Fecal tryptophan metabolism predicts the development of infant eczema: a prospective longitudinal study

Early-life microbial metabolism of tryptophan plays a critical role in immune modulation and may influence susceptibility to inflammatory disorders such as eczema. However, longitudinal human data linking microbial tryptophan metabolism to eczema onset are limited. We conducted a prospective cohort study of 40 term-born UK infants, followed from birth to 24 months, stratified by early-onset (infants developing eczema <12 months, n = 12) or late-onset (infants developing eczema ≥12 months, n = 7) doctor-diagnosed eczema. Fecal samples underwent targeted tryptophan LC-MS metabolomics and 16S rRNA sequencing. Tryptophan metabolomics revealed dynamic changes in tryptophan metabolites that were associated with disease status compared to healthy infants. Infants with early-onset eczema (<12 months) exhibited elevated tryptophan and tryptamine levels at 6 months, while those with late-onset eczema (≥12 months) showed reduced indole-3-lactic acid (ILA) levels prior to diagnosis at 9 months. 16S and metabolomics correlations highlighted a metabolic shift in Bifidobacterium from ILA, a metabolite that predominated fecal metabolome during early infancy but decreases by 12 months, coinciding with increased indole-3-aldehyde (I3AD) metabolism by Bifidobacterium. Receiver operating characteristic (ROC) curve analysis identified a small panel of early predictive indole-pathway markers, including tryptophan and the indole/indole-3-sulfate (I3S), I3S/ILA, and tryptophan/ILA ratios, discriminating both early- and late-onset eczema development. Our findings reveal distinct, time-dependent disruptions in microbial tryptophan cometabolism associated with eczema onset. ILA may serve as a biomarker for the diagnosis of infantile eczema. Further validation studies to establish its clinical utility are now required.