Nohesara Shabnam, Mostafavi Abdolmaleky Hamid, Pirani Ahmad, Thiagalingam Sam
Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Cells. 2025 Jul 4;14(13):1027. doi: 10.3390/cells14131027.
Neuroinflammation is a hallmark of many neuropsychiatric disorders (NPD), which are among the leading causes of disability worldwide. Emerging evidence highlights the significant role of the gut microbiota (GM)-immune system-brain axis in neuroinflammation and the pathogenesis of NPD, primarily through epigenetic mechanisms. Gut microbes and their metabolites influence immune cell activity and brain function, thereby contributing to neuroinflammation and the development and progression of NPD. The enteric nervous system, the autonomic nervous system, neuroendocrine signaling, and the immune system all participate in bidirectional communication between the gut and the brain. Importantly, the interaction of each of these systems with the GM influences epigenetic pathways. Here, we first explore the intricate relationship among intestinal microbes, microbial metabolites, and immune cell activity, with a focus on epigenetic mechanisms involved in NPD pathogenesis. Next, we provide background information on the association between inflammation and epigenetic aberrations in the context of NPD. Additionally, we review emerging therapeutic strategies-such as prebiotics, probiotics, methyl-rich diets, ketogenic diet, and medications-that may modulate the GM-immune system-brain axis via epigenetic regulation for the prevention or treatment of NPD. Finally, we discuss the challenges and future directions in investigating the critical role of this axis in mental health.
神经炎症是许多神经精神疾病（NPD）的一个标志，这些疾病是全球致残的主要原因之一。新出现的证据突出了肠道微生物群（GM）-免疫系统-脑轴在神经炎症和NPD发病机制中的重要作用，主要是通过表观遗传机制。肠道微生物及其代谢产物影响免疫细胞活性和脑功能，从而导致神经炎症以及NPD的发生和发展。肠神经系统、自主神经系统、神经内分泌信号传导和免疫系统都参与肠道与大脑之间的双向通信。重要的是，这些系统中的每一个与GM的相互作用都会影响表观遗传途径。在这里，我们首先探讨肠道微生物、微生物代谢产物和免疫细胞活性之间的复杂关系，重点关注NPD发病机制中涉及的表观遗传机制。接下来，我们提供关于NPD背景下炎症与表观遗传异常之间关联的背景信息。此外，我们综述了新兴的治疗策略，如益生元、益生菌、富含甲基的饮食、生酮饮食和药物，这些策略可能通过表观遗传调控来调节GM-免疫系统-脑轴，以预防或治疗NPD。最后，我们讨论了研究该轴在心理健康中的关键作用所面临的挑战和未来方向。
