Microbial determinants of dementia risk in subjects of Mexican descent with type 2 diabetes living in South Texas.
Microbial determinants of dementia risk in subjects of Mexican descent with type 2 diabetes living in South Texas.
复制标题
生活在德克萨斯州南部的墨西哥裔 2 型糖尿病患者痴呆风险的微生物决定因素。
DOI：
10.1101/2024.03.20.24304637
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Buffington,ShellyA
中科院分区：
文献类型：
--
作者：
Matz,LisaM;Shah,NisargS;Porterfield,Laura;Stuyck,OliviaM;Jochum,MichaelD;Kayed,Rakez;Taglialatela,Giulio;Urban,RandallJ;Buffington,ShellyA
2型糖尿病(T2D)是包括阿尔茨海默病(AD)在内的神经变性和痴呆的常见先兆，但其潜在机制仍未解决。居住在德克萨斯州南部的墨西哥裔个体增加了T2D和早发性AD的共病患病率，尽管易感APOE-e4变异的发生率很低，而且居住在墨西哥的亲属中没有表型-这表明环境因素在T2D和AD易感性的重合中发挥了作用。在这里，在一项小型临床试验中，我们表明人类肠道微生物群的失调可能会导致这一人群的神经炎症和AD风险。不同的胃肠道症状评定量表(GSRs)的反应，尽管在表达的饮食偏好没有差异，提供了T2D受试者(ST2D)与人群匹配的健康对照组(HC)之间肠道微生物生态改变的第一证据。参与者粪便的Metataxonomic 16S rRNA测序显示，sT2D与HC肠道群落的α多样性降低，并确定BMI是肠道群落结构的驱动因素。线性判别分析效应大小(Lefse)表明，在sT2D肠道微生物区系中，产生短链脂肪酸的类群Lachnospiraceae、Faecaliens和Alistipe的相对丰度显著降低，而致病杆菌Escherichia-Shigella、Enterbacter和Clostridia Innocuum的相对丰度增加，以及差异丰富的基因和代谢途径。这些结果表明，对T2D患者肠道微生物群的特征可以确定“疾病状态”微生物群中的关键因素，这些微生物群可能会增加神经变性的风险或加速神经变性的发生。此外，他们确定了预防和治疗阿尔茨海默病神经炎症的候选微生物组靶向方法。
Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and dementia, including Alzheimer’s Disease (AD), yet the underlying mechanisms remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the predisposing APOE-e4 variant and an absence of the phenotype among relatives residing in Mexico – suggesting a role for environmental factors in coincident T2D and AD susceptibility. Here, in a small clinical trial, we show dysbiosis of the human gut microbiome could contribute to neuroinflammation and risk for AD in this population. Divergent Gastrointestinal Symptom Rating Scale (GSRS) responses, despite no differences in expressed dietary preferences, provided the first evidence for altered gut microbial ecology among T2D subjects (sT2D) versus population-matched healthy controls (HC). Metataxonomic 16S rRNA sequencing of participant stool revealed a decrease in alpha diversity of sT2D versus HC gut communities and identified BMI as a driver of gut community structure. Linear discriminant analysis effect size (LEfSe) identified a significant decrease in the relative abundance of the short-chain fatty acid-producing taxa Lachnospiraceae, Faecalibacterium, and Alistipes and an increase in pathobionts Escherichia-Shigella, Enterobacter, and Clostridia innocuum among sT2D gut microbiota, as well as differentially abundant gene and metabolic pathways. These results suggest characterization of the gut microbiome of individuals with T2D could identify key actors among “disease state” microbiota which may increase risk for or accelerate the onset of neurodegeneration. Furthermore, they identify candidate microbiome-targeted approaches for prevention and treatment of neuroinflammation in AD.