Correlation of gut microbiota and neurotransmitters in a rat model of post-traumatic stress disorder

Abstract

Objective: To determine the effect of gut microbiota on a rat model of post-traumatic stress disorder (PTSD) and explore the correlation of gut microbiota with behavior and neurotransmitters. Methods: We established a single prolonged stress (SPS) model to examine the pathogenesis of PTSD on rat behavior, gut microbiota, and neurotransmitter levels. Rats were separated into control and model groups, and neurotransmitter levels were measured using enzyme linked immunosorbent assay. Then, 16 S rRNA sequencing was used to compare the gut microbiota between the control and model groups. Results: Compared with those in the control group, freezing time significantly increased, while number of standing upright, crossing frequency, time spent in the central arena, and total distance traveled were significantly reduced in the model group after exposure to SPS (all P < .05). Meanwhile, serotonin, or 5-hydroxytryptamine, levels in the brain in the model group were significantly lower than those the control group (P = .0332). In addition, changes were observed in the gut microbiota diversity and relative abundances of bacterial phyla, orders, families, and genera in the model group. Especially, changes in Firmicutes, Bacteroidetes, Cyanobacteria, and Proteobacteria levels were most pronounced after SPS exposure. Correlation analysis showed that the strongest positive correlation was found between Bacteroidaceae and 5-HT (P = .0009). Moreover, RF32 abundance was the most negatively related to 5-HT (P = .0009), crossing frequency (P = .0007), and total distance (P = .0003). Conclusion: Our results suggest that SPS model rats showed differences in behavior, neurotransmitter levels, and gut microbiota with control rats. Moreover, Firmicutes, Bacteroidetes, Cyanobacteria, and Proteobacteria were most relevant to the exhibited fear-like and anxiety-like behaviors and significant serotonin content reduction in SPS model rats.

Keywords

• Post-traumatic stress disorder
• Single prolonged stress
• Gut microbiota
• 5-Hydroxytryptamine
• Behavior