Exploring the use of exhaled breath profiling for non-invasive monitoring of cognitive functioning in children: a pilot study.

INTRODUCTION: Childhood is a critical period for the development of executive functioning skills, including selective attention and inhibitory control, which are essential for cognitive development. Optimal brain development during this time requires appropriate levels of macronutrient intake. Metabolomics can offer valuable insights into which metabolites cognitive functioning and the underlying gut-brain interactions. OBJECTIVES: This study aimed to explore to use of breathomics to investigate associations between exhaled metabolites and executive functioning in children. METHODS: Children (8-10 years; N = 31) were recruited via flyers at schools and after-school care. The assessment of executive functioning was done using Eriksen flanker task. Breath samples were collected in Tedlar(®) bags and analyzed with proton transfer reaction-mass spectrometry (PTR-MS). On-breath peaks were selected and subjected to partial least squares (PLS) regression. Significance multivariate correlation (sMC) was used afterwards to select metabolites bearing predictive power towards executive functioning. RESULTS: Gut microbiome-related metabolites (methane, ethanol, and butyric acid) present in exhaled breath were associated with an improved executive functioning, whereas isoprene was linked to reduced executive functioning. Additionally, increased levels of inflammatory markers, ethylene and acetaldehyde, were associated with a higher compatibility effect in error rates, suggesting diminished cognitive control. These VOCs were putatively linked with specific gut microbial taxa; for instance, reduced Bacteroidetes abundance (associated with methane production) is associated with decreased inhibitory control, while Enterobacteriaceae were linked to lipopolysaccharide-induced inflammation which is also a process that causes increased ethylene production. CONCLUSION: This proof-of-concept study demonstrates that VOCs in exhaled breath could serve as a promising non-invasive tool for assessing gut-brain interactions related to executive functioning in children.