To investigate the preventive effect of inulin-type oligosaccharides of Morinda officinalis (IOMO) against post-traumatic stress disorder (PTSD) like behaviors induced by inescapable electric foot-shock (Fs) in mice and the underlying mechanism.

A mouse model of PTSD was established using inescapable electric Fs. Mice were randomly divided into the control group, Fs group, Fs+sertraline (Ser) positive drug group, and Fs+IOMO prevention group. The IOMO group was administered with 50 mg/kg IOMO once daily by intragastric gavage (ig) for 10 consecutive days before modeling. PTSD like behaviors were evaluated using the contextual fear paradigm (CFP), open field test (OFT), and elevated plus maze (EPM). Gut microbiota composition was analyzed by 16S rRNA sequencing. Pathological changes in colon tissue were observed by HE staining. Levels of lipopolysaccharide (LPS), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the serum and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). Protein expressions of Claudin 1 in colon tissue and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in the hippocampus were detected by Western blotting.

Compared with the control group, mice in the Fs group exhibited significant PTSD like behaviors without affecting spontaneous activity, as evidenced by prolonged freezing time in the CFP, prolonged latency to enter the intermediate zone and reduced percentage of distance traveled in the intermediate zone in the OFT, and prolonged latency to enter the open arm and reduced percentage of distance traveled in the open arm in the EPM. Preventive administration of IOMO for 10 days before modeling significantly reversed these PTSD like behaviors. Meanwhile, significant disturbance of gut microbiota composition was observed in the Fs group, which was markedly restored by IOMO pretreatment. In the Fs group, colon Claudin-1 expression was decreased, while serum and hippocampal LPS levels as well as hippocampal NLRP3 and inflammatory cytokine levels were significantly increased. IOMO significantly reversed these changes.

Preventive administration of IOMO can effectively prevent PTSD like behaviors in mice. This effect may be associated with regulation of gut microbiota, enhancement of intestinal barrier function, and alleviation of hippocampal neuroinflammation. This study provides correlative evidence for the gut-brain axis mediating the preventive effect of IOMO against PTSD.