Objective  To explore influences and mechanisms of various maternal stress exposures on gut microbiota structure in offspring rats.

  Methods   Chronic unpredictable mild stress (CUMS) was conducted 3 days before mating continuously for 3 weeks to establish stress model and Lycium barbarum polysaccharide (LBP) was used as an anti-stress agent administered by gavage at the dosage of 40 mg/kg once a day continuously for 2 weeks beginning 8 days after the CUMS treatment in 32 female healthy adult Sprague-Dawley (SD) rats. The experimental rats were randomly divided into 4 groups (8 in each group): a control group without CUMS, a LBP treated control group without CUMS, a model group with CUMS, and a model group with CUMS and LBP. The offspring rats were weaned at postnatal day (PND) 21; the offspring rats′ fresh feces specimens of were sampled 20 days after the birth and their angula vein blood samples were collected 28 days and 42 days after the birth. Plasma corticosterone was determined with radioimmunoassay; the metabolites of gut microbiota in plasma of offspring rats were detected with enzyme-linked immunosorbent assay (ELISA). Illumina MiSeq sequencing technology was used to determine sequences of the 16S rRNAV3-V4 region of microorganisms in rat feces. Correlations between plasma indicators and gut microbiota structure of the offspring rats were analyzed statistically.

  Results  The plasma corticosterone increased significantly in the model rats and the LBP-treated model rats compared to that in the control rats and the LBP-treated control rats (P < 0.05). The plasma corticosterone, short-chain fatty acids (SCFA), cholecystokin (CCK), 5-hydroxytryptamine (5-HT), and γ-aminobutyric acid (GABA) and the gut microbiota diversity index were all significantly different among the offspring rats with various maternal stress exposure (P < 0.05 for all). For the offspring rats, the relative abundance of Lactobacillaceae, Muribaculaceae, and Prevotellaceae in the gut microbiota were relatively high; stronger impact of SCFA and CCK on the gut microbiota diversity index were observed; the plasma contents of GABA and 5-HT were inversely correlated significantly with the relative abundance of Victivallaceae (P < 0.05); the PND 42 body weight was inversely correlated with the relative abundance of Pasteurellaceae (P < 0.05); and the PND 28 plasma corticosterone was inversely correlated with the relative abundance of Bacteroidaceae (P < 0.05).

  Conclusion  Maternal stress exposure can influence gut microbiota structure in offspring rats and the influence is associated with the variation in maternal and offspring rats′ plasma corticosterone.