Liu Zhipeng, Shi Shengchao, Zhang Xiaoyu, Wu Chao, Yang Qin, Ren Simeng, Shan Yujuan, Na Guanqiong
School of Public Health Wenzhou Medical University Wenzhou China.
Cixi Biomedical Research Institute Wenzhou Medical University Cixi China.
Food Sci Nutr. 2025 Jul 15;13(7):e70628. doi: 10.1002/fsn3.70628. eCollection 2025 Jul.
The conventional antidepressant treatments are ineffective, having undesirable side effects and relapse susceptibility. Nutrient and probiotics supplementation may have adjuvant antidepressant effects. This study aims to develop and assess the antidepressant properties of a nutrient-synbiotic complex and investigate the underlying mechanisms. We randomly divided into control, model, and four complex groups (nutrient, prebiotic, probiotic and united all components, respectively). We used lipopolysaccharide (LPS) to establish the depression model and assessed depressive-like behaviors using various behavioral tests, neuroplasticity, tryptophan pathway metabolites, and brain-derived neurotrophic factor (BDNF) in serum and prefrontal cortex (PFC). Intestinal microbiome analysis was performed using 16S rRNA gene sequencing. The nutrient-synbiotic complex presented beneficial effects against the depression-like behaviors induced by LPS, mitigated the increased level of kynurenine, and decreased levels of 5-hydroxytryptamine and BDNF both in serum and PFC ( < 0.05). It also reduced neuronal damage in PFC after LPS exposure ( < 0.05). Additionally, the nutrient-synbiotic complex effectively prevented the disturbance in abundance and diversity of the intestinal flora induced by LPS (Chao1: = 0.013, ACE: = 0.006, PCoA: = 0.25, = 0.003). A total of nine bacterial genera were negatively associated with depression, while eight were positively associated with depression. Among them, , , and showed significant intergroup differences ( < 0.05). This is the first study to demonstrate that a combined nutrient-synbiotic complex can prevent depressive-like behavioral changes induced by LPS. The underlying mechanisms may be associated with modifying the composition of the gut microbial community and improving the tryptophan metabolic homeostasis.
传统的抗抑郁治疗无效，且有不良副作用和复发易感性。补充营养素和益生菌可能具有辅助抗抑郁作用。本研究旨在开发和评估一种营养共生复合物的抗抑郁特性，并探究其潜在机制。我们随机分为对照组、模型组和四个复合物组（分别为营养素组、益生元组、益生菌组和所有成分联合组）。我们使用脂多糖（LPS）建立抑郁模型，并通过各种行为测试、神经可塑性、色氨酸途径代谢物以及血清和前额叶皮质（PFC）中的脑源性神经营养因子（BDNF）来评估抑郁样行为。使用16S rRNA基因测序进行肠道微生物群分析。营养共生复合物对LPS诱导的抑郁样行为具有有益作用，减轻了犬尿氨酸水平的升高，并降低了血清和PFC中5-羟色胺和BDNF的水平（<0.05）。它还减少了LPS暴露后PFC中的神经元损伤（<0.05）。此外，营养共生复合物有效预防了LPS诱导的肠道菌群丰度和多样性的紊乱（Chao1：=0.013，ACE：=0.006，PCoA： =0.2, =0.003）。共有9个细菌属与抑郁呈负相关，而8个与抑郁呈正相关。其中， 、 和 表现出显著的组间差异（<0.05）。这是第一项证明营养共生复合物组合可预防LPS诱导的抑郁样行为变化的研究。潜在机制可能与改变肠道微生物群落组成和改善色氨酸代谢稳态有关。
