Non-invasive faecal cytokine and microbiome profiles predict commencement of necrotizing enterocolitis in a proof-of-concept study

Zenner, Christian, Chalklen, Lisa, Adjei, Helena, Dalby, Matthew J., Mitra, Suparna, Cornwell, Emma, Shaw, Alexander G., Sim, Kathleen, Kroll, J. Simon and Hall, Lindsay J. ORCID: (2023) Non-invasive faecal cytokine and microbiome profiles predict commencement of necrotizing enterocolitis in a proof-of-concept study. Gastro Hep Advances, 2 (5). pp. 666-675. ISSN 2772-5723

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Background & Aims: Necrotizing enterocolitis (NEC) is a life-threatening disease, and the most common gastrointestinal emergency in premature infants. Accurate early diagnosis is challenging. Modified Bell’s staging is routinely used to guide diagnosis, but early diagnostic signs are non-specific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed. We investigated faecal cytokine levels, coupled with gut microbiota profiles, as a non-invasive method to discover specific NEC-associated signatures that can be applied as potential diagnostic markers.   Methods: Premature babies born below 32 weeks of gestation were admitted to the 2-site neonatal intensive care unit (NICU) of Imperial College hospitals (St. Mary’s or Queen Charlotte’s & Chelsea) between January 2011 and December 2012. During the NICU stay, expert neonatologist grouped individuals by modified Bell’s staging (healthy, NEC1, NEC2/3) and faecal samples from diapers were collected consecutively. Microbiota profiles were assessed by 16S rRNA gene amplicon sequencing and cytokine concentrations were measured by V-Plex multiplex assays.   Results: Early evaluation of microbiota profiles revealed only minor differences. However, at later time points, significant changes in microbiota structure were observed for Bacillota (adj. p=0.0396), with Enterococcus being the least abundant in Bell stage 2/3 NEC. Evaluation of faecal cytokine levels revealed significantly higher concentrations of IL-1α (p=0.045), IL-5 (p=0.0074), and IL-10 (p=0.032) in Bell stage 1 NEC compared to healthy individuals.   Conclusions: Differences in certain faecal cytokine profiles in patients with NEC indicate their potential use as diagnostic biomarkers to facilitate earlier diagnosis. Additionally, associations between microbial and cytokine profiles contribute to improving knowledge about NEC pathogenesis.

Item Type: Article
Additional Information: Funding Information: Prof Hall is supported by Wellcome Trust Investigator Awards (100974/C/13/Z and 220876/Z/20/Z); the Biotechnology and Biological Sciences Research Council (BBSRC), Institute Strategic Programme Gut Microbes and Health (BB/R012490/1), and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356. Work at Imperial College was supported by a programme grant from the Winnicott Foundation to JSK, and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial Healthcare NHS Trust and Imperial College London. Dr Sim was funded by an NIHR Doctoral Research Fellowship [NIHR- DRF-2011-04-128 ]. All other authors received no external funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Uncontrolled Keywords: cytokines,gut microbiota,necrotizing enterocolitis,noninvasive biomarkers,preterm infants,medicine (miscellaneous),gastroenterology,hepatology ,/dk/atira/pure/subjectarea/asjc/2700/2701
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 07 Mar 2023 17:30
Last Modified: 26 Oct 2023 02:17
DOI: 10.1016/j.gastha.2023.03.003


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