| 其他摘要 | Depression is a complex mental disorder with persistent depression, decreased in-terest, and anhedonia as the main core symptoms. Demonstrating the relationship be-tween intestinal microbiota and depression provides a theoretical basis for the use of probiotics to assist in the treatment of depression. Probiotics can play a positive role in the therapy of depression through the brain-gut axis, but the molecular mechanism re-mains unclear. Due to the limitations of clinical research, this study selects a chronic social defeat stress mice depression model as the study subject with treatment of probi-otic, analyzing the mechanism of probiotics' influence on the behavioral phenotype and physiological function of depressed mice from three aspects: behavioral measurement, intestinal microbiota and inflammatory system.
Probiotic resource is the basis of this research. Through separation, purification and identification from probiotic powder, a total of 5 different genera and 9 different species are obtained as probiotics. Among them, a strain named Lactobacillus planta-rum has obvious advantages in growth status, and there are related reports about its adjuvant therapeutic effect on depression-related mental illness, so we selected it as a probiotic strain for intervention experiments in follow-up studies.
In order to simulate the various depressive symptoms of people caused by social stress, this study selected the chronic social defeat mice depression model as the inter-vention subject. After the chronic social defeat stress model was established, the behav-ioral phenotype of the mice was evaluated using relevant behavioral tests. The results showed that the mice subjected to the social defeat stress showed significant social avoidance behaviors and significant desperate behavior, meanwhile, those stressed mice strikingly decreased social interest compared with the control mice indicating that the construction of depression model was successful.
Then we adopted a plan of constructing the chronic social defeat mice depression model and conducting treatment of probiotic at the same time, to explore the interven-tion effect of Lactobacillus plantarum on depression and its mechanism. The results showed that the intervention by gavage of Lactobacillus plantarum could significantly improve the behavioral phenotype of depression-like mice. The social avoidance be-havior of depressed mice decreased, and their social interest was significantly increased. In addition, desperate behavior of depressed mice improved significantly owing to the treatment of probiotic.
In order to explore the reasons why Lactobacillus plantarum could alleviate the behavioral phenotypes of depressed mice, we explored the intestinal microbiota and the inflammatory system. Through sequencing mouse fecal metagenomics and operating bioinformatics analysis, we found that compared with the control group, chronic social defeat stress could cause significant changes in the gut microbiota of depressed mice, including the diversity of intestinal flora increased, the diversity within the group de-creased, and the composition of the main microbiome changed. Thoes changes in bac-terial genera included 6 genera and 10 species.The treatment of Lactobacillus planta-rum could restore these bacteria imbalance caused by chronic social defeat to a certain extent, which implied that the intervention of Lactobacillus plantarum could alleviate the behavioral phenotypes of depressed mice by adjusting the intestinal ecosystem. The changes in the expression levels of related inflammatory cytokine were measured by RT-qPCR. The results found that Lactobacillus plantarum could significantly reduce the expression of highly activated inflammatory cytokine IL-1β, IL-2 and TNF-α in depressed mice indicating that Lactobacillus plantarum could alleviate the related phe notype of depressed mice by reducing inflammation activation.
Overall, we applied Lactobacillus plantarum to chronic social defeat stress mice depression model after the isolation and identification of the above-mentioned probiot-ics. We conducted the investigation among the behavioral phenotype, intestinal micro-biota and the inflammatory system in depressed mice. It revealed that Lactobacillus plantarum had a favorable effect on depression. The possible mechanism of treatment lays a theoretical foundation for the further promotion of the use of probiotics to assist in the treatment of depression and other mental illnesses. At the same time, this study also initially explores how probiotics affect the gut ecosystem and inflammation system, providing a case of the field of brain-gut axis study involving mental disorder. |
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