摄入高脂肪和高糖的西方饮食是导致大脑分子改变、认知功能障碍和神经退行性疾病的一个重要因素。因此，一个强制性的挑战是能够预防饮食引起的脑生理损伤的个性化策略。一种有前途的策略可能包括服用益生菌，已知益生菌可以通过肠-脑轴影响大脑功能。在这项研究中，我们探讨了基于罗伊氏柠檬酸杆菌 DSM 17938 (L. reuteri) 的方法是否可以抵消饮食引起的神经炎症、内质网应激 (ERS) 以及海马体（涉及学习和记忆的区域）的自噬。高脂肪和果糖饮食。西方饮食诱导了微生物群重塑，但罗伊氏乳杆菌既不调节这种变化，也不调节短链脂肪酸的血浆水平。有趣的是，促炎信号通路激活（NFkB 磷酸化增加，Toll 样受体 4、肿瘤坏死因子 α、白细胞介素 6、GFAP 和触珠蛋白数量增加）以及 ERS ​​激活（PERK 和 eif2α 增加）在西方饮食喂养的大鼠的海马中发现了磷酸化、较高的 C/EBP 同源蛋白量）和自噬（beclin、P62-sequestosome-1 和 LC3 II 增加）。所有这些海马的改变都可以通过罗伊氏乳杆菌的给药来预防，这首次显示了这种特定益生菌菌株的神经保护作用，主要归因于其调节西方饮食诱导的代谢性内毒素血症和全身炎症的能力，因为脂多糖、血浆水平降低。还发现了细胞因子和脂肪因子。基于使用罗伊氏乳杆菌 DSM17938 的治疗策略可能有益于逆转代谢综合征介导的脑功能障碍和认知能力下降。© 2024 作者。 BioFactors 由 Wiley periodicals LLC 代表国际生物化学和分子生物学联盟出版。

The consumption of western diets, high in fats and sugars, is a crucial contributor to brain molecular alterations, cognitive dysfunction and neurodegenerative diseases. Therefore, a mandatory challenge is the individuation of strategies capable of preventing diet-induced impairment of brain physiology. A promising strategy might consist in the administration of probiotics that are known to influence brain function via the gut-brain axis. In this study, we explored whether Limosilactobacillus reuteri DSM 17938 (L. reuteri)-based approach can counteract diet-induced neuroinflammation, endoplasmic reticulum stress (ERS), and autophagy in hippocampus, an area involved in learning and memory, in rat fed a high fat and fructose diet. The western diet induced a microbiota reshaping, but L. reuteri neither modulated this change, nor the plasma levels of short-chain fatty acids. Interestingly, pro-inflammatory signaling pathway activation (increased NFkB phosphorylation, raised amounts of toll-like receptor-4, tumor necrosis factor-alpha, interleukin-6, GFAP, and Haptoglobin), as well as activation of ERS (increased PERK and eif2α phosphorylation, higher C/EBP-homologous protein amounts) and autophagy (increased beclin, P62-sequestosome-1, and LC3 II) was revealed in hippocampus of western diet fed rats. All these hippocampal alterations were prevented by L. reuteri administration, showing for the first time a neuroprotective role of this specific probiotic strain, mainly attributable to its ability to regulate western diet-induced metabolic endotoxemia and systemic inflammation, as decreased levels of lipopolysaccharide, plasma cytokines, and adipokines were also found. Therapeutic strategies based on the use of L. reuteri DSM17938 could be beneficial in reversing metabolic syndrome-mediated brain dysfunction and cognitive decline.© 2024 The Author(s). BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.