Nichols, B. et al. (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. (doi: 10.1016/j.ajcnut.2023.12.027) (PMID:38569785) (PMCID:PMC11007740)
Text
315817_Suppl_Tables.pdf - Supplemental Material 235kB | |
Text
315817_Suppl_Figures.pdf - Supplemental Material 655kB | |
Text
315817_Suppl_Methods.pdf - Supplemental Material 152kB | |
Text
315817.pdf - Published Version Available under License Creative Commons Attribution. 508kB |
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: | Articles |
---|---|
Additional 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). |
Keywords: | Exclusive enteral nutrition, Crohn’s disease, microbiome, precision therapy, metabolome, short chain fatty acids, o'link, cytokines. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Hansen, Dr Richard and Russell, Dr Richard and Logan, Dr Michael and Havlik, Dr Jaroslav and Svolos, Dr Vaios and Gkikas, Dr Konstantinos and Nichols, Mr Ben and Milling, Professor Simon and Quince, Dr Christopher and Gerasimidis, Professor Konstantinos and BRIOLA, Ms ANNA and Ijaz, Dr Umer |
Authors: | Nichols, B., Briola, A., Logan, M., Havlik, J., Mascellani, A., Gkikas, K., Milling, S., Ijaz, U. Z., Quince, C., Svolos, V., Russell, R. K., Hansen, R., and Gerasimidis, K. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing College of Science and Engineering > School of Engineering College of Science and Engineering > School of Engineering > Infrastructure and Environment |
Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
Journal Name: | American Journal of Clinical Nutrition |
Publisher: | Elsevier |
ISSN: | 0002-9165 |
ISSN (Online): | 1938-3207 |
Published Online: | 19 February 2024 |
Copyright Holders: | Copyright © 2024 The Authors |
First Published: | First published in American Journal of Clinical Nutrition 119(4):885-895 |
Publisher Policy: | Reproduced under a Creative Commons License |
University Staff: Request a correction | Enlighten Editors: Update this record