Diurnal rhythmicity of fecal microbiota and metabolite profiles in the first year of life: a randomized controlled interventional trial with infant formula

Abstract

Microbiota assembly in the infant gut is influenced by time and duration of dietary exposure to breast-milk, infant formula and solid foods. In this randomized controlled intervention study, longitudinal sampling of infant stools (n=998) showed similar development of fecal bacterial communities between formula- and breast-fed infants during the first year of life (N=210). Infant formula supplemented with galacto-oligosaccharides (GOS) was most efficient to sustain high levels of bifidobacteria compared to formula containingB. longumandB. breveor placebo. Metabolite (untargeted) and bacterial profiling (16S rRNA/shallow metagenomics sequencing) revealed 24-hour oscillations and integrated data analysis identified circadian networks. Rhythmicity in bacterial diversity, specific taxa and functional pathways increased with age and was most pronounced following breast-feeding and GOS-supplementation. Circadian rhythms in dominant taxa were discoveredex-vivoin a chemostat model. Hence microbiota rhythmicity develops early in life, likely due to bacterial intrinsic clock mechanism and is affected by diet.