School of Public Health, Dali University, China.
Dali Lesson Dairy Co. Ltd., Dali, China.
Microbiol Res. 2024 Jan;278:127547. doi: 10.1016/j.micres.2023.127547. Epub 2023 Nov 11.
This study aims to investigate the protective effect of a freeze-dried powder prepared from a fermentation milk whey containing a high-yield GABA strain (FDH-GABA) against D-galactose-induced brain injury and gut microbiota imbalances in mice by probing changes to the PI3K/AKT/mTOR signaling pathway. A prematurely aged mouse model was established by performing the subcutaneous injection of D-galactose. Subsequently, the effects of FDH-GABA on the nervous system and intestinal microenvironment of the mice were explored by measuring their antioxidant activities, anti-inflammatory state, autophagy, pathway-related target protein expression levels, and intestinal microorganisms. Compared to the D-gal group, FDH-GABA improved the levels of SOD, T-AOC, IL-10, and neurotransmitters, while it reduced the contents of MDA and TNF-α. FDH-GABA also promoted autophagy and inhibited the PI3K/AKT/mTOR signaling pathway in the brains of the aged mice. Moreover, FDH-GABA restored the diversity of their intestinal flora. Pathological observations indicated that FDH-GABA was protective against damage to the brain and intestine of D-galactose-induced aging mice. These results reveal that FDH-GABA not only improved antioxidant stress, attenuated inflammation, restored the neurotransmitter content, and protected the tissue structure of the intestine and brain, but also effectively improved their intestinal microenvironment. The ameliorative effect of FDH-GABA on premature aging showed a clear dose-response relationship, and at the same time, the changes of intestinal microorganisms showed a certain correlation with the relevant indexes of nervous system. These findings provide insight into the effect of the FDH-GABA intervention on aging, providing a novel means for alleviating detrimental neurodegenerative changes in the aging population.
本研究旨在探讨一种由富含高产量 GABA 菌株的发酵乳清制备的冻干粉末（FDH-GABA）对 D-半乳糖诱导的脑损伤和肠道微生物失衡的保护作用，通过探究 PI3K/AKT/mTOR 信号通路的变化。通过皮下注射 D-半乳糖建立早衰小鼠模型。随后，通过测量抗氧化活性、抗炎状态、自噬、相关通路靶蛋白表达水平和肠道微生物，研究 FDH-GABA 对小鼠神经系统和肠道微环境的影响。与 D-gal 组相比，FDH-GABA 提高了 SOD、T-AOC、IL-10 和神经递质的水平，同时降低了 MDA 和 TNF-α的含量。FDH-GABA 还促进了衰老小鼠大脑中的自噬并抑制了 PI3K/AKT/mTOR 信号通路。此外，FDH-GABA 恢复了其肠道菌群的多样性。病理学观察表明，FDH-GABA 对 D-半乳糖诱导的衰老小鼠的脑和肠损伤具有保护作用。这些结果表明，FDH-GABA 不仅改善了抗氧化应激、减轻了炎症、恢复了神经递质含量、保护了肠和脑组织的结构，而且还有效地改善了其肠道微环境。FDH-GABA 对早衰的改善作用呈现出明显的剂量反应关系，同时，肠道微生物的变化与神经系统的相关指标表现出一定的相关性。这些发现为 FDH-GABA 干预衰老的效果提供了深入了解，为缓解衰老人群中有害的神经退行性变化提供了一种新的手段。
