Child Weight Gain Trajectories Linked To Oral Microbiota Composition

Sarah J C Craig, Daniel Blankenberg, Alice Carla Luisa Parodi, Ian M Paul, Leann L Birch, Jennifer S Savage, Michele E Marini, Jennifer L Stokes, Anton Nekrutenko, Matthew Reimherr, Francesca Chiaromonte, Kateryna D Makova, Sarah J C Craig, Daniel Blankenberg, Alice Carla Luisa Parodi, Ian M Paul, Leann L Birch, Jennifer S Savage, Michele E Marini, Jennifer L Stokes, Anton Nekrutenko, Matthew Reimherr, Francesca Chiaromonte, Kateryna D Makova

Abstract

Gut and oral microbiota perturbations have been observed in obese adults and adolescents; less is known about their influence on weight gain in young children. Here we analyzed the gut and oral microbiota of 226 two-year-olds with 16S rRNA gene sequencing. Weight and length were measured at seven time points and used to identify children with rapid infant weight gain (a strong risk factor for childhood obesity), and to derive growth curves with innovative Functional Data Analysis (FDA) techniques. We showed that growth curves were associated negatively with diversity, and positively with the Firmicutes-to-Bacteroidetes ratio, of the oral microbiota. We also demonstrated an association between the gut microbiota and child growth, even after controlling for the effect of diet on the microbiota. Lastly, we identified several bacterial genera that were associated with child growth patterns. These results suggest that by the age of two, the oral microbiota of children with rapid infant weight gain may have already begun to establish patterns often seen in obese adults. They also suggest that the gut microbiota at age two, while strongly influenced by diet, does not harbor obesity signatures many researchers identified in later life stages.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Growth curves construction. (a) Example growth curve. Points: observed weight-for-length ratios (i.e. growth indexes); line: estimated growth curve. (b) Final aligned growth curves for all children studied.
Figure 2
Figure 2
Oral and Gut microbiota’s relationships with growth curves. Estimated regression coefficient curves expressing the associations of growth curves with (a) children’s gut α-diversity, (b) children’s oral α-diversity, (c) mothers’ oral α-diversity, (d) children’s gut Firmicutes-to-Bacteroidetes ratio, (e) children’s oral Firmicutes-to-Bacteroidetes ratio and (f) mothers’ oral Firmicutes-to-Bacteroidetes ratio. Each curve is accompanied by a point-wise confidence band.
Figure 3
Figure 3
Oral and Gut microbiota’s relationships with conditional weight gain. Notched box-plots contrasting α-diversity and Firmicutes-to-Bacteroidetes (F:B) ratio in two-year-old children with rapid (CWG ≥ 0) vs. non-rapid (CWG a,d) for the gut microbiota in children with rapid (N = 90) vs. non-rapid (N = 99) weight gain; (b,e) for the oral microbiota in children with rapid (N = 97) vs. non-rapid infant weight gain (N = 117); (c,f) for the oral microbiota in mothers of children with rapid infant weight gain (N = 102) vs. mothers of children without rapid infant weight gain (N = 113). All p-values were obtained using one-tailed Mann-Whitney U tests, significant p-values are shown in bold. Outliers were not plotted but were included in the statistical tests.
Figure 4
Figure 4
Identification of influential taxonomic groups. Estimated regression coefficient curves for taxonomic groups affecting growth curves, as identified by FLAME in (a) children’s gut microbiota, (b) children’s oral microbiota, (c) mothers’ oral microbiota. The zero line (dashed) corresponds to no effect. Linear Discriminant Analysis scores for taxonomic groups distinguishing children with rapid vs. non-rapid infant weight gain, as identified by LEfSe in (d) children’s gut microbiota, (e) children’s oral microbiota. See Supplementary Table S8 for a list of genera belonging to each group identified by FLAME and LEfSe.

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