Multifactorial effects of probiotic Parasutterella excrementihominis on gestational inflammation, offspring behaviour and prenatal-stress induced disruptions in tryptophan metabolism.

Abstract

Prenatal stress (PNS) has widespread effects on offspring, including aberrant immune development and behavioural deficits. The microbiome is a mediator of the dissemination of stress effects to the offspring through immunomodulation and metabolite production. Metabolites derived from the mother and their gut microbiota pass to the foetus and can affect immune and nervous development. Stress affects the abundance of such metabolites, including the tryptophan (Trp) pathway, which are involved in immune and nervous system function. We hypothesized that the PNS is associated with dysregulation of Trp metabolism. We further posited that treatment with a Trp-metaboliser Parasutterella excrementihominis would abrogate PNS-associated deleterious effects on offspring development. To test this hypothesis, pregnant mice were exposed to restraint stress and administered P. excrementihominis (Dam n = 3-9; Offspring n = 5-10). PNS increased maternal gut Trp and both maternal and offspring inflammation. P. excrementihominis treatment reduced the PNS-induced excess pool of maternal gut Trp. Some PNS effects on foetal neuroinflammation were reduced in severity due to handling effects from bacterial gavage. However, P. excrementihominis was anti-inflammatory in dam and offspring and anxiolytic in offspring of Pe-treated dams. These data illustrate that elevated Trp levels are associated PNS and its downstream deleterious offspring inflammatory and behavioural outcomes while P. excrementihominis, a Trp-metabolizer, can ameliorate these effects and improve offspring outcomes.