Gut microbiota and BMI throughout childhood: the role of firmicutes, bacteroidetes, and short-chain fatty acid producers

Abstract

Childhood obesity is a risk factor for numerous health conditions. A critical factor in the etiology of obesity appears to be the gut microbiota, which is the microbial community that resides in the human gut. The ratio of the phyla Firmicutes and Bacteroidetes (F/B) and gut bacterial genera that produce short-chain fatty acids (SCFA) have been suggested to contribute to obesity. The current study investigated (1) whether differences in F/B ratio can be observed in infancy and childhood in relation to zBMI in healthy children, and (2) whether an innovative proxy measure adds evidence to a relationship between SCFA producers and the etiology of obesity. Stool samples were collected at five time points, and zBMI was assessed at eight time points throughout the first 12 years of life. Our confirmatory analyses with Bayesian multilevel models showed no relationship between the F/B ratio and zBMI. Also, a proxy measure constructed from known SCFA producers was unrelated to zBMI throughout the first 12 years of life. Exploratory analyses using multilevel and random forest models suggest that the relative abundances of Firmicutes and Bacteroidetes were independently negatively associated with zBMI from infancy through childhood, and the SCFA producing genera Subdoligranulum and Alistipes were negatively related to future BMI in childhood.

Figure 1

Individual and median trajectories of microbiota variables and BMI. (A) Individual and median (in red) trajectories of F/B ratio on log10 scale over time. (B) Individual and median trajectories of relative abundance of sum SCFA producers over time. (C) Individual and median (raw) BMI trajectories over time split by sex. Error bars indicate interquartile range (IQR). Please note the break in the x-axis. The lines crossing the break do not represent the actual slope and are only plotted to show individual growth trajectories.

Figure 2

Gut microbiota composition over time. (A) The average relative abundance of the 6 most abundant phyla in the first 12 years of life are shown with Actinobacteria predominating in infancy and Firmicutes becoming the predominant phylum in childhood. Phyla with an abundance < 1% are plotted as “Other”. (B) The composition of average relative abundance of SCFA producer genera in the first 12 years of life is shown. In infancy, Bifidobacterium is the dominant genus of SCFA producers with the composition becoming more diverse in childhood. Note that y-axes are not equivalent.

Figure 3

Spearman correlation matrices of main predictor and outcome varables. (A) Correlation Matrix between zBMI and F/B ratio over the ages. (B) Correlation matrix between zBMI and SCFA producers over the ages. Colored squares indicate significant values (p < 0.05).

Figure 4

Posterior distribution (median and 95% credible interval) of $\mathrm{\beta }$ coefficients (slopes) per SCFA producer. (A) All samples. (B) Only infant samples. (C) Only childhood samples.