Targeted <sup>1</sup>H NMR metabolomics and immunological phenotyping of human fresh blood and serum samples discriminate between healthy individuals and inflammatory bowel disease patients treated with anti-TNF

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Abstract

Inflammatory bowel disease is a multifactorial etiology, associated with environmental factors that can trigger both debut and relapses. A high level of tumor necrosis factor-α in the gut is the main consequence of immune system imbalance. The aim of treatment is to restore gut homeostasis. In this study, fresh blood and serum samples were used to identify biomarkers and to discriminate between Crohn’s disease and ulcerative colitis patients under remission treated with anti-TNF. Metabolomics based on Nuclear Magnetic Resonance spectroscopy (NMR) was used to detect unique biomarkers for each class of patients. Blood T lymphocyte repertories were characterized, as well as cytokine and transcription factor profiling, to complement the metabolomics data. Higher levels of homoserine-methionine and isobutyrate were identified as biomarkers of Crohn’s disease with ileocolic localization. For ulcerative colitis, lower levels of creatine-creatinine, proline, and tryptophan were found that reflect a deficit in the absorption of essential amino acids in the gut. T lymphocyte phenotyping and its functional profiling revealed that the overall inflammation was lower in Crohn’s disease patients than in those with ulcerative colitis. These results demonstrated that NMR metabolomics could be introduced as a high-throughput evaluation method in routine clinical practice to stratify both types of patients related to their pathology.

Key messages

NMR metabolomics is a non-invasive tool that could be implemented in the normal clinical practice for IBD to assess beneficial effect of the treatment.
NMR metabolomics is a useful tool for precision medicine, in order to sew a specific treatment to a specific group of patients.
Finding predictors of response to IFX would be desirable to select patients affected by IBD.
Immunological status of inflammations correlates with NMR metabolomics biomarkers.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00109-021-02094-y.

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Metabolic profiling, metabolomic and metabonomic studies mainly involve the multicomponent analysis of biological fluids, tissue and cell extracts using NMR spectroscopy and/or mass spectrometry (MS). We summarize the main NMR spectroscopic applications in modern metabolic research, and provide detailed protocols for biofluid (urine, serum/plasma) and tissue sample collection and preparation, including the extraction of polar and lipophilic metabolites from tissues. 1H NMR spectroscopic techniques such as standard 1D spectroscopy, relaxation-edited, diffusion-edited and 2D J-resolved pulse sequences are widely used at the analysis stage to monitor different groups of metabolites and are described here. They are often followed by more detailed statistical analysis or additional 2D NMR analysis for biomarker discovery. The standard acquisition time per sample is 4-5 min for a simple 1D spectrum, and both preparation and analysis can be automated to allow application to high-throughput screening for clinical diagnostic and toxicological studies, as well as molecular phenotyping and functional genomics.

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Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

Lan Lin, Jianqiong Zhang (2017)

Background A vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health. Methods This paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA). Results In addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction. Conclusions A better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment.

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Author and article information

Contributors

Sara Notararigo:

ORCID: http://orcid.org/0000-0001-9841-5500

sarita.not@hotmail.com

Journal

Journal ID (nlm-ta): J Mol Med (Berl)

Journal ID (iso-abbrev): J Mol Med (Berl)

Title: Journal of Molecular Medicine (Berlin, Germany)

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0946-2716

ISSN (Electronic): 1432-1440

Publication date (Electronic): 21 May 2021

Publication date PMC-release: 21 May 2021

Publication date (Print): 2021

Volume: 99

Issue: 9

Pages: 1251-1264

Affiliations

[1 ]GRID grid.411048.8, ISNI 0000 0000 8816 6945, Instituto de Investigación Sanitaria de Santiago (IDIS), , Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), ; 15706 Santiago de Compostela, A Coruña Spain

[2 ]GRID grid.11794.3a, ISNI 0000000109410645, Unidade de Resonancia Magnética, Área de Infraestruturas de Investigación, CACTUS, , University Santiago de Compostela, ; 15782 Santiago de Compostela, A Coruña Spain

Author information

Sara Notararigo http://orcid.org/0000-0001-9841-5500

Article

Publisher ID: 2094

DOI: 10.1007/s00109-021-02094-y

PMC ID: 8367886

PubMed ID: 34021361

SO-VID: e980621f-3cc2-498f-9546-2b5a4cc34aae

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 30 October 2020

Date revision received : 19 April 2021

Date accepted : 13 May 2021

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: nmr metabolomics,ibd stratification,ibd metabolomic profiling

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ScienceOpen disciplines: Molecular medicine

Keywords: nmr metabolomics, ibd stratification, ibd metabolomic profiling

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