AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health long-lastingly. Here, we determined how beneficial microbiome interventions in early life affect metabolic health in adulthood.

METHODS: Postnatal diets were supplemented with either prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M-16V) until post-natal (PN) day 42 in a well-established rodent model for nutritional programming. Mice were subsequently challenged with high-fat Western-style diet (WSD) for eight weeks. Body weight and composition were monitored, as was gut microbiota composition at PN21, 42 and 98. Markers of glucose homeostasis, lipid metabolism and host transcriptomics of six target tissues were determined in adulthood (PN98).

RESULTS: Early life synbiotics protected mice against WSD-induced excessive fat accumulation throughout life, replicable in two independent European animal facilities. Adult insulin sensitivity and dyslipidemia were improved and most pronounced gene expression changes were observed in the ileum. We observed subtle changes in fecal microbiota composition, both in early life and in adulthood, including increased Bifidobacterium abundance. Microbiota transplantation using samples collected from synbiotics-supplemented adolescent mice at PN42 to age-matched germ-free recipients did not transfer the beneficial phenotype, indicating that synbiotics-modified microbiota at PN42 is not sufficient to transfer the long-lasting protection of the metabolic health status.

CONCLUSION: Together, these findings show the potential and importance of timing of synbiotic interventions in early life during crucial microbiota development as preventive measure to ameliorate obesity risk and improve metabolic health throughout life.