Potential of Limosilactobacillus reuteri in modulating neuroplasticity and ameliorating behavioral deficits in a maternal separation rat model of autism.

Abstract

Limosilactobacillus reuteri has attracted attention for its potential to modulate the gut-brain axis. This study investigates whether L. reuteri administration mitigates autism-related abnormalities in a maternal separation rat model of autism. Male Wistar rats were divided into maternal-separated L. reuteri-treated (MS+LR), maternal-separated placebo-treated (MS), and non-separated control groups. Behavioral assessments evaluated autism-related behaviors, including social interaction, repetitive behavior, anxiety, and hyperactivity. Immunohistochemical analysis of the hypothalamus assessed oxytocin expression, while 3D stereological analysis of the medial prefrontal cortex (mPFC) examined brain structure in the infralimbic (IL) and anterior cingulate cortex (ACC). Absolute quantification of fecal L. reuteri was performed using quantitative real-time PCR. The MS+LR group showed significantly higher L. reuteri colonization, improved social behaviors, and reduced repetitive behaviors. Immunohistochemical findings revealed normalized oxytocin expression in the paraventricular nucleus (PVN) of the MS+LR group, suggesting a neurobiological mechanism. The IL volume and neuron number in the MS group were significantly increased compared to the control and MS+LR groups, while the ACC volume and neuron number were significantly decreased. These findings suggest that L. reuteri ameliorates autism-like symptoms induced by maternal separation by modulating brain structure through oxytocin-dependent pathways.