金枪鱼肽可通过调节肠道菌群和系统炎症及肠道5-HT水平改善小鼠抑郁样行为

Tuna peptide may improve depressive-like behavior of mice by regulating gut microbiota, systemic inflammation and intestinal 5-HT level

目的 考察金枪鱼肽对小鼠抑郁样行为的干预作用,并基于肠―脑轴初步解析金枪鱼肽的干预途径,为新一代抗抑郁食品或治疗剂的开发提供理论基础。方法 通过44 d慢性不可预知性温和应激造模建立抑郁小鼠模型,于造模第15天起,每日灌胃一定剂量金枪鱼肽,以蒸馏水为空白对照,鱼油为阳性对照。采用行为学指标评价小鼠抑郁样行为;分别采用酶联免疫法、鲎试剂法测定小鼠血清中炎症因子TNF-α、IL-1β、IL-2、IL-6及LPS水平;采用高效液相色谱―质谱法测定海马区、小肠组织和小鼠粪便中5-HT的水平;采用16SrRNA基因高通量测序和生物信息学方法考察小鼠粪便中肠道菌群组成变化。结果 与模型组相比,金枪鱼肽组小鼠抑郁样行为得到显著改善且优于鱼油组。经过金枪鱼肽干预后,模型小鼠血清中显著升高的炎症因子和LPS水平得以恢复,海马区和小肠组织中显著降低以及粪便中显著升高的5-HT水平也恢复到空白组的水平;显著下降的肠道菌群丰富度得以提高;肠道菌群B/F比值由模型组的1.58升高到6.61,基本恢复至空白组水平;模型组显著降低的Muribaculaceae丰度及显著升高的Bacteroides、Alistipes丰度均恢复至空白组水平。结论 金枪鱼肽可能通过调节肠道菌群和机体炎症及肠道5-HT水平改善慢性应激诱导的小鼠抑郁样行为,研究结果为金枪鱼肽开发成为新一代的绿色安全的抗抑郁食品提供了理论依据。

Objective To observe the intervention effect of tuna peptide on depression-like behavior in mice, and preliminarily analyze its intervention pathway based on the enteric-brain axis, so as to provide theoretical basis for the development of a new generation of antidepressant food or therapeutic agent. Methods The mouse model of depression was established through 44 d chronic unpredictable mild stress modeling. On the 15th day of modeling, a certain dose of tuna peptide(observation group), distilled water(blank control group) or fish oil(positive control group) was given intragastrically every day, respectively. The depression-like behavior of mice was evaluated using behavioral indexes. The levels of TNF-α, IL-1β, IL-2, IL-6 and LPS in serum of mice were determined with enzyme-linked immunoassay and Limulus lysate assay. High performance liquid chromatography-mass spectrometry was used to determine the contents of 5-HT in hippocampus, small intestine and feces of mice. The composition of gut microbiota in feces of mice was detected with 16S rRNA high-throughput sequencing and bioinformatics methods. Results Compared with the model group, tuna peptide significantly improved depression-like behavior, and the effect was better than fish oil. It significantly reduced the inflammatory factors and LPS in serum. Compared with model group, tuna peptide significantly increased the 5-HT content in hippocampus and small intestine, and decreased the 5-HT content in feces. Tuna peptide improved the richness of gut microbiota and the ratio of Bacteroidota/Firmicutes, and made them return to the levels in blank control group. Tuna peptide significantly increased the abundance of Muribaculaceae, decreased those of Bacteroides and Alistipes, and restored them to the levels in blank control group. Conclusion Tuna peptide may regulate gut microbiota, inflammation and intestinal 5-HT level to improve depressive-like behavior induced by chronic stress in mice. The results of this study provide a theoretical basis for the development of tuna peptide as a new generation of green and safe antidepressant food.