Urinary markers of Mycobacterium tuberculosis and dysbiosis in paediatric tuberculous meningitis cases undergoing treatment.

IF 4.3 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gut Pathogens Pub Date : 2024-03-12 DOI:10.1186/s13099-024-00609-9

Simon Isaiah, Du Toit Loots, A Marceline Tutu van Furth, Elmarie Davoren, Sabine van Elsland, Regan Solomons, Martijn van der Kuip, Shayne Mason

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Abstract

Background: The pathogenesis of tuberculous meningitis (TBM) involves infection by Mycobacterium tuberculosis in the meninges and brain. However, recent studies have shown that the immune response and inflammatory processes triggered by TBM can have significant effects on gut microbiota. Disruptions in the gut microbiome have been linked to various systemic consequences, including altered immunity and metabolic dysregulation. Inflammation caused by TBM, antibiotic treatment, and changes in host immunity can all influence the composition of gut microbes. This complex relationship between TBM and the gut microbiome is of great importance in clinical settings. To gain a deeper understanding of the intricate interactions between TBM and the gut microbiome, we report innovative insights into the development of the disease in response to treatment. Ultimately, this could lead to improved outcomes, management strategies and quality of life for individuals affected by TBM.

Method: We used a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to investigate metabolites associated with gut metabolism in paediatric participants by analysing the urine samples collected from a control group (n = 40), and an experimental group (n = 35) with confirmed TBM, which were subdivided into TBM stage 1 (n = 8), stage 2 (n = 11) and stage 3 (n = 16).

Findings: Our metabolomics investigation showed that, of the 78 initially selected compounds of microbiome origin, eight unique urinary metabolites were identified: 2-methylbutyrlglycine, 3-hydroxypropionic acid, 3-methylcrotonylglycine, 4-hydroxyhippuric acid, 5-hydroxyindoleacetic acid, 5-hydroxyhexanoic acid, isobutyrylglycine, and phenylacetylglutamine as urinary markers of dysbiosis in TBM.

Conclusion: These results - which are supported by previous urinary studies of tuberculosis - highlight the importance of gut metabolism and of identifying corresponding microbial metabolites as novel points for the foundation of improved management of TBM patients.

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正在接受治疗的小儿结核性脑膜炎病例的尿液结核分枝杆菌标记物和菌群失调。

背景：结核性脑膜炎（TBM）的发病机制包括结核分枝杆菌感染脑膜和大脑。然而，最近的研究表明，结核性脑膜炎引发的免疫反应和炎症过程会对肠道微生物群产生重大影响。肠道微生物群的破坏与各种全身性后果有关，包括免疫力改变和代谢失调。TBM引起的炎症、抗生素治疗和宿主免疫力的变化都会影响肠道微生物的组成。TBM 与肠道微生物组之间的这种复杂关系在临床上具有重要意义。为了更深入地了解 TBM 与肠道微生物组之间错综复杂的相互作用，我们报告了对该疾病的发展和治疗反应的创新见解。最终，这将有助于改善TBM患者的治疗效果、管理策略和生活质量：方法：我们采用一种有针对性的液相色谱-串联质谱（LC-MS/MS）方法，通过分析从对照组（n = 40）和确诊为 TBM 的实验组（n = 35）收集的尿样，研究与儿科参与者肠道代谢相关的代谢物，实验组又分为 TBM 第一阶段（n = 8）、第二阶段（n = 11）和第三阶段（n = 16）：我们的代谢组学调查显示，在初步筛选出的 78 种微生物源化合物中，发现了 8 种独特的尿液代谢物：结果：我们的代谢组学调查显示，初步筛选出的 78 种微生物组来源化合物中，有 8 种独特的尿液代谢物被确定为 TBM 中菌群失调的尿液标记物：2-甲基丁酰甘氨酸、3-羟基丙酸、3-甲基巴豆酰甘氨酸、4-羟基硫酸、5-羟基吲哚乙酸、5-羟基己酸、异丁酰甘氨酸和苯乙酰谷氨酰胺：这些结果得到了以往结核病尿液研究的支持，凸显了肠道代谢和确定相应微生物代谢物的重要性，这些代谢物是改善肺结核患者管理的新基础。

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来源期刊

Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY

CiteScore

7.70

自引率

2.40%

发文量

期刊介绍： Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).