4 T cell count and maternal HIV viral load.
    • Table S1. α-Diversity values based on the mother’s HIV status.
    • Table S2. Unadjusted relative abundance percentages.
    • Table S3. PERMANOVA based on distance matrices.
    • Table S4. Comparison of the 33 age-discriminatory taxa based on maternal HIV status.
    • Table S5. Evaluation of infant stool and skin microbial pathways based on maternal HIV status using PICRUSt analysis.

    [Download PDF]

Navigate This Article