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通过综合代谢谱分析揭示定殖小鼠盲肠的变化

Unraveling Cecal Alterations in Colonized Mice through Comprehensive Metabolic Profiling.

作者信息

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

机构信息

Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Biomic AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center B1.4, 10th km Thessaloniki-Thermi Road, GR 57001 Thessaloniki, Greece.

出版信息

J Proteome Res. 2024 Dec 6;23(12):5462-5475. doi: 10.1021/acs.jproteome.4c00578. Epub 2024 Oct 31.

Abstract

The disruption of gut microbiota caused by antibiotics favors the intestinal colonization of - a Gram-positive, spore-forming anaerobic bacterium that causes potentially fatal gastrointestinal infections. In an endeavor to elucidate the complexities of the gut-brain axis in the context of infection (CDI), a murine model has been used to investigate the potential effects of antibiotic administration and subsequent colonization by , as well as the impact of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the cecal metabolome for the first time. This follows our previous research which highlighted the metabolic effect of CDI and these treatments in the brain and employs the same four different metabolomics-based methods (targeted GC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted GC-MS). A total of 286 unique metabolites have been identified in the mouse cecal profiles and statistical analysis revealed that CDI, as well as the subsequent treatments, significantly alters cecal metabolites and lipids implicated in various biochemical pathways centered around amino acid metabolism, glycerophospholipid metabolism, and central carbon metabolism. To our knowledge, this study represents the first exploration of the effects of -induced colitis and potential treatments on the cecal tissue metabolome.

摘要

抗生素导致的肠道微生物群破坏有利于艰难梭菌(一种革兰氏阳性、形成孢子的厌氧细菌,可引起潜在致命的胃肠道感染)在肠道的定植。为了阐明艰难梭菌感染(CDI)背景下肠-脑轴的复杂性,首次使用小鼠模型研究抗生素给药及随后艰难梭菌定植的潜在影响,以及三种不同的10天治疗方法(甲硝唑、益生菌和粪便微生物群移植)对盲肠代谢组的影响。这延续了我们之前的研究,该研究突出了CDI及这些治疗方法在大脑中的代谢作用,并采用了相同的四种基于代谢组学的方法(靶向气相色谱-串联质谱法、靶向亲水相互作用色谱-串联质谱法、非靶向反相液相色谱-高分辨质谱/质谱法和非靶向气相色谱-质谱法)。在小鼠盲肠图谱中总共鉴定出286种独特的代谢物,统计分析表明,CDI以及随后的治疗方法显著改变了与围绕氨基酸代谢、甘油磷脂代谢和中心碳代谢的各种生化途径相关的盲肠代谢物和脂质。据我们所知,这项研究首次探索了艰难梭菌诱导的结肠炎及潜在治疗方法对盲肠组织代谢组的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73aa/11629376/ee0bdba85b3f/pr4c00578_0001.jpg

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