Cho Hyunji, Park Yongsoon
Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea.
Probiotics Antimicrob Proteins. 2024 Sep 7. doi: 10.1007/s12602-024-10332-1.
Probiotics, postbiotics, and n-3 polyunsaturated fatty acids (PUFA) have antidepressant-like effects. However, the underlying mechanisms of the dopaminergic pathway are unclear. The present study investigated the hypothesis that probiotics and postbiotics combined with n-3 PUFA synergistically improve depression by modulating the dopaminergic pathway through the brain-gut axis. Rats were randomly divided into seven groups: non-chronic mild stress (CMS) with n-6 PUFA, and CMS with n-6 PUFA, n-3 PUFA, probiotics, postbiotics, probiotics combined with n-3 PUFA, and postbiotics combined with n-3 PUFA. Probiotics, postbiotics, and n-3 PUFA improved depressive behaviors, decreased blood concentrations of interferon-γ, and interleukin-1β, and increased the brain and gut concentrations of short chain fatty acids and dopamine. Moreover, probiotics, postbiotics, and n-3 PUFA increased the brain and gut expression of glucocorticoid receptor and tyrosine hydroxylase; brain expression of l-type amino acid transporter 1 and dopamine receptor (DR) D1; and gut expression of DRD2. The expression of phosphorylated protein kinase A/protein kinase A and phosphorylated cAMP response element-binding protein/cAMP response element-binding protein increased in the brain, however, decreased in the gut by the supplementation of probiotics, postbiotics, and n-3 PUFA. There was synergistic effect of probiotics and postbiotics combined with n-3 PUFA on the depressive behaviors and dopaminergic pathway in blood, brain, and gut. Moreover, no significant difference in the dopaminergic pathways between the probiotics and postbiotics was observed. In conclusion, probiotics and postbiotics, combined with n-3 PUFA have synergistic antidepressant-like effects on the dopaminergic pathway through the brain-gut axis in rats exposed to CMS.
益生菌、后生元及n-3多不饱和脂肪酸（PUFA）具有抗抑郁样作用。然而，多巴胺能通路的潜在机制尚不清楚。本研究调查了以下假设：益生菌、后生元与n-3 PUFA联合通过脑-肠轴调节多巴胺能通路，协同改善抑郁。将大鼠随机分为七组：非慢性轻度应激（CMS）+n-6 PUFA组，以及CMS+n-6 PUFA组、n-3 PUFA组、益生菌组、后生元组、益生菌联合n-3 PUFA组和后生元联合n-3 PUFA组。益生菌、后生元及n-3 PUFA改善了抑郁行为，降低了血液中γ-干扰素和白细胞介素-1β的浓度，并增加了大脑和肠道中短链脂肪酸和多巴胺的浓度。此外，益生菌、后生元及n-3 PUFA增加了大脑和肠道中糖皮质激素受体和酪氨酸羟化酶的表达；大脑中L型氨基酸转运体1和多巴胺受体（DR）D1的表达；以及肠道中DRD2的表达。补充益生菌、后生元及n-3 PUFA后，大脑中磷酸化蛋白激酶A/蛋白激酶A和磷酸化环磷酸腺苷反应元件结合蛋白/环磷酸腺苷反应元件结合蛋白的表达增加，而肠道中的表达降低。益生菌、后生元与n-3 PUFA联合对血液、大脑和肠道中的抑郁行为和多巴胺能通路有协同作用。此外，未观察到益生菌和后生元在多巴胺能通路上的显著差异。总之，在暴露于CMS的大鼠中，益生菌、后生元与n-3 PUFA联合通过脑-肠轴对多巴胺能通路具有协同抗抑郁样作用。
