Gut metabolome and microbiota signatures predict response to treatment with exclusive enteral nutrition in a prospective study in children with active Crohn's disease

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Nichols, Ben, Briola, Anny, Logan, Michael, Havlik, Jaroslav, Mascellani, Anna, Gkikas, Konstantinos, Milling, Simon, Ijaz, Umer Zeeshan, Quince, Christopher, Svolos, Vaios, Russell, Richard K., Hansen, Richard and Gerasimidis, Konstantinos (2024) Gut metabolome and microbiota signatures predict response to treatment with exclusive enteral nutrition in a prospective study in children with active Crohn's disease. American Journal of Clinical Nutrition, 119 (4). pp. 885-895. ISSN 0002-9165

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Abstract

Background: Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization. Objectives: This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD. Methods: In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR). Results: Of 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63–18.4) compared with nonresponders: 22.3 (12.0–32.0); P = 0.03], acetate [responders: 49.9 (46.4–68.4) compared with nonresponders: 70.4 (57.0–95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013–0.611) compared with nonresponders: 0.943 (0.438–1.35); P = 0.021], and a higher microbiota richness [315 (269–347) compared with nonresponders: 243 (205–297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38–0.72) compared with nonresponders: 0.19 (0.01–0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN. Conclusions: We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.

Item Type: Article
Additional Information: Data availability statement: Anonymized data may become available to third parties after request to the corresponding author and for only for those patients who provided written consent for this specific aspect of study participation. Funding Information: This research received funding from The Glasgow Children’s Hospital Charity, Nestle Health Science and The Leona M. and Harry B. Helmsley Charitable Trust. ML received a studentship by the Engineering and Physical Sciences Research Council (EPSRC) and Nestle Health Science. UZI was funded by Natural Environment Research Council (NERC NE/L011956/1) and supported by EPSRC (EP/P029329/1 and EP/V030515/1). BN was partially funded by the Biotechnology and Biological Sciences Research Council (BB/R006539/1).
Uncontrolled Keywords: crohn's disease,cytokines,exclusive enteral nutrition,metabolome,microbiome,o'link,precision therapy,short chain fatty acids,medicine (miscellaneous),nutrition and dietetics ,/dk/atira/pure/subjectarea/asjc/2700/2701
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 24 Oct 2024 14:30
Last Modified: 01 Nov 2024 13:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/97181
DOI: 10.1016/j.ajcnut.2023.12.027

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