Reproductive experience influences the effects of Lactocaseibacillus rhamnosus HN001 on gut microbiota and hippocampal plasticity in female rats.

There is increasing interest in the role of probiotics in supporting maternal well-being throughout female reproduction. However, it remains largely unknown whether the brain of a female with reproductive experience responds differently to probiotics compared to females without reproductive experience. Reproduction involves remarkable neuroplasticity; therefore, we hypothesized that reproducing females are particularly susceptible to the effects of probiotic treatment. Groups of early pregnant or age-matched virgin female Long-Evans rats were administered the probiotic, Lactocaseibacillus rhamnosus HN001 (HN001), in their drinking water or given untreated water for 30 days. To measure changes in gut microbiota, fecal samples were taken regularly. Brains were analyzed at the end of treatment to quantify hippocampal cells containing the neurogenesis marker doublecortin, the synaptic marker synaptophysin, and the microglial activation marker Iba1. For dams, an offspring retrieval test was performed. Main findings show that HN001 administration lowers Bacteroidota abundance in the gut regardless of reproductive experience. In HN001-treated dams there was an increase in the number of times offspring were carried and this was negatively correlated with Bacteroidota abundance in the dam's gut. HN001-treated dams also had more immature neurons in the hippocampus and more thick-type microglial cells in the dorsal hippocampus compared to control dams. HN001-treated females, regardless of reproductive experience, had lower density of synaptophysin immunoreactivity in the CA1, and more thick-type microglia cells in the ventral hippocampus, compared to control females. These results indicate that the probiotic, HN001, alters female rat maternal behavior, plasticity in the hippocampus, and the gut microbiota abundance, with some effects being influenced by reproductive experience.