Sekera Emily R, Rudolph Heather L, Carro Stephen D, Morales Michael J, Bett Glenna C L, Rasmusson Randall L, Wood Troy D
Department of Chemistry, Natural Sciences Complex, University at Buffalo, State University of New York, Buffalo, NY.
Department of Physiology and Biophysics, University at Buffalo, State University of New York, Buffalo, NY.
Metabolomics. 2017 Nov;13(11). doi: 10.1007/s11306-017-1277-9. Epub 2017 Oct 3.
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders lacking a clinical biomarker for diagnosis. Emerging evidence shows that intestinal microflora from ASD subjects can be distinguished from controls, suggesting metabolite differences due to the action of intestinal microbes may provide a means for identifying potential biomarkers for ASD.
The aim of this study was to determine if quantitative differences in levels of stercobilin and stercobilinogen, metabolites produced by biological action of intestinal microflora, exist in the fecal matter between an ASD mouse model population and controls.
Pairs of fecal samples were collected from two mouse groups, an ASD model group with Timothy syndrome 2 (TS2-NEO) and a gender-matched control group. After centrifugation, supernatant was spiked with an O-labeled stercobilin isotopomer and subjected to solid phase extraction for processing. Extracted samples were spotted on a stainless steel plate and subjected to matrix-assisted laser desorption and ionization mass spectrometry using dihydroxybenzoic acid as the matrix ( = 5). Peak areas for bilins and O-stercobilin isotopomers were determined in each fecal sample.
A 40-45% depletion in stercobilin in TS2-NEO fecal samples compared with controls was observed with p < 0.05; a less dramatic depletion was observed for stercobilinogen.
The results show that stercobilin depletion in feces is observed for an ASD mouse model vs. controls. This may help to explain recent observations of a less diverse microbiome in humans with ASD and may prove helpful in developing a clinical ASD biomarker.
自闭症谱系障碍(ASD)是一组缺乏临床诊断生物标志物的神经发育障碍。新出现的证据表明,自闭症谱系障碍患者的肠道微生物群与对照组不同,这表明肠道微生物作用导致的代谢物差异可能为识别自闭症谱系障碍的潜在生物标志物提供一种方法。
本研究的目的是确定在自闭症谱系障碍小鼠模型群体和对照组的粪便中,是否存在由肠道微生物生物作用产生的代谢物粪胆素和粪胆原水平的定量差异。
从两组小鼠中收集粪便样本,一组是患有蒂莫西综合征2(TS2-NEO)的自闭症谱系障碍模型组,另一组是性别匹配的对照组。离心后,向上清液中加入O标记的粪胆素同位素异构体,然后进行固相萃取处理。将提取的样品点在不锈钢板上,以二羟基苯甲酸为基质(=5)进行基质辅助激光解吸电离质谱分析。测定每个粪便样本中胆素和O-粪胆素同位素异构体的峰面积。
与对照组相比,TS2-NEO粪便样本中粪胆素减少了40-45%,p<0.05;粪胆原的减少幅度较小。
结果表明,与对照组相比,自闭症谱系障碍小鼠模型的粪便中粪胆素减少。这可能有助于解释最近在自闭症谱系障碍患者中观察到的微生物群多样性较低的现象,并可能有助于开发自闭症谱系障碍的临床生物标志物。