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    • Olga Deda,Melina Kachrimanidou,Emily G. Armitage,Thomai Mouskeftara,Neil J. Loftus,Ioannis Zervos,Ioannis Taitzoglou,Helen Gika

    METABOLITES（2022）

    Aristotle Univ Thessaloniki | Shimadzu Co Ltd

    Cited 3|Views19
    Abstract
    Clostridioides difficile infection (CDI) is responsible for an increasing number of cases of post-antibiotic diarrhea worldwide, which has high severity and mortality among hospitalized elderly patients. The disruption of gut microbiota due to antibacterial medication facilitates the intestinal colonization of C. difficile. In the present study, a murine model was used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the effects of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the brain metabolome for the first time. Four different metabolomic-based methods (targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS, targeted GC-MS/MS, and untargeted GC-MS) were applied, resulting in the identification of 217 unique metabolites in the brain extracts, mainly glycerophos-pholipids, glycerolipids, amino acids, carbohydrates, and fatty acids. Univariate and multivariate statistical analysis revealed that CDI, as well as the subsequent treatments, altered significantly several brain metabolites, probably due to gut dysbiosis, and affected the brain through the gut-brain axis. Notably, none of the therapeutic approaches completely restored the brain metabolic profile to the original, healthy, and non-infected phenotype, even after 10 days of treatment.
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    Clostridioides difficile,mice,antibiotics,FMT,metabolic profiling,metabolomics,LC-MS,GC-MS,brain
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    • Pretraining has recently greatly promoted the development of natural language processing (NLP)
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    【要点】：本研究首次利用小鼠模型探讨了抗生素治疗和随后的C. difficile定植以及三种不同10天治疗（甲硝唑、益生菌和粪便微生物群移植）对大脑代谢组的影响，揭示了C. difficile感染及其治疗通过肠-脑轴影响大脑的机制，并发现即使经过10天治疗，这些治疗方法也无法完全恢复大脑代谢组到健康非感染状态。
    

    【方法】：本研究采用了四种不同的基于代谢组学的方法（目标HILIC-MS/MS、非目标RP-LC-HRMS/MS、目标GC-MS/MS和非目标GC-MS）对大脑提取物进行分析，共鉴定出217种独特的代谢物。
    

    【实验】：通过建立小鼠模型，研究了抗生素治疗及其后续C. difficile定植对大脑代谢组的影响，并对比了三种不同的治疗措施（甲硝唑、益生菌和粪便微生物群移植）。结果显示，这些治疗方法都无法完全恢复大脑代谢组至健康非感染状态。