Chu Xixia, Hou Yujun, Meng Qiong, Croteau Deborah L, Wei Yong, De Supriyo, Becker Kevin G, Bohr Vilhelm A
DNA Repair Section, National Institute on Aging, Baltimore, MD, United States.
Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Front Aging Neurosci. 2022 Sep 15;14:993615. doi: 10.3389/fnagi.2022.993615. eCollection 2022.
Alzheimer's disease (AD) is the most common neurodegenerative disease. Growing evidence suggests an important role for gut dysbiosis and gut microbiota-host interactions in aging and neurodegeneration. Our previous works have demonstrated that supplementation with the nicotinamide adenine dinucleotide (NAD) precursor, nicotinamide riboside (NR), reduced the brain features of AD, including neuroinflammation, deoxyribonucleic acid (DNA) damage, synaptic dysfunction, and cognitive impairment. However, the impact of NR administration on the intestinal microbiota of AD remains unknown. In this study, we investigated the relationship between gut microbiota and NR treatment in APP/PS1 transgenic (AD) mice. Compared with wild type (WT) mice, the gut microbiota diversity in AD mice was lower and the microbiota composition and enterotype were significantly different. Moreover, there were gender differences in gut microbiome between female and male AD mice. After supplementation with NR for 8 weeks, the decreased diversity and perturbated microbial compositions were normalized in AD mice. This included the species , , , , , , , , and . Our results indicate an interplay between NR and host-microbiota in APP/PS1 mice, suggesting that the effect of NR on gut dysbiosis may be an important component in its therapeutic functions in AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病。越来越多的证据表明，肠道菌群失调以及肠道微生物群与宿主的相互作用在衰老和神经退行性变中起重要作用。我们之前的研究表明，补充烟酰胺腺嘌呤二核苷酸（NAD）前体烟酰胺核糖（NR）可减轻AD的脑部特征，包括神经炎症、脱氧核糖核酸（DNA）损伤、突触功能障碍和认知障碍。然而，NR给药对AD肠道微生物群的影响尚不清楚。在本研究中，我们调查了APP/PS1转基因（AD）小鼠肠道微生物群与NR治疗之间的关系。与野生型（WT）小鼠相比，AD小鼠的肠道微生物群多样性较低，微生物群组成和肠型存在显著差异。此外，雌性和雄性AD小鼠的肠道微生物组存在性别差异。用NR补充8周后，AD小鼠中降低的多样性和受干扰的微生物组成恢复正常。这包括 、 、 、 、 、 、 、 和 等物种。我们的结果表明NR与APP/PS1小鼠宿主微生物群之间存在相互作用，提示NR对肠道菌群失调的影响可能是其在AD治疗功能中的重要组成部分。
