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. 2018 Mar 6;3(3):e00140-17.
doi: 10.1128/mSystems.00140-17. eCollection 2018 May-Jun.

Development of the Human Mycobiome over the First Month of Life and across Body Sites

Affiliations

Development of the Human Mycobiome over the First Month of Life and across Body Sites

Tonya L Ward et al. mSystems. .

Abstract

With the advent of next-generation sequencing and microbial community characterization, we are beginning to understand the key factors that shape early-life microbial colonization and associated health outcomes. Studies characterizing infant microbial colonization have focused mostly on bacteria in the microbiome and have largely neglected fungi (the mycobiome), despite their relevance to mucosal infections in healthy infants. In this pilot study, we characterized the skin, oral, and anal mycobiomes of infants over the first month of life (n = 17) and the anal and vaginal mycobiomes of mothers (n = 16) by internal transcribed spacer 2 (ITS2) amplicon sequencing. We found that infant mycobiomes differed by body site, with the infant mycobiomes at the anal sites being different from those at the skin and oral sites. The relative abundances of body site-specific taxa differed by birth mode, with significantly more Candida albicans fungi present on the skin of vaginally born infants on day 30 and significantly more Candida orthopsilosis fungi present in the oral cavity of caesarean section-born infants throughout the first month of life. We found the mycobiomes within individual infants to be variable over the first month of life, and vaginal birth did not result in infant mycobiomes that were more similar to the mother's vaginal mycobiome. Therefore, although vertical transmission of specific fungal isolates from mother to infant has been reported, it is likely that other sources (environment, other caregivers) also contribute to early-life mycobiome establishment. Thus, future longitudinal studies of mycobiome and bacterial microbiome codevelopment, with dense sampling from birth to beyond the first month of life, are warranted. IMPORTANCE Humans are colonized by diverse fungi (mycobiome), which have received much less study to date than colonizing bacteria. We know very little about the succession of fungal colonization in early life and whether it may relate to long-term health. To better understand fungal colonization and its sources, we studied the skin, oral, and anal mycobiomes of healthy term infants and the vaginal and anal mycobiomes of their mothers. Generally, infants were colonized by few fungal taxa, and fungal alpha diversity did not increase over the first month of life. There was no clear community maturation over the first month of life, regardless of body site. Key body-site-specific taxa, but not overall fungal community structures, were impacted by birth mode. Thus, additional studies to characterize mycobiome acquisition and succession throughout early life are needed to form a foundation for research into the relationship between mycobiome development and human disease.

Keywords: ITS2; fungi; infant; microbiome; mycobiome.

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Figures

FIG 1
FIG 1
Infant mycobiomes vary by body site. (a) Principal-coordinate analysis of weighted UniFrac distances for infant skin, oral, and anal mycobiomes over the first 30 days of life. Box plots shown along each axis represent the median and interquartile range and indicate the distribution of samples along the given axis. Each point represents a single sample and is colored by body site as follows: skin, yellow (n = 58 samples); oral, teal (n = 56 samples); anal, pink (n = 60 samples). PERMANOVA values, R2 values, and P values are shown. (b and c) The same principal-coordinate analysis colored by the relative abundances of (b) Candida albicans and (c) C. parapsilosis, with anal samples denoted with a solid border. (d and e) Relative abundances of (d) C. albicans and (e) C. parapsilosis within the skin, oral, and anal mycobiomes of infants, as assessed by Wilcoxon rank sum tests with false-discovery-rate correction.
FIG 2
FIG 2
Specific taxa within the infant skin, oral, and anal mycobiomes. (a) Numbers of observed taxa within the skin, oral, and anal mycobiomes of infants, as assessed by Student’s t tests. (b) Relative abundances of fungal taxa within each body site. Each bar represents an individual sample, and samples are ordered by infant. The union of the 10 most abundant and 10 most common taxa is shown. “Other” represents taxa whose relative abundance is <10%. A full taxon legend is located in Fig. S1c.
FIG 3
FIG 3
Infant mycobiome dynamics during the first 30 days of life. Data represent results of principal-coordinate analysis (a, c, and e) of weighted UniFrac (W-Unifrac) distances and median within-infant and between-infant weighted UniFrac distances (b, d, and f) for (a and b) skin, (c and d) oral, and (e and f) anal mycobiomes over time. Principal-coordinate analysis data (individual infant data noted by distinct colored shape; see legend) were tested with PERMANOVA; R2 values and P values are shown. Distances were compared using a Wilcoxon rank sum test (n = 17 infants).
FIG 4
FIG 4
Infant alpha diversity over time. Shannon index values corresponding to fungal OTUs from (a) skin, (b) oral, and (c) anal mycobiomes are presented (n = 17 infants). P values represent group-wise averages of permuted Spearman correlation test statistics controlled by subject. The dotted lines represent a summary linear model that controls for subject, with R2 reported.
FIG 5
FIG 5
Infant skin and oral mycobiomes by birth mode. (a) Principal-coordinate analysis of weighted UniFrac distances of infant skin mycobiomes colored by birth mode (vaginal = blue, n = 30 samples; caesarean section = green, n = 28 samples). PERMANOVA values, R2 values, and P values are shown. (b and d) Weighted UniFrac distances of infant (b) skin and (d) oral mycobiomes from the mother’s vaginal mycobiome by birth mode (paired analysis), as assessed by a Wilcoxon rank sum test (n = 7 vaginal birth families and 9 caesarean section birth families across all time points). (c and e) Relative abundances of (c) Candida albicans in infant skin on day 30 according to birth mode and (e) C. orthopsilosis in the oral cavity across all time points, as assessed with a Wilcoxon rank sum test (false discovery rate corrected; n = 5 vaginally born infants, n = 6 caesarean section-born infants).

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