Center of Oxidative Stress Studies, Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre 90035-003, Brazil; Graduate Program in Biological Sciences: Biochemistry, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre 90035-003, Brazil; Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre 91501-970, Brazil.
Center of Oxidative Stress Studies, Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre 90035-003, Brazil.
J Nutr Biochem. 2024 Aug;130:109660. doi: 10.1016/j.jnutbio.2024.109660. Epub 2024 Apr 27.
Major depressive disorder (MDD) is a global health concern, affecting over 250 million individuals worldwide. In recent years, the gut-brain axis has emerged as a promising field for understanding the pathophysiology of MDD. Microbial metabolites, such as short-chain fatty acids (SCFAs)-acetate, butyrate, and propionate-, have gained attention for their potential to influence epigenetic modifications within the host brain. However, the precise mechanisms through which these metabolites participate in MDD pathophysiology remain elusive. This study was designed to investigate the effects of oral SCFA supplementation in adult male Wistar rats subjected to chronic unpredictable mild stress (CUMS). A subset of control and CUMS-exposed rats received different supplementations: sodium acetate (NaOAc) at a concentration of 60 mM, sodium butyrate (NaB) at 40 mM, sodium propionate (NaP) at 50 mM, or a mixture of these SCFAs. The gut microbiome was assessed through 16S rRNA sequencing, and epigenetic profiling was performed using Western blot analysis. Results demonstrated that NaP supplementation significantly alleviated anhedonia in stressed animals, as evidenced by improved performance in the sucrose consumption test. This ameliorative effect was potentially associated with the modulation of gut bacterial communities, accompanied by the attenuation of the region-specific epigenetic dysregulation in the brain of the animals exposed to chronic stress. These findings suggest a potential association between gut dysbiosis and stress response, and NaP could be a promising target for future MDD interventions. However, further studies are needed to fully elucidate the underlying mechanisms of these effects.
重度抑郁症（MDD）是一个全球性的健康问题，影响着全世界超过 2.5 亿人。近年来，肠道-大脑轴已成为理解 MDD 病理生理学的一个有前途的领域。微生物代谢产物，如短链脂肪酸（SCFAs）-醋酸盐、丁酸盐和丙酸盐，因其有可能影响宿主大脑中的表观遗传修饰而受到关注。然而，这些代谢产物参与 MDD 病理生理学的确切机制仍不清楚。本研究旨在探讨口服 SCFA 补充剂对慢性不可预测轻度应激（CUMS）成年雄性 Wistar 大鼠的影响。一部分对照和 CUMS 暴露的大鼠接受了不同的补充：浓度为 60mM 的醋酸钠（NaOAc）、40mM 的丁酸钠（NaB）、50mM 的丙酸钠（NaP）或这些 SCFAs 的混合物。通过 16S rRNA 测序评估肠道微生物组，通过 Western blot 分析进行表观遗传谱分析。结果表明，NaP 补充剂显著缓解了应激动物的快感缺失，这表现在蔗糖消耗测试中表现的改善。这种改善作用可能与肠道细菌群落的调节有关，同时伴随着慢性应激暴露动物大脑中特定区域的表观遗传失调的减弱。这些发现表明肠道微生物失调与应激反应之间存在潜在的关联，NaP 可能是未来 MDD 干预的一个有前途的靶点。然而，需要进一步的研究来充分阐明这些影响的潜在机制。
