Early Gut Fungal and Bacterial Microbiota and Childhood Growth

Abstract

Introduction: Childhood growth is a sensitive marker of health. Animal studies show increased height and weight velocity in the presence of fungal as well as antibiotic supplement in feed. Human studies on early gut microbiota and anthropometrics have mainly focused on bacteria only and overweight, with diverging results. We thus aimed to investigate the associations between childhood growth [height and body mass index (BMI)] and early fungal and bacterial gut microbiota. Methods: In a population-based cohort, a subset of 278 pregnant mothers was randomized to drink milk with or without probiotic bacteria during and after pregnancy. We obtained fecal samples in offspring at four time points between 0 and 2 years and anthropometric measurements 0 and 9 years. By quantitative PCR and 16S/ITS rRNA gene sequencing, children's gut microbiota abundance and diversity were analyzed against height standard deviation score (SDS) and BMI-SDS and presented as effect estimate (β) of linear mixed models. Results: From 278 included children (149 girls), 1,015 fecal samples were collected. Maternal probiotic administration did not affect childhood growth, and the groups were pooled. Fungal abundance at 2 years was positively associated with height-SDS at 2-9 years (β = 0.11 height-SDS; 95% CI, 0.00, 0.22) but not with BMI-SDS. Also, higher fungal abundance at 1 year was associated with a lower BMI-SDS at 0-1 year (β = -0.09 BMI-SDS; 95% CI, -0.18, -0.00), and both bacterial abundance and bacterial alpha diversity at 1 year were associated with lower BMI-SDS at 0-1 year (β = -0.13 BMI-SDS; 95% CI, -0.22, -0.04; and β = -0.19 BMI-SDS; 95% CI, -0.39, -0.00, respectively). Conclusions: In this prospective cohort following 0-9-year-old children, we observed that higher gut fungal abundances at 2 years were associated with taller children between 2 and 9 years. Also, higher gut fungal and bacterial abundances and higher gut bacterial diversity at 1 year were associated with lower BMI in the first year of life. The results may indicate interactions between early gut fungal microbiota and the human growth-regulating physiology, previously not reported. Clinical Trial Registration: Clinicaltrials.gov, NCT00159523.

Keywords: childhood growth; fungi; gut microbiota; height velocity; mycobiota.

Copyright © 2020 Schei, Simpson, Avershina, Rudi, Øien, Júlíusson, Underhill, Salamati and Ødegård.

Figures

Figure 1

Abundances and alpha diversities for fungi and bacteria. Abundance and alpha diversity data for fungi and bacteria for children's samples at different ages [10 days, 3 months, 1, and 2 years; fungal data reported in (15)]. The average fungal abundances (A) decreased significantly (P = 0.01) from 10 days (2.83 log ITS/ml) to 1 year (2.19 log ITS/ml). The dashed blue line indicates the sequencing cut-off for fungi. Similarly, the bacterial abundance (B) decreased significantly (P = 0.04) from 10 days (6.31 log 16S/ml) to 3 months (6.06 log 16S/ml), and then increased toward 1 year (7.00 log 16S/ml, P < 0.01). There was insufficient data to determine the effect of age on the fungal alpha diversity (C); however, bacterial alpha diversity (D) increased steadily from its lowest at 10 days (1.30 H′) and highest at 2 years (2.86 H′, P < 0.01). Cesarean section was associated with a non-significant trend toward lower bacterial alpha diversity at 3 months of age (1.09 vs. 1.36 H′, P = 0.06). Diamonds indicate sample means and error bars cover the 95% CI.

Figure 2

Bar charts of fungal and bacterial gut communities. (A) Mean relative abundances for the fungal genera (>1% abundant) for each age group. Each color designates a genus. Number of samples for each bar is stated in brackets below the bar. (B) Mean relative abundances for the bacterial genera for each age group. Each color designates a genera. The number of samples is stated in brackets below the bar.

Figure 3

BMI-SDS and height-SDS and microbial abundance as predicted linear associations. (A) Predictions of BMI-SDS at 0–1 year for fungal and bacterial abundances. (B) Prediction of height-SDS at 2–9 years for fungal and bacterial abundance. The predictions are shown as lines, and the colored areas cover the 95% CI. The bacterial abundance prediction model for height-SDS remains statistically non-significant.

Figure 4

Mean height-SDS and BMI-SDS at 0–1 years according to microbiota abundances at 1 year. Mean standard deviation scores (SDS) values for children at 0–1 year with four quartiles of microbiota abundances at 1 year. Group mean height-SDS at 0–1 year for four quartiles of abundances of fungi (A) and bacteria (B). Group mean BMI-SDS at 0–1 year for high or low abundances of fungi (C) and bacteria (D).

Figure 5

Mean height-SDS and BMI-SDS at 2–9 years according to microbiota abundances at 2 years. Mean standard curve deviation (SDS) values for children at 2–9 years with four quartiles of microbiota abundances at 2 years. Group mean height-SDS at 2–9 years for four quartiles of abundances of fungi (A) and bacteria (B). Group mean BMI-SDS at 2–9 years for high or low abundances of fungi (C) and bacteria (D).