Noninvasive Fecal Cytokine and Microbiota 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

Noninvasive Fecal Cytokine and Microbiota Profiles Predict Commencement of Necrotizing Enterocolitis in a Proof-of-Concept Study

Gastro Hep Adv. 2023;2(5):666-675. doi: 10.1016/j.gastha.2023.03.003.

Authors

Christian Zenner¹, Lisa Chalklen², Helena Adjei², Matthew J Dalby², Suparna Mitra^{2

3}, Emma Cornwell⁴, Alexander G Shaw⁴, Kathleen Sim⁴, J Simon Kroll⁴, Lindsay J Hall^{1

2

5}

Affiliations

¹ Intestinal Microbiome, School of Life Sciences, ZIEL - Institute for Food & Health, Technical University of Munich, Freising, Germany.
² Gut Microbes & Health, Quadram Institute Biosciences, Norwich, United Kingdom.
³ Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom.
⁴ Department of Medicine, Section of Paediatric Infectious Disease, Imperial College London, London, United Kingdom.
⁵ Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Abstract

Background and 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 nonspecific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed. We investigated fecal cytokine levels, coupled with gut microbiota profiles, as a noninvasive 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 neonatologists grouped individuals by modified Bell's staging (healthy, NEC1, NEC2/3) and fecal 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 composition were observed for Bacillota (adj. P = .0396), with Enterococcus being the least abundant in Bell stage 2/3 NEC. Evaluation of fecal cytokine levels revealed significantly higher concentrations of IL-1α (P = .045), IL-5 (P = .0074), and IL-10 (P = .032) in Bell stage 1 NEC compared to healthy individuals.

Conclusion: Differences in certain fecal 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.

Abstract

Grants and funding