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

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.

• Authors: Ben Nichols, Anny Briola, Michael Logan, Jaroslav Havlik, Anna Mascellani, Konstantinos Gkikas, Simon Milling, Umer Zeeshan Ijaz, Christopher Quince, Vaios Svolos, Richard K Russell, Richard Hansen, Konstantinos Gerasimidis
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 119 Issue 4 Pg. 885-895 (Apr 2024) ISSN: 1938-3207 [Electronic] United States
• PMID: 38569785 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Butyrates
• Acetates
• Phenylacetates

Topics

• Child
• Humans
• Crohn Disease (therapy, metabolism)
• Enteral Nutrition
• Prospective Studies
• Remission Induction
• Microbiota
• Metabolome
• Butyrates
• Acetates
• Phenylacetates