Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Sensors (Basel). 2024 May 16;24(10):3162. doi: 10.3390/s24103162.
Early diagnosis and treatment of late-onset sepsis (LOS) is crucial for survival, but challenging. Intestinal microbiota and metabolome alterations precede the clinical onset of LOS, and the preterm gut is considered an important source of bacterial pathogens. Fecal volatile organic compounds (VOCs), formed by physiologic and pathophysiologic metabolic processes in the preterm gut, reflect a complex interplay between the human host, the environment, and microbiota. Disease-associated fecal VOCs can be detected with an array of devices with various potential for the development of a point-of-care test (POCT) for preclinical LOS detection. While characteristic VOCs for common LOS pathogens have been described, their VOC profiles often overlap with other pathogens due to similarities in metabolic pathways, hampering the construction of species-specific profiles. Clinical studies have, however, successfully discriminated LOS patients from healthy individuals using fecal VOC analysis with the highest predictive value for Gram-negative pathogens. This review discusses the current advancements in the development of a non-invasive fecal VOC-based POCT for early diagnosis of LOS, which may potentially provide opportunities for early intervention and targeted treatment and could improve clinical neonatal outcomes. Identification of confounding variables impacting VOC synthesis, selection of an optimal detection device, and development of standardized sampling protocols will allow for the development of a novel POCT in the near future.
早期诊断和治疗晚发性败血症（LOS）对生存至关重要，但具有挑战性。肠道微生物群和代谢组的改变先于 LOS 的临床发作，早产儿的肠道被认为是细菌病原体的重要来源。粪便挥发性有机化合物（VOCs）是由早产儿肠道的生理和病理代谢过程形成的，反映了人类宿主、环境和微生物群之间的复杂相互作用。一系列设备可以检测到与疾病相关的粪便 VOCs，这些设备具有开发用于临床前 LOS 检测的即时检测（POCT）的各种潜力。虽然已经描述了常见 LOS 病原体的特征性 VOCs，但由于代谢途径的相似性，它们的 VOC 谱经常与其他病原体重叠，从而阻碍了特定物种的谱的构建。然而，临床研究已经成功地使用粪便 VOC 分析将 LOS 患者与健康个体区分开来，这种方法对革兰氏阴性病原体具有最高的预测价值。这篇综述讨论了开发基于非侵入性粪便 VOC 的 LOS 早期诊断的 POCT 的最新进展，这可能为早期干预和靶向治疗提供机会，并改善临床新生儿结局。确定影响 VOC 合成的混杂变量、选择最佳检测设备以及开发标准化采样方案将有助于在不久的将来开发一种新的 POCT。
