Munteanu Constantin, Onose Gelu, Rotariu Mariana, Poștaru Mădălina, Turnea Marius, Galaction Anca Irina
Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy "Grigore T. Popa", 700454 Iasi, Romania.
Neuromuscular Rehabilitation Clinic Division, Clinical Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania.
Biomedicines. 2024 Nov 23;12(12):2670. doi: 10.3390/biomedicines12122670.
Microbiota-derived hydrogen sulfide (HS) plays a crucial role in modulating the gut-brain axis, with significant implications for neurodegenerative diseases such as Alzheimer's and Parkinson's. HS is produced by sulfate-reducing bacteria in the gut and acts as a critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, and immune responses. HS maintains gut barrier integrity at physiological levels and prevents systemic inflammation, which could impact neuroinflammation. However, as HS has a dual role or a Janus face, excessive HS production, often resulting from gut dysbiosis, can compromise the intestinal barrier and exacerbate neurodegenerative processes by promoting neuroinflammation and glial cell dysfunction. This imbalance is linked to the early pathogenesis of Alzheimer's and Parkinson's diseases, where the overproduction of HS exacerbates beta-amyloid deposition, tau hyperphosphorylation, and alpha-synuclein aggregation, driving neuroinflammatory responses and neuronal damage. Targeting gut microbiota to restore HS homeostasis through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation presents a promising therapeutic approach. By rebalancing the microbiota-derived HS, these strategies may mitigate neurodegeneration and offer novel treatments for Alzheimer's and Parkinson's diseases, underscoring the critical role of the gut-brain axis in maintaining central nervous system health.
微生物群衍生的硫化氢（HS）在调节肠-脑轴中起着关键作用，对阿尔茨海默病和帕金森病等神经退行性疾病具有重要意义。HS由肠道中的硫酸盐还原菌产生，作为一种关键的信号分子，通过多种途径影响大脑健康，包括调节炎症、氧化应激和免疫反应。HS在生理水平上维持肠道屏障的完整性，并预防可能影响神经炎症的全身炎症。然而，由于HS具有双重作用或两面性，通常由肠道菌群失调导致的HS过度产生会损害肠道屏障，并通过促进神经炎症和神经胶质细胞功能障碍加剧神经退行性过程。这种失衡与阿尔茨海默病和帕金森病的早期发病机制有关，其中HS的过度产生会加剧β-淀粉样蛋白沉积、tau蛋白过度磷酸化和α-突触核蛋白聚集，引发神经炎症反应和神经元损伤。通过饮食干预、益生菌、益生元以及粪便微生物群移植等方式靶向肠道微生物群以恢复HS的稳态，是一种很有前景的治疗方法。通过重新平衡微生物群衍生的HS，这些策略可能会减轻神经退行性变，并为阿尔茨海默病和帕金森病提供新的治疗方法，强调了肠-脑轴在维持中枢神经系统健康中的关键作用。
