该研究选用红笛鲷粗蛋白与低聚麦芽糖、低聚果糖和半乳低聚木糖组成的复合粉(PRSP)饲喂慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)模型小鼠,探究其预防抑郁样行为及机体相关损伤的作用。将80只小鼠平均分为空白对照组(CON)、模型组(CUMS)、氟西汀对照组(FLU)、复合粉干预组(PRSP)。模型组小鼠以CUMS进行42 d造模,造模同时给予部分小鼠灌胃1.8 g/(kg·d) PRSP,以10 mg/(kg·d)氟西汀为阳性对照。饲喂结束后对各组小鼠进行行为学测试、结肠切片苏木精-伊红染色和免疫组化染色观察、血清中内毒素(lipopolysaccharides,LPS)、D-乳酸(D-lactic acid,D-LA)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、IL-1β和IL-10含量测定、结肠内容物样本菌群高通量测序和生物信息学分析。CUMS造模引起了小鼠行为指标异常,结肠损伤评分升高,肠上皮黏液蛋白2表达显著降低,血清中D-LA、LPS、TNF-α、IL-1β和IL-6水平显著上升,CUMS组小鼠结肠内容物特有分类单元数目显著下降,厚壁菌门(Firmicutes)与拟杆菌门(Bacteroidetes)丰度之比显著升高,CUMS小鼠结肠中毛螺菌属(Lachnospiraceae)与罗氏菌属(Oscillibacter)丰度显著下降、另枝菌属(Alistipes)丰度显著上升,菌群谷氨酸、谷氨酰胺、酪氨酸、苏氨酸、半乳糖、果糖、蔗糖、麦芽糖代谢通路基因丰度显著升高,PRSP干预后上述指标均恢复到空白对照组水平。该复合粉可以抑制慢性应激诱发的小鼠结肠菌群结构紊乱及其特定的氨基酸和糖代谢异常升高,并阻止机体系统炎症及结肠损伤的发生,对抑郁样行为起到很好的预防作用,研究结果可为高效安全预防抑郁症的食物源产品的开发提供理论支撑。
In this work, chronic unpredictable mild stress (chronic unpredictable mild stress, CUMS) model mice were fed a composite powder containing Lutianus erythropterus crude protein with oligomaltose, oligofructose, and galacto-oligosaccharides (PRSP) to examine its potential to prevent depression-like behavior and organism-related injury.One hundred and eighty mice were split into four groups including an intervention group (PRSP), a model group (CUMS), a fluoxetine control group (FLU), and an empty control group (CON).For 42 days, the mice in the model group were subjected to CUMS modeling.At the same time as modeling, some animals received 1.8 g/(kg·d) PRSP via gavage, while a positive control group of mice received 10 mg/(kg·d) fluoxetine.Following the meal, behavioral evaluations, colon slice hematoxylin-eosin staining and immunohistochemical staining, serum lipopolysaccharides (LPS) levels, D-lactic acid (D-LA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-10, high-throughput sequencing, and bioinformatic analysis of colon content samples were performed in mice of each group.Mouse models subjected to CUMS modeling exhibited aberrant behavioral indices, higher colonic damage scores, markedly reduced expression of intestinal epithelial mucin-2 (MUC2), and markedly raised blood levels of D-LA, LPS, TNF-α, IL-1β, and IL-6.The CUMS group experienced a significant decrease in the number of taxonomic units unique to the contents of the colon.The Firmicutes had a much greater abundance ratio than Bacteroidetes overall.There was a significant decrease in the abundance of Lachnospiraceae and Oscillibacter and a significant increase in the abundance of Alistipes in the colon of CUMS mice.The abundance of colony glutamate, glutamine, tyrosine, threonine, galactose, fructose, sucrose, and maltose metabolic pathway genes was significantly increased, and all of the above indices were restored to the level of the empty control group after the PRSP intervention.The compound powder could inhibit the structural disorders of the colon flora of mice caused by chronic stress and its specific abnormal increase in amino acid and glucose metabolism, prevent the occurrence of systemic inflammation and colon damage in the body, and play a good preventive role in depression-like behavior, and the results of the study can provide theoretical support for the development of efficient and safe food for the prevention of depression.
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