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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Combined metabolomic and metagenomic analysis reveals inflammatory bowel disease diversity in pediatric and adult patients
Natalya B Zakharzhevskaya, Svetlana I Erdes, Elena A Belousova, Ivan S Samolygo, Marina A Manina, Polina V Kondrashova, Ekaterina Y Lomakina, Dmitry A Kardonsky, Elizaveta A Vorobyeva, Olga Y Shagaleeva, Artemiy A Silantyev, Victoriia D Kazakova, Daria A Kashatnikova, Tatiana N Kalachnuk, Irina V Kolesnikova, Andrey V Chaplin, Maria I Markelova, Tatiana V Grigoryeva, Evgenii I Olekhnovich, Vladimir A Veselovsky, Maxim D Morozov, Polina Y Zoruk, Daria I Boldyreva, Anna A Vanyushkina, Boris A Efimov
Natalya B Zakharzhevskaya, Dmitry A Kardonsky, Elizaveta A Vorobyeva, Olga Y Shagaleeva, Artemiy A Silantyev, Victoriia D Kazakova, Daria A Kashatnikova, Irina V Kolesnikova, Vladimir A Veselovsky, Boris A Efimov, Department of Postgenomics, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
Svetlana I Erdes, Ivan S Samolygo, Marina A Manina, Department of Propaedeutics of Children’s Diseases, N.F. Filatov Clinical Institute of Children’s Health, I.M. Sechenov First Moscow State Medical University, Moscow 119435, Russia
Elena A Belousova, Ekaterina Y Lomakina, Department of Gastroenterology, M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow 129110, Russia
Polina V Kondrashova, Department of Gastroenterology, Children’s City polyclinic No. 81 of the Moscow Department of Health, Moscow 117342, Russia
Daria A Kashatnikova, The Laboratory of Ecological Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119991, Russia
Tatiana N Kalachnuk, Department of Gastroenterology, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
Andrey V Chaplin, Boris A Efimov, Department of Microbiology and Virology, Pirogov Russian National Research Medical University, Moscow 117997, Russia
Maria I Markelova, Tatiana V Grigoryeva, Department of Proteomics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan 420008, Russia
Evgenii I Olekhnovich, Maxim D Morozov, Polina Y Zoruk, Daria I Boldyreva, Department of System Biology, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
Anna A Vanyushkina, Vladimir Zelman Center for Neurobiology and Brain Rehabilitation, Skolkovo Institute of Science and Technology, Moscow 121205, Russia
Author contributions: Zakharzhevskaya NB, Erdes SI, Belousova ES, Lomakina EY, Kardonsky DA, Kalachnuk TN, and Efimov BA contributed to designing experiments; Samolygo IS, Manina MM, Kondrashova PV, Shagaleeva OY, Silantiev AS, Kazakova VD, Kashatnikova DA, Chaplin AV, Veselovsky VA, Morozov DM, Zoruk PY, Boldyreva DI, Vorobyeva EA, Markelova MI, Grigoryeva TV, Kolesnikova IV, Olekhnovich EI, and Vanyushkina AA contributed to performed the experiments; Vorobyeva EA, Markelova MI, Grigoryeva TV, Kolesnikova IV, Olekhnovich EI, and Vanyushkina AA contributed to analyzed the data; Zakharzhevskaya NB, Erdes SI, Belousova ES., Samolygo IS, and Kardonsky DA contributed to wrote the paper; Zakharzhevskaya NB, Belousova ES, and Efimov BA contributed to supervised the project.
Supported by the IBD-ONCO 25-27 Project, No. R&D 125030703327-1.
Institutional review board statement: All experimental procedures were approved by the local ethical committee of Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russian Federation, Russia. Informed consent was obtained from all subjects, No. 1-IBD/ONCO-2.09.2024.
Institutional animal care and use committee statement: The local ethical committee of Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russian Federation, hereby confirms that no animal experiments were conducted as part of the scientific and clinical study titled “Development of a Comprehensive Panel of Diagnostic Markers for Verification of Inflammatory and Oncological Bowel Diseases”, No. 2-IBD/ONCO-2.09.2024.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The genome data supporting the findings of this study are openly available in the NCBI BioProject under accession ID: PRJNA1315228. The metabolome data supporting the findings of this study are openly available in the Mendeley database (Mendeley Data, V1, Available from:
https://data.mendeley.com/datasets/f6vtf4gpcc/1) [DOI: 10.17632/f6vtf4gpcc.1].
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Natalya B Zakharzhevskaya, PhD, Postdoc, Department of Postgenomics, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya, 1A, Moscow 119435, Russia.
natazaha@gmail.com
Received: August 4, 2025
Revised: September 9, 2025
Accepted: November 11, 2025
Published online: December 28, 2025
Processing time: 147 Days and 17.8 Hours
BACKGROUND
The gut microbiota displays pronounced compositional differences between pediatric and adult populations, both under normal conditions and during the development of inflammatory bowel disease (IBD). These structural variations are accompanied by substantial changes in microbial metabolic activity.
AIM
To identify novel early diagnostic biomarkers of IBD, we performed an integrated multi-omics analysis that included assessing microbial community structure and profiling microbial metabolic activity in pediatric and adult cohorts with ulcerative colitis (UC) and Crohn’s disease (CD).
METHODS
The study cohort consisted of two distinct age groups with confirmed IBD diagnoses: Adult patients (aged 45 to 70) and pediatric patients (aged 5 to 15), each diagnosed with either CD or UC. 16S rRNA gene sequencing was performed using the MinION™ Mk1B platform, with data acquisition carried out via MinKNOW software version 22.12.7 (Oxford Nanopore Technologies). Stool samples were analyzed using a Shimadzu QP2010 Ultra GC/MS system equipped with a Shimadzu HS-20 headspace extractor.
RESULTS
Comparative analysis revealed significant age-related differences in the abundance of Bacteroidota, with pediatric IBD patients showing a lower prevalence compared to adults. Microbial profiling identified Streptococcus salivarius and Escherichia coli as potential biomarkers for assessing IBD risk in children. Furthermore, metagenomic analysis uncovered five microbial signatures with diagnostic potential for CD: Ralstonia insidiosa, Stenotrophomonas maltophilia, Erysipelatoclostridium ramosum, Blautia spp., and Coprococcus comes. Using comprehensive metabolomic profiling, we developed and validated novel risk prediction algorithms for pediatric IBD. The CD risk stratification model identifies high-risk patients based on two key biomarkers: An elevated IBD risk coefficient score and reduced levels of 1H-indole-3-methyl. The UC risk prediction model incorporates three metabolic biomarkers indicative of increased disease risk: An elevated risk coefficient score, increased acetate levels, decreased pentanoic acid, and altered excretion of p-cresol (4-methylphenol).
CONCLUSION
Functional metabolomics holds transformative potential for IBD diagnostics across all age groups, with especially significant implications for pediatric patients. The distinct metabolic and metagenetic profiles observed in the pediatric cohort may represent primary alterations in IBD, providing valuable insights for exploring novel mechanisms underlying disease pathogenesis.
Core Tip: Functional metabolomics combines the ability to simultaneously assess the diversity of the microbiome and evaluate its secretory activity in the development of pathologies. In this study, a diagnostic rule was developed for children with inflammatory bowel disease that enables calculation of the risk of disease development. This rule, based on a set of metabolic and metagenomic markers, also helps clarify the specific type of pathology. The combined use of metabolomic and metagenomic analysis will facilitate prompt assessment of the potential risks for developing inflammatory bowel disease in the future and support timely initiation of appropriate therapy.
