粪便短链脂肪酸因性别和淀粉样蛋白状态而异。
Fecal Short-Chain Fatty Acids Vary by Sex and Amyloid Status.
作者信息
Kuehn Jessamine F, Zhang Qijun, Heston Margo B, Kang Jea Woo, Harding Sandra J, Davenport-Sis Nancy J, Peter Darby C, Kerby Robert L, Vemuganti Vaibhav, Schiffmann Emma C, Tallon Michael M, Harpt Joseph, Hajra Arun, Wheeler J L, Shankar Sushma, Mickol Alissa, Zemberi Justus, Chow Hana, Zhang Eric, Clements Eleanor, Noughani Hanna, Forst Allison, Everitt Grace, Kollmorgen Gwendlyn, Quijano-Rubio Clara, Christian Bradley T, Carlsson Cynthia M, Johnson Sterling C, Asthana Sanjay, Zetterberg Henrik, Blennow Kaj, Ulland Tyler K, Rey Federico E, Bendlin Barbara B
出版信息
medRxiv. 2025 Aug 1:2025.07.31.25332523. doi: 10.1101/2025.07.31.25332523.
INTRODUCTION
Short-chain fatty acids (SCFAs), produced by gut microbes, influence Alzheimer's disease (AD) pathology in animals. Less is known about SCFAs and AD in humans. We profiled feces of adults along the AD continuum to investigate gut microbiome and SCFA associations with AD pathology and cognition.
METHODS
We measured SCFAs and bacterial abundances in fecal samples from 287 participants in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention. We performed regressions examining associations between SCFAs or gut microbes and AD pathology and cognition.
RESULTS
Fecal propionate, isovalerate, and propionate-producing bacteria are inversely associated with amyloid status. Mediation analysis found that propionate mediates sex-specific associations between SCFAs and CSF biomarkers. SCFA levels are associated with slower cognitive decline.
DISCUSSION
These results link SCFAs and propionate-producing bacteria with AD. This may inform efforts to leverage diet and specific bacteria to boost SCFA production and potentially ameliorate AD progression.
引言
肠道微生物产生的短链脂肪酸（SCFA）会影响动物的阿尔茨海默病（AD）病理。关于人类体内的SCFA与AD的关系，人们了解得较少。我们对处于AD病程连续阶段的成年人粪便进行了分析，以研究肠道微生物群以及SCFA与AD病理和认知之间的关联。
方法
我们测量了威斯康星州阿尔茨海默病研究中心和威斯康星州阿尔茨海默病预防登记处287名参与者粪便样本中的SCFA和细菌丰度。我们进行了回归分析，以检验SCFA或肠道微生物与AD病理和认知之间的关联。
结果
粪便中的丙酸、异戊酸以及产生丙酸的细菌与淀粉样蛋白状态呈负相关。中介分析发现，丙酸介导了SCFA与脑脊液生物标志物之间的性别特异性关联。SCFA水平与认知能力下降较慢有关。
讨论
这些结果将SCFA和产生丙酸的细菌与AD联系起来。这可能为利用饮食和特定细菌来促进SCFA生成并潜在改善AD进展的研究提供参考。
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