Dilmore Amanda H, McDonald Daniel, Nguyen Tanya T, Adams James B, Krajmalnik-Brown Rosa, Elijah Emmanuel, Dorrestein Pieter C, Knight Rob
Department of Pediatrics, School of Medicine, University of California, San Diegogrid.266100.3, San Diego, California, USA.
Department of Psychiatry, UC San Diego, San Diego, California, USA.
mSystems. 2021 Dec 21;6(6):e0100621. doi: 10.1128/mSystems.01006-21. Epub 2021 Nov 30.
Alterations to the gut microbiome have been reported between children with autism spectrum disorders (ASDs) and typically developing (TD) children. Characterizing these differences has led to the proposal of new treatments for ASD, such as probiotic interventions and fecal matter transplants. However, no study to date has characterized the gut microbiome or metabolome in Pitt Hopkins syndrome (PTHS), a severe ASD with a high incidence of gastrointestinal (GI) disturbances such as constipation. Here, we surveyed the gut microbiome and metabolome in a cohort of PTHS individuals and their unaffected parents. We focused our analysis on Clostridium bolteae, a microbe previously associated with ASD known to chemically modify bile acids in the gut. PTHS individuals carry a higher load of C. bolteae than their parents as well as both ASD and non-ASD individuals from the American Gut Project cohort. Specific metabolites were associated with PTHS, including bile acids and sphingosines. With a metadata reanalysis tool, we found that PTHS-associated metabolites have previously been identified in inflammatory bowel disease and obesity patients. These results suggest microbial involvement in PTHS, but further research must be performed to clarify the exact mechanisms through which microbes may act. Furthermore, new associations between PTHS-specific metabolites and other conditions may lead to additional therapeutic options for PTHS individuals. GI disturbances in ASD such as severe constipation can be medically significant and often require medication. This is especially true for individuals with PTHS, suggesting that the gut microbiome may be involved in PTHS's pathology. Revealing associations between specific gut microbes and PTHS may allow the development of new therapeutics or the application of existing therapeutics to ease day-to-day challenges encountered by PTHS individuals. In this study, we characterized an association between and PTHS, in addition to metabolites linked to both PTHS and . We also identified other microbiome-involved medical conditions where PTHS-associated metabolites have been isolated. Utilizing common metabolites to identify conditions with similar phenotypes may suggest new therapeutic options for GI-related symptoms.
据报道，自闭症谱系障碍（ASD）儿童与发育正常（TD）儿童的肠道微生物群存在差异。对这些差异的特征描述促使人们提出了针对ASD的新治疗方法，如益生菌干预和粪便移植。然而，迄今为止，尚无研究对皮特·霍普金斯综合征（PTHS）的肠道微生物群或代谢组进行特征描述，PTHS是一种严重的ASD，胃肠道（GI）紊乱（如便秘）的发生率很高。在此，我们对一组PTHS个体及其未受影响的父母的肠道微生物群和代谢组进行了调查。我们将分析重点放在了梭状芽孢杆菌属（Clostridium bolteae）上，这是一种先前与ASD相关的微生物，已知其可在肠道中对胆汁酸进行化学修饰。与美国肠道计划队列中的父母以及ASD和非ASD个体相比，PTHS个体携带的博氏梭菌（C. bolteae）负荷更高。特定的代谢产物与PTHS相关，包括胆汁酸和鞘氨醇。通过元数据分析工具，我们发现先前在炎症性肠病和肥胖症患者中已鉴定出与PTHS相关的代谢产物。这些结果表明微生物与PTHS有关，但必须进行进一步研究以阐明微生物可能发挥作用的确切机制。此外，PTHS特异性代谢产物与其他病症之间的新关联可能会为PTHS个体带来更多治疗选择。ASD中的胃肠道紊乱，如严重便秘，在医学上可能具有重要意义，通常需要药物治疗。对于PTHS个体尤其如此，这表明肠道微生物群可能参与了PTHS的病理过程。揭示特定肠道微生物与PTHS之间的关联可能有助于开发新的治疗方法或应用现有治疗方法来缓解PTHS个体日常遇到的挑战。在本研究中，我们除了表征了与PTHS相关的代谢产物外，还描述了一种与PTHS的关联。我们还确定了其他涉及微生物群的病症，在这些病症中已分离出与PTHS相关的代谢产物。利用常见的代谢产物来识别具有相似表型的病症可能会为胃肠道相关症状提供新的治疗选择。
