Gates Lily, Mistry Talisa, Ogunbiyi Olumide, Kite Kerry-Anne, Klein Nigel J, Sebire Neil J, Alber Dagmar G
Infection, Immunity and Inflammation, UCL GOS Institute of Child Health, London, United Kingdom.
NIHR GOSH Biomedical Research Centre, Histopathology Department, Camelia Botnar Laboratories, Great Ormond Street Hospital, London, United Kingdom.
Front Microbiol. 2023 Jun 15;14:1171670. doi: 10.3389/fmicb.2023.1171670. eCollection 2023.
Sudden unexpected death in infancy (SUDI) is the most common cause of post-neonatal death in the developed world. Following an extensive investigation, the cause of ~40% of deaths remains unknown. It is hypothesized that a proportion of deaths are due to an infection that remains undetected due to limitations in routine techniques. This study aimed to apply 16S rRNA gene sequencing to post-mortem (PM) tissues collected from cases of SUDI, as well as those from the childhood equivalent (collectively known as sudden unexpected death in infancy and childhood or SUDIC), to investigate whether this molecular approach could help identify potential infection-causing bacteria to enhance the diagnosis of infection.
In this study, 16S rRNA gene sequencing was applied to de-identified frozen post-mortem (PM) tissues from the diagnostic archive of Great Ormond Street Hospital. The cases were grouped depending on the cause of death: (i) explained non-infectious, (ii) infectious, and (iii) unknown.
In the cases of known bacterial infection, the likely causative pathogen was identified in 3/5 cases using bacterial culture at PM compared to 5/5 cases using 16S rRNA gene sequencing. Where a bacterial infection was identified at routine investigation, the same organism was identified by 16S rRNA gene sequencing. Using these findings, we defined criteria based on sequencing reads and alpha diversity to identify PM tissues with likely infection. Using these criteria, 4/20 (20%) cases of unexplained SUDIC were identified which may be due to bacterial infection that was previously undetected. This study demonstrates the potential feasibility and effectiveness of 16S rRNA gene sequencing in PM tissue investigation to improve the diagnosis of infection, potentially reducing the number of unexplained deaths and improving the understanding of the mechanisms involved.
婴儿猝死综合征（SUDI）是发达国家新生儿期后死亡的最常见原因。经过广泛调查，约40%的死亡原因仍不明。据推测，一部分死亡是由于常规技术的局限性导致未检测到的感染所致。本研究旨在将16S rRNA基因测序应用于从婴儿猝死综合征病例以及儿童期类似病例（统称为婴儿和儿童期猝死或SUDIC）收集的尸检（PM）组织，以研究这种分子方法是否有助于识别潜在的致病细菌，从而加强感染的诊断。
在本研究中，16S rRNA基因测序应用于大奥蒙德街医院诊断档案中身份不明的冷冻尸检（PM）组织。根据死亡原因对病例进行分组：（i）明确的非感染性，（ii）感染性，以及（iii）不明原因。
在已知细菌感染的病例中，尸检时使用细菌培养在3/5的病例中鉴定出可能的致病病原体，而使用16S rRNA基因测序在5/5的病例中鉴定出致病病原体。在常规调查中鉴定出细菌感染时，16S rRNA基因测序也鉴定出相同的病原体。利用这些发现，我们根据测序读数和α多样性定义了标准，以识别可能存在感染的尸检组织。使用这些标准，在20例不明原因的SUDIC病例中鉴定出4例（20%），可能是由于先前未检测到的细菌感染所致。本研究证明了16S rRNA基因测序在尸检组织调查中用于改善感染诊断的潜在可行性和有效性，可能减少不明原因死亡的数量，并增进对相关机制的理解。
