Environment, Commonwealth Scientific and Industrial Research Organization, Ecosciences Precinct, Dutton Park, QLD 4102, Australia.
Department of Chemistry and Biotechnology, School of Science, Computing and Engineering Technologies, Swinburne University of Technology, Hawthorn, VIC 3122, Australia.
Int J Mol Sci. 2023 Jan 13;24(2):1636. doi: 10.3390/ijms24021636.
Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mechanisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to and uropathogenic (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duodenum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatography-mass spectrometry, respectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were significantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and the redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration indicated that populations of three bacterial families- (Up), (Up), and (Down)-were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.
类锥体寄生虫感染，如贾第虫病和隐孢子虫病，对相当一部分人类和商业牲畜群体产生负面影响。尽管如此，疾病的分子机制，特别是对胃肠道以外的身体的影响，仍未得到充分理解。为了突出宿主-寄生虫-微生物组生化相互作用，我们在贾第虫病的 C57BL/6J 小鼠模型中利用整合代谢组学-16S rRNA 基因组学和代谢组学-蛋白质组学方法，并将这些方法与尿路感染性 （UPEC） 感染进行了比较。在感染后 10 天收集了全面的样本（粪便、血液、肝脏和十二指肠、空肠、回肠、盲肠和结肠的腔内容物），并分别通过液相和气相色谱-质谱法进行蛋白质组和代谢组分析。使用 16S rRNA 宏基因组学检测粪便和腔冲洗液中的微生物群。蛋白质组-代谢组分析表明，与其他感染相比，在贾第虫病期间，肠道和肝脏中分别有 12 个和 16 个关键途径发生了显著变化。在贾第虫病期间，肠道腔内容物和肝脏中的糖酵解和支持乙醛酸和二羧酸代谢的途径以及谷胱甘肽代谢的氧化还原途径等能量途径上调。代谢组学-16S rRNA 遗传学整合表明，在贾第虫病期间，三个细菌家族的种群- （上升）、 （上升）和 （下降）-在整个肠道中受到的影响最大，导致糖酵解和短链脂肪酸（SCFA）代谢上调。特别是，扰乱的 种群似乎沿着肠道-肝脏轴引起氧化应激反应。总体而言，本研究应用的系统生物学方法强调，宿主-寄生虫-微生物组生化相互作用的影响不仅局限于肠道生态系统，还延伸到肠道-肝脏轴。这些发现是全面比较的第一步，以确定宿主-寄生虫相互作用的主要分子和生化贡献，并为类锥体寄生虫感染的生物标志物发现和精准健康解决方案的发展做出贡献。
