Abstract
Following birth, the neonatal intestine is exposed to maternal and environmental bacteria that successively form a dense and highly dynamic intestinal microbiota. Whereas the effect of exogenous factors has been extensively investigated, endogenous, host-mediated mechanisms have remained largely unexplored. Concomitantly with microbial colonization, the liver undergoes functional transition from a hematopoietic organ to a central organ of metabolic regulation and immune surveillance. The aim of the present study was to analyze the influence of the developing hepatic function and liver metabolism on the early intestinal microbiota. Here, we report on the characterization of the colonization dynamics and liver metabolism in the murine gastrointestinal tract (n = 6–10 per age group) using metabolomic and microbial profiling in combination with multivariate analysis. We observed major age-dependent microbial and metabolic changes and identified bile acids as potent drivers of the early intestinal microbiota maturation. Consistently, oral administration of tauro-cholic acid or β-tauro-murocholic acid to newborn mice (n = 7–14 per group) accelerated postnatal microbiota maturation.
Highlights
Following birth, the neonatal intestine is exposed to maternal and environmental bacteria that successively form a dense and highly dynamic intestinal microbiota
All sequences were subsequently clustered based on de novo assembly into 478 operational taxonomic units (OTUs) that were taxonomically classified to the genus level
Ursodeoxycholic acid (UDCA), glycine-conjugated cholic acid (GCA), Taurineconjugated α/β-muricholic acid (TMCA), and taurineconjugated cholic acid (TCA) are significantly associated with the compositional changes of the microbiota with age and represent good candidates of host-derived factors that drive postnatal establishment of the enteric microbiota
Summary
The neonatal intestine is exposed to maternal and environmental bacteria that successively form a dense and highly dynamic intestinal microbiota. The early postnatal colonization process is of critical importance for the long-term microbiota composition[6], and immune maturation and thereby the susceptibility to highly prevalent non-communicable diseases[7]. Microbiota alterations during this time window have been associated with adverse consequences and an enhanced susceptibility to disease[8,9]. The process of intestinal bacterial colonization after birth has been intensively studied during the last years and exogenous factors which significantly impact the early microbiota composition have been identified[3,5,12,13,14,15]. Multi-omics analysis identifies specific bile acids associated with maturation of the early intestinal microbiota and subsequent interventional studies functionally confirm and specify the role of specific bile acids as important drivers of microbiota development
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