Metabolomic signature of the maternal microbiota in the fetus

Abstract

The maternal microbiota affects the development of the offspring potentially by microbial metabolites translocating to the foetus through the placenta. We compared placentae, foetal intestine and brain from germ-free (GF) and specific pathogen free (SPF) mouse dams by non-targeted metabolomic profiling. 100 annotated metabolites and altogether 3680 molecular features had significantly different levels in the placental and/or foetal tissues of GF and SPF mice. More than half of the annotated and differentially expressed metabolites had decreased levels in the GF tissues, suggesting their microbial origin or a metabolic response of the host to the presence of gut microbiota. These include known or suggested microbial metabolites, such as 5-aminovaleric acid betaine, (β-)alanine betaine, trimethylamine N-oxide, catechol-O-sulfate, and hippuric acid. Several metabolites had increased levels in the GF mice. These could be precursors of microbial metabolites or indicators of a metabolic response to the absence of gut microbiota. 99 molecular features were only detected in the SPF mice, suggesting the existence of unidentified microbially modified metabolites that potentially influence fetal development. Only a few molecular features showed significantly different levels in the placental tissues but not in other tissues, indicating that the potential microbial metabolites mostly pass through the placenta into the foetus.