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

Christian Zenner; Lisa Chalklen; Helena Adjei; Matthew J. Dalby; Suparna Mitra; Emma Cornwell; Alexander G. Shaw; Kathleen Sim; J. Simon Kroll; Lindsay J. Hall

doi:10.1016/j.gastha.2023.03.003

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

Christian Zenner, Lisa Chalklen, Helena Adjei, Matthew J. Dalby, Suparna Mitra, Emma Cornwell, Alexander G. Shaw, Kathleen Sim, J. Simon Kroll, Lindsay J. Hall

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Abstract

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.

Original language	English
Pages (from-to)	666-675
Number of pages	10
Journal	Gastro Hep Advances
Volume	2
Issue number	5
Early online date	7 Mar 2023
DOIs	https://doi.org/10.1016/j.gastha.2023.03.003
Publication status	Published - 2023

Keywords

Cytokines
Gut Microbiota
Necrotizing Enterocolitis
Noninvasive Biomarkers
Preterm Infants

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@article{25f9021dd73343d29b3de15cdd11f587,

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

abstract = "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{\textquoteright}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{\textquoteright}s or Queen Charlotte{\textquoteright}s & Chelsea) between January 2011 and December 2012. During the NICU stay, expert neonatologist grouped individuals by modified Bell{\textquoteright}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.",

keywords = "Cytokines, Gut Microbiota, Necrotizing Enterocolitis, Noninvasive Biomarkers, Preterm Infants",

author = "Christian Zenner and Lisa Chalklen and Helena Adjei and Dalby, {Matthew J.} and Suparna Mitra and Emma Cornwell and Shaw, {Alexander G.} and Kathleen Sim and Kroll, {J. Simon} and Hall, {Lindsay J.}",

note = "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.",

year = "2023",

doi = "10.1016/j.gastha.2023.03.003",

language = "English",

volume = "2",

pages = "666--675",

journal = "Gastro Hep Advances",

issn = "2772-5723",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - Non-invasive faecal cytokine and microbiome profiles predict commencement of necrotizing enterocolitis in a proof-of-concept study

AU - Zenner, Christian

AU - Chalklen, Lisa

AU - Adjei, Helena

AU - Dalby, Matthew J.

AU - Mitra, Suparna

AU - Cornwell, Emma

AU - Shaw, Alexander G.

AU - Sim, Kathleen

AU - Kroll, J. Simon

AU - Hall, Lindsay J.

N1 - 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.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Cytokines

KW - Gut Microbiota

KW - Necrotizing Enterocolitis

KW - Noninvasive Biomarkers

KW - Preterm Infants

UR - http://www.scopus.com/inward/record.url?scp=85173968645&partnerID=8YFLogxK

U2 - 10.1016/j.gastha.2023.03.003

DO - 10.1016/j.gastha.2023.03.003

M3 - Article

SN - 2772-5723

VL - 2

SP - 666

EP - 675

JO - Gastro Hep Advances

JF - Gastro Hep Advances

IS - 5

ER -

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

Abstract

Keywords

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