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. 2022 Jan;17(1):e12833.
doi: 10.1111/ijpo.12833. Epub 2021 Jul 30.

Metabolomic profiling of stool of two-year old children from the INSIGHT study reveals links between butyrate and child weight outcomes

Debmalya Nandy  1 , Sarah J C Craig  2   3 , Jingwei Cai  4 , Yuan Tian  4 , Ian M Paul  3   5 , Jennifer S Savage  6   7 , Michele E Marini  7 , Emily E Hohman  7 , Matthew L Reimherr  1   3 , Andrew D Patterson  4   8 , Kateryna D Makova  2   3 , Francesca Chiaromonte  1   3   9
Affiliations

Metabolomic profiling of stool of two-year old children from the INSIGHT study reveals links between butyrate and child weight outcomes

Debmalya Nandy et al. Pediatr Obes. 2022 Jan.

Abstract

Background: Metabolomic analysis is commonly used to understand the biological underpinning of diseases such as obesity. However, our knowledge of gut metabolites related to weight outcomes in young children is currently limited.

Objectives: To (1) explore the relationships between metabolites and child weight outcomes, (2) determine the potential effect of covariates (e.g., child's diet, maternal health/habits during pregnancy, etc.) in the relationship between metabolites and child weight outcomes, and (3) explore the relationship between selected gut metabolites and gut microbiota abundance.

Methods: Using 1 H-NMR, we quantified 30 metabolites from stool samples of 170 two-year-old children. To identify metabolites and covariates associated with children's weight outcomes (BMI [weight/height2 ], BMI z-score [BMI adjusted for age and sex], and growth index [weight/height]), we analysed the 1 H-NMR data, along with 20 covariates recorded on children and mothers, using LASSO and best subset selection regression techniques. Previously characterized microbiota community information from the same stool samples was used to determine associations between selected gut metabolites and gut microbiota.

Results: At age 2 years, stool butyrate concentration had a significant positive association with child BMI (p-value = 3.58 × 10-4 ), BMI z-score (p-value = 3.47 × 10-4 ), and growth index (p-value = 7.73 × 10-4 ). Covariates such as maternal smoking during pregnancy are important to consider. Butyrate concentration was positively associated with the abundance of the bacterial genus Faecalibacterium (p-value = 9.61 × 10-3 ).

Conclusions: Stool butyrate concentration is positively associated with increased child weight outcomes and should be investigated further as a factor affecting childhood obesity.

Keywords: 1-HNMR; butyrate; childhood obesity; metabolomics; weight outcomes at 2-years.

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Conflict of interest statement

The authors declare no financial or other conflicts of interests.

Figures

FIGURE 1
FIGURE 1
Schematic of objectives of the current study. The bold solid arrow represents our main objective: to investigate the relationship between gut metabolites and child weight outcomes (1). Lighter arrows represent related objectives: to investigate effects of covariates recorded on children and mothers as direct effects (solid) and through interactions with butyrate (dashed) on child weight outcomes (2). We also investigate the relationship between the gut microbiota and the gut metabolites (3)
FIGURE 2
FIGURE 2
Relationship between butyrate adjusted metabolite concentration and BMI of 170 INSIGHT children. (A) A scatterplot of BMI against butyrate concentration with a simple regression trend line (R2 = 0.0729, p‐value = 3.58 × 10−4). The colours (horizontal bands) correspond to approximate BMI class cut‐offs (yellow = underweight, blue = normal weight, green = overweight, purple = obese) and match those in panel (B). (B) Boxplots of butyrate concentration by BMI class. The width of the boxes are proportional to the number of individuals within each class (underweight: 9, normal weight: 137, overweight: 16, obese: 8). a = children with overweight have greater average butyrate adjusted metabolite concentration than children with normal weight, p‐value = 0.0312 (one‐sided t‐test). b = children with obesity have greater average adjusted metabolite concentration than children with normal weight, p‐value = 0.0176 (one‐sided t test)
FIGURE 3
FIGURE 3
Relationship between the abundance of different groups of bacteria and butyrate adjusted metabolite concentration. (A) All bacteria classified as Firmicutes; (B) All bacteria identified in Vital et al. as having butyrate synthesis potential; (C) Firmicute bacteria with butyrate synthesis potential, as identified in Vital et al.; (D) Faecalibacterium (one outlier was removed). The black solid lines indicate the fitted linear regression models; the R2 and the p‐values correspond to Pearson's correlation
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