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For: Martin FP, Su MM, Xie GX, Guiraud SP, Kussmann M, Godin JP, Jia W, Nydegger A. Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children. World J Gastroenterol 2017; 23(20): 3643-3654 [PMID: 28611517 DOI: 10.3748/wjg.v23.i20.3643] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] Open

For:	Martin FP, Su MM, Xie GX, Guiraud SP, Kussmann M, Godin JP, Jia W, Nydegger A. Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children. World J Gastroenterol 2017; 23(20): 3643-3654 [PMID: 28611517 DOI: 10.3748/wjg.v23.i20.3643] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] Open

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Cited by Other Article(s)

DeSantis AH, Buss K, Coker KM, Pasternak BA, Chi J, Patterson JS, Gu H, Jurutka PW, Sandrin TR. Multiomics-Based Profiling of the Fecal Microbiome Reveals Potential Disease-Specific Signatures in Pediatric IBD (PIBD). Biomolecules 2025;15:746. [PMID: 40427639 DOI: 10.3390/biom15050746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 05/16/2025] [Accepted: 05/17/2025] [Indexed: 05/29/2025] Open

Abstract

Inflammatory bowel disease (IBD), which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), is a chronic gastrointestinal (GI) disorder affecting 1 in 100 people in the United States. Pediatric IBD (PIBD) is estimated to impact 15 per 100,000 children in North America. Factors such as the gut microbiome (GM), genetic predisposition to the disease, and certain environmental factors are thought to be involved in pathogenesis. However, the pathophysiology of IBD is incompletely understood, and diagnostic biomarkers and effective treatments, particularly for PIBD, are limited. Recent work suggests that these factors may interact to influence disease development, and multiomic approaches have emerged as promising tools to elucidate the pathophysiology. We employed metagenomics, metabolomics- and metatranscriptomics-based approaches to examine the microbiome, its genetic potential, and its activity to identify factors associated with PIBD. Metagenomics-based analyses revealed pathways such as octane oxidation and glycolysis that were differentially expressed in UC patients. Additionally, metatranscriptomics-based analyses suggested enrichment of glycan degradation and two component systems in UC samples as well as protein processing in the endoplasmic reticulum, ribosome, and protein export in CD and UC samples. In addition, metabolomics-based approaches revealed patterns of differentially abundant metabolites between healthy and PIBD individuals. Interestingly, overall microbiome community composition (as measured by alpha and beta diversity indices) did not appear to be associated with PIBD. However, we observed a small number of differentially abundant taxa in UC versus healthy controls, including members of the Classes Gammaproteobacteria and Clostridia as well as members of the Family Rikenellaceae. Accordingly, when identifying potential biomarkers for PIBD, our results suggest that multiomics-based approaches afford enhanced potential to detect putative biomarkers for PIBD compared to microbiome community composition sequence data alone.

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Baskaran K, Moshkovich M, Hart L, Shah N, Chowdhury F, Shanmuganathan M, Britz-McKibbin P, Pai N. The role of urine metabolomics in the diagnosis and management of adult and pediatric Crohn's disease and ulcerative colitis. Biomarkers 2025;30:104-113. [PMID: 39642943 DOI: 10.1080/1354750x.2024.2438734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 12/02/2024] [Indexed: 12/09/2024]

Abstract

INTRODUCTION

Urine metabolomics offers a non-invasive approach to diagnose and manage inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), by identifying distinct metabolic signatures.

OBJECTIVES

This narrative review summarizes current findings on urinary metabolites in IBD, evaluating their roles in disease differentiation, assessment of activity, and monitoring therapeutic response.

METHODS

A comprehensive literature search of PubMed and MEDLINE up to October 2023 was conducted using keywords, such as 'urine metabolomics', 'inflammatory bowel disease', 'Crohn's disease', 'ulcerative colitis', and 'urinary biomarkers'. Studies were included that described alterations to metabolic pathways, including those related to the urea cycle, central energy metabolism (Krebs cycle), amino acid metabolism, and neurotransmitters.

RESULTS

Specific urinary metabolites differentiate IBD patients from healthy controls and between CD and UC. Decreased urinary levels of hippurate, acetate, methanol, formate, and methylamine are observed in IBD, indicating altered gut microbiota. In CD patients, urea cycle alterations include reduced urinary urea and ornithine with increased arginine. Changes in Krebs cycle intermediates show decreased citrate and succinate in adults, but increased fumarate and isocitrate in pediatric patients, reflecting energy metabolism differences. Amino acid metabolism differs by age: Adults exhibit decreased urinary asparagine, lysine, and histidine, while pediatric patients show increased methionine, proline, aspartic acid, and isoleucine. Elevated urinary neurotransmitters like dopamine are noted in pediatric IBD patients. Urine metabolomics also can monitor treatment efficacy by distinguishing responders from non-responders to therapies and differentiating active disease from remission.

CONCLUSION

Urine metabolomics provides promising, non-invasive biomarkers to enhance IBD diagnostics by distinguishing CD from UC and offering insights into underlying metabolic disturbances, paving the way for more precise, accessible patient care.

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Ma Y, Yang H, Wang X, Huang Y, Li Y, Pan G. Bile acids as signaling molecules in inflammatory bowel disease: Implications for treatment strategies. JOURNAL OF ETHNOPHARMACOLOGY 2025;337:118968. [PMID: 39427739 DOI: 10.1016/j.jep.2024.118968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 09/21/2024] [Accepted: 10/17/2024] [Indexed: 10/22/2024]

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Inflammatory bowel disease (IBD) is a globally increasing disease. Despite continuous efforts, the clinical application of treatment drugs has not achieved satisfactory success and faces limitations such as adverse drug reactions. Numerous investigations have found that the pathogenesis of IBD is connected with disturbances in bile acid circulation and metabolism. Traditional Chinese medicine targeting bile acids (BAs) has shown significant therapeutic effects and advantages in treating inflammatory bowel disease.

AIM OF THIS REVIEW

IThis article reviews the role of bile acids and their receptors in IBD, as well as research progress on IBD therapeutic drugs based on bile acids. It explores bile acid metabolism and its interaction with the intestinal microbiota, summarizes clinical drugs for treating IBD including single herbal medicine, traditional herbal prescriptions, and analyzes the mechanisms of action in treating IBD.

MATERIALS AND METHODS

IThe electronic databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) have been utilized to retrieve relevant literature up to January 2024, using keywords "bile acid", "bile acid receptor", "inflammatory bowel disease", "intestinal microbiota" and "targeted drugs".

RESULTS

IImbalance in bile acid levels can lead to intestinal inflammation, while IBD can disrupt the balance of microbes, result in alterations in the bile acid pool's composition and amount. This change can damage of intestinal mucosa healing ability. Bile acids are vital for keeping the gut barrier function intact, regulating gene expression, managing metabolic equilibrium, and influencing the properties and roles of the gut's microbial community. Consequently, focusing on bile acids could offer a potential treatment strategy for IBD.

CONCLUSION

IIBD can induce intestinal homeostasis imbalance and changes in BA pool, leading to fluctuations in levels of relevant metabolic enzymes, transporters, and nuclear receptors. Therefore, by regulating the balance of BA and key signaling molecules of bile acids, we can treat IBD. Traditional Chinese medicine has great potential and promising prospects in treating IBD. We should focus on the characteristics and advantages of Chinese medicine, promote the development and clinical application of innovative Chinese medicine, and ultimately make Chinese medicine targeting bile acids the mainstream treatment for IBD.

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Tsoukalas D, Sarandi E, Fragoulakis V, Xenidis S, Mhliopoulou M, Charta M, Paramera E, Papakonstantinou E, Tsatsakis A. Metabolomics-based treatment for chronic diseases: results from a multidisciplinary clinical study. BMJ Nutr Prev Health 2024;7:e000883. [PMID: 39882279 PMCID: PMC11773651 DOI: 10.1136/bmjnph-2024-000883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 11/20/2024] [Indexed: 01/31/2025] Open

Abstract

Background

Non-communicable diseases (NCDs), known as chronic diseases, significantly impact patients' quality of life (QoL) and increase medical expenses. The majority of risk factors are modifiable, and metabolomics has been suggested as a promising strategy for their evaluation, though real-world data are scarce. This study evaluated the QoL improvement and cost-effectiveness of a metabolomics-based treatment for NCDs, aiming to restore metabolic dysfunctions and nutritional deficiencies.

Methods

We performed a pre-post intervention analysis using clinical, metabolomics, QoL and economic data obtained from the electronic health records of 765 patients visiting a private practice. The intervention consisted of personalised treatment to restore metabolic dysfunctions and nutritional deficiencies identified by metabolomics alongside the standard treatment for their condition. The mean intervention duration was 401 days.

Results

Significant improvement was identified in energy levels, sleep quality, gastrointestinal function and physical activity (p<0.001). 67.9% of participants reported significant improvement in the overall QoL, and the average quality-adjusted life-years (QALYs) increased by 0.064 (95% uncertainty interval 0.050 to 0.078) post-treatment. The incremental cost-effectiveness ratio was estimated at €49.774/QALY (95% CI €40.110 to €61.433). Metabolic profiling demonstrated that 16/35 organic acids and 11/24 total fatty acids were significantly changed post-treatment (p<0.001), participating in key pathways such as energy metabolism, microbiome and neurotransmitter turnover. Vitamin D and 5-methyltetrahydrofolate insufficiency was significantly restored (p=0.036).

Conclusion

This is the first study providing evidence that the integration of metabolomics in clinical practice can have a clinical benefit for patients' QoL and may be a cost-effective method.

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Kim S, Thapa I, Ali H. A novel computational approach for the mining of signature pathways using species co-occurrence networks in gut microbiomes. BMC Microbiol 2024;24:490. [PMID: 39574009 PMCID: PMC11580338 DOI: 10.1186/s12866-024-03633-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 11/05/2024] [Indexed: 11/25/2024] Open

Jia D, Tian X, Chen Y, Liu J, Wang M, Hao Z, Wang C, Zhao D. Preparation of enzymatic hydrolysates of mulberry leaf flavonoids and investigation into its treatment and mechanism for zebrafish inflammatory bowel disease. FISH & SHELLFISH IMMUNOLOGY 2024;154:109960. [PMID: 39393613 DOI: 10.1016/j.fsi.2024.109960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/24/2024] [Accepted: 10/09/2024] [Indexed: 10/13/2024]

Abstract

INTRODUCTION

The incidence of inflammatory bowel disease (IBD) has been increasing year by year in recent years. Flavonoids are the main components of mulberry leaves exerting anti-inflammatory effects and have potential applications in drug screening for IBD treatment. Enzymatic hydrolysis can enhance the bioavailability and activity of flavonoid glycosides. No relevant reports on the potentiation of mulberry leaf flavonoids (MLF) after deglycosylation have been retrieved.

METHODS

An enzymatic method was used to prepare enzymatic hydrolysates of MLF (EMLF). The protective effect of EMLF on zebrafish with IBD was evaluated by observing zebrafish intestinal length and width, intestinal histopathological morphology, as well as neutrophil and goblet expression. Network pharmacology and metabolomics were performed to explore the mechanism of action of EMLF against IBD. Finally, the mechanism of EMLF against IBD was validated using Western Blot and real-time quantitative polymerase chain reaction (RT-qPCR).

RESULTS

The EMLF was successfully prepared by hydrolyzing MLF with snailase for the first time, and the anti-inflammatory effect of EMLF was clarified to be superior to that of MLF in IBD zebrafish. The network pharmacology and metabolomics studies showed that the mechanism of EMLF for IBD may be related to regulation of purine metabolic pathway. The expression levels of adenosine deaminase (ADA), critical targets in purine metabolism, were significantly down-regulated, while the expression of adenine phosphoribosyltransferase (APRT) and xanthine dehydrogenase (XDH) was significantly increased when compared with the TNBS group.

CONCLUSION

The results suggested that enzymatic deglycosylation is an effective measure to enhance the anti-inflammatory activity of MLF, which provides referable ideas and methods for the deep processing and utilization of natural drug resources.

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Xiang B, Zhang Q, Wu H, Lin J, Xu Z, Zhang M, Zhu L, Hu J, Zhi M. Impact of Mild COVID-19 History on Oral-Gut Microbiota and Serum Metabolomics in Adult Patients with Crohn's Disease: Potential Beneficial Effects. Biomedicines 2024;12:2103. [PMID: 39335616 PMCID: PMC11429124 DOI: 10.3390/biomedicines12092103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/01/2024] [Accepted: 09/08/2024] [Indexed: 09/30/2024] Open

Affiliation(s)

Bingjie Xiang Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; (B.X.); (Q.Z.); (H.W.); (J.L.); (Z.X.); (M.Z.) Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China
Qi Zhang Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; (B.X.); (Q.Z.); (H.W.); (J.L.); (Z.X.); (M.Z.) Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China
Huibo Wu Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; (B.X.); (Q.Z.); (H.W.); (J.L.); (Z.X.); (M.Z.) Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China
Jue Lin Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; (B.X.); (Q.Z.); (H.W.); (J.L.); (Z.X.); (M.Z.) Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China
Zhaoyuan Xu Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; (B.X.); (Q.Z.); (H.W.); (J.L.); (Z.X.); (M.Z.) Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China
Min Zhang Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; (B.X.); (Q.Z.); (H.W.); (J.L.); (Z.X.); (M.Z.) Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China
Lixin Zhu Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
Jun Hu Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
Min Zhi Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; (B.X.); (Q.Z.); (H.W.); (J.L.); (Z.X.); (M.Z.) Guangdong Institute of Gastroenterology, Guangzhou 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510655, China Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China

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Chen SJ, Zhang DY, Wu X, Zhang FM, Cui BT, Huang YH, Zhang ZL, Wang R, Bai FH. Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study. World J Gastroenterol 2024;30:1572-1587. [PMID: 38617453 PMCID: PMC11008410 DOI: 10.3748/wjg.v30.i11.1572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 02/07/2024] [Accepted: 03/06/2024] [Indexed: 03/21/2024] Open

Abstract

BACKGROUND

Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported.

AIM

To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.

METHODS

We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure.

RESULTS

Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT.

CONCLUSION

WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

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Aldars-García L, Gil-Redondo R, Embade N, Riestra S, Rivero M, Gutiérrez A, Rodríguez-Lago I, Fernández-Salazar L, Ceballos D, Manuel Benítez J, Aguas M, Baston-Rey I, Bermejo F, José Casanova M, Lorente R, Ber Y, Ginard D, Esteve M, de Francisco R, García MJ, Francés R, Rodríguez Pescador A, Velayos B, Del Río EG, Marín Pedrosa S, Minguez Sabater A, Barreiro-de Acosta M, Algaba A, Verdejo Gil C, Rivas O, Royo V, Aceituno M, Garre A, Baldán-Martín M, Ramírez C, Sanz-García A, Lozano JJ, Sidorova J, Millet O, Bernardo D, Gisbert JP, Chaparro M. Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients. Inflamm Bowel Dis 2024;30:167-182. [PMID: 37536268 DOI: 10.1093/ibd/izad154] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Indexed: 08/05/2023]

Abstract

BACKGROUND AND AIMS

Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation.

METHODS

Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses.

RESULTS

A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters.

CONCLUSIONS

This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

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Affiliation(s)

Laila Aldars-García Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
Rubén Gil-Redondo Precision Medicine and Metabolism Lab, CIC bioGUNE, Derio, Spain
Nieves Embade Precision Medicine and Metabolism Lab, CIC bioGUNE, Derio, Spain
Sabino Riestra Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
Montserrat Rivero Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Marqués de Valdecilla, Santander, Spain
Ana Gutiérrez Hospital General Universitario de Alicante, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
Iago Rodríguez-Lago Hospital Universitario de Galdakao, Biocruces Bizkaia Health Research Institute, Vizcaya, Spain
Luis Fernández-Salazar Hospital Clínico Universitario de Valladolid, Valladolid, Spain
Daniel Ceballos Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
José Manuel Benítez Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain
Mariam Aguas Hospital Universitari i Politecnic La Fe, La Fe Health Research Institute, Valencia, Spain
Iria Baston-Rey Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain
Fernando Bermejo Hospital Universitario de Fuenlabrada, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain
María José Casanova Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
Rufo Lorente Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
Yolanda Ber Hospital San Jorge, Huesca, Spain
Daniel Ginard Hospital Universitari Son Espases, Palma de Mallorca, Spain
María Esteve Hospital Universitari Mutua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Terrassa, Spain
Ruth de Francisco Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
María José García Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Marqués de Valdecilla, Santander, Spain
Rubén Francés Hospital Clínico Universitario de Valladolid, Valladolid, Spain
Ainhoa Rodríguez Pescador Hospital Universitario de Galdakao, Biocruces Bizkaia Health Research Institute, Vizcaya, Spain
Benito Velayos Hospital Clínico Universitario de Valladolid, Valladolid, Spain
Elena Guerra Del Río Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
Sandra Marín Pedrosa Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain
Alejandro Minguez Sabater Hospital Universitari i Politecnic La Fe, La Fe Health Research Institute, Valencia, Spain
Manuel Barreiro-de Acosta Departamento Medicina Clínica, Universidad Miguel Hernández de Elche, Instituto Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Universidad Miguel Herñandez, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Investigación Sanitaria y Biomédica de Alicante, Elche, Spain
Alicia Algaba Hospital Universitario de Galdakao, Biocruces Bizkaia Health Research Institute, Vizcaya, Spain
Cristina Verdejo Gil Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
Olga Rivas Hospital San Jorge, Huesca, Spain
Vanesa Royo Hospital Universitari Son Espases, Palma de Mallorca, Spain
Montserrat Aceituno Hospital Universitari Mutua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Terrassa, Spain
Ana Garre Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
Montserrat Baldán-Martín Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
Cristina Ramírez Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
Ancor Sanz-García Data Analysis Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spain
Juan J Lozano Bioinformatics Platform, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
Julia Sidorova Bioinformatics Platform, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
Oscar Millet Precision Medicine and Metabolism Lab, CIC bioGUNE, Derio, Spain
David Bernardo Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biología y Genética Molecular, Universidad de Valladolid, Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Madrid, Spain
Javier P Gisbert Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
María Chaparro Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain

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Paul KC, Zhang K, Walker DI, Sinsheimer J, Yu Y, Kusters C, Del Rosario I, Folle AD, Keener AM, Bronstein J, Jones DP, Ritz B. Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson's disease. Mol Neurodegener 2023;18:100. [PMID: 38115046 PMCID: PMC10731845 DOI: 10.1186/s13024-023-00694-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 12/06/2023] [Indexed: 12/21/2023] Open

Abstract

BACKGROUND

Untargeted high-resolution metabolomic profiling provides simultaneous measurement of thousands of metabolites. Metabolic networks based on these data can help uncover disease-related perturbations across interconnected pathways.

OBJECTIVE

Identify metabolic disturbances associated with Parkinson's disease (PD) in two population-based studies using untargeted metabolomics.

METHODS

We performed a metabolome-wide association study (MWAS) of PD using serum-based untargeted metabolomics data derived from liquid chromatography with high-resolution mass spectrometry (LC-HRMS) using two distinct population-based case-control populations. We also combined our results with a previous publication of 34 metabolites linked to PD in a large-scale, untargeted MWAS to assess external validation.

RESULTS

LC-HRMS detected 4,762 metabolites for analysis (HILIC: 2716 metabolites; C18: 2046 metabolites). We identified 296 features associated with PD at FDR<0.05, 134 having a log2 fold change (FC) beyond ±0.5 (228 beyond ±0.25). Of these, 104 were independently associated with PD in both discovery and replication studies at p<0.05 (170 at p<0.10), while 27 were associated with levodopa-equivalent dose among the PD patients. Intriguingly, among the externally validated features were the microbial-related metabolites, p-cresol glucuronide (FC=2.52, 95% CI=1.67, 3.81, FDR=7.8e-04) and p-cresol sulfate. P-cresol glucuronide was also associated with motor symptoms among patients. Additional externally validated metabolites associated with PD include phenylacetyl-L-glutamine, trigonelline, kynurenine, biliverdin, and pantothenic acid. Novel associations include the anti-inflammatory metabolite itaconate (FC=0.79, 95% CI=0.73, 0.86; FDR=2.17E-06) and cysteine-S-sulfate (FC=1.56, 95% CI=1.39, 1.75; FDR=3.43E-11). Seventeen pathways were enriched, including several related to amino acid and lipid metabolism.

CONCLUSIONS

Our results revealed PD-associated metabolites, confirming several previous observations, including for p-cresol glucuronide, and newly implicating interesting metabolites, such as itaconate. Our data also suggests metabolic disturbances in amino acid and lipid metabolism and inflammatory processes in PD.

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Wu R, Xiong R, Li Y, Chen J, Yan R. Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation. J Autoimmun 2023;141:103062. [PMID: 37246133 DOI: 10.1016/j.jaut.2023.103062] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 05/30/2023]

Abstract

Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.

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Kragsnaes MS, Miguens Blanco J, Mullish BH, Serrano‐Contreras JI, Kjeldsen J, Horn HC, Pedersen JK, Munk HL, Nilsson AC, Salam A, Lewis MR, Chekmeneva E, Kristiansen K, Marchesi JR, Ellingsen T. Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial. ACR Open Rheumatol 2023;5:583-593. [PMID: 37736702 PMCID: PMC10642255 DOI: 10.1002/acr2.11604] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 08/17/2023] [Accepted: 08/22/2023] [Indexed: 09/23/2023] Open

Abstract

OBJECTIVE

We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).

METHODS

This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1 H Nuclear Magnetic Resonance.

RESULTS

Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).

CONCLUSION

Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

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Ma R, Zhu Y, Li X, Hu S, Zheng D, Xiong S, Xu S, Xiang L, Zhao M, Tang C, Zeng Z, Chen M, Feng R. A Novel Serum Metabolomic Panel for the Diagnosis of Crohn's Disease. Inflamm Bowel Dis 2023;29:1524-1535. [PMID: 37195904 DOI: 10.1093/ibd/izad080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Indexed: 05/19/2023]

Abstract

BACKGROUND

A distinctive metabolic phenotype provides the opportunity to discover noninvasive biomarkers for the diagnosis of Crohn's disease (CD) and for differentiating it from other intestinal inflammatory diseases. The study sought to identify new biomarkers for CD diagnosis.

METHODS

Serum metabolites from 68 newly diagnosed and treatment-naïve patients with CD and 56 healthy control (HC) subjects were profiled using targeted liquid chromatography-mass spectrometry. Five metabolic biomarkers were identified to distinguish patients with CD from the HC subjects and validated in a separate cohort consisting of 110 patients with CD and 90 HC subjects using a combination of univariate analysis, orthogonal partial least-squares discriminant analysis, and receiver-operating characteristic curve analysis. Differences in the 5 metabolites were evaluated among patients with CD and patients with ulcerative colitis (n = 62), intestinal tuberculosis (n = 48), and Behçet's disease (n = 31).

RESULTS

Among the 185 quantified metabolites, a panel of 5 (pyruvate, phenylacetylglutamine, isolithocholic acid, taurodeoxycholic acid, and glycolithocholic acid) were found to distinguish patients with CD with high accuracy from HC subjects, with an area under the curve of 0.861 (P < .001). The performance of the model in assessing clinical disease activity was comparable to that of the present biomarkers: C-reactive protein and erythrocyte sedimentation rate. The 5 metabolites were significantly different among the patients and were valuable in the differentiation between CD and other chronic intestinal inflammatory diseases.

CONCLUSIONS

The combination of 5 serum metabolite biomarkers for the diagnosis of CD has the potential to provide an accurate, noninvasive, and inexpensive alternative to conventional tests and might be valuable for the differentiation from other diagnostically challenging intestinal inflammatory diseases.

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Affiliation(s)

Ruiqi Ma Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Yijun Zhu Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Xiaozhi Li Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Shixian Hu Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Danping Zheng Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Shanshan Xiong Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Shu Xu Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Liyuan Xiang Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Min Zhao Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Ce Tang Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Zhirong Zeng Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Minhu Chen Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Rui Feng Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Department of Gastroenterology, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Nanning, China

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Baldan-Martin M, Chaparro M, Gisbert JP. Systematic Review: Urine Biomarker Discovery for Inflammatory Bowel Disease Diagnosis. Int J Mol Sci 2023;24:10159. [PMID: 37373307 DOI: 10.3390/ijms241210159] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open

Calzadilla N, Comiskey SM, Dudeja PK, Saksena S, Gill RK, Alrefai WA. Bile acids as inflammatory mediators and modulators of intestinal permeability. Front Immunol 2022;13:1021924. [PMID: 36569849 PMCID: PMC9768584 DOI: 10.3389/fimmu.2022.1021924] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 10/26/2022] [Indexed: 12/12/2022] Open

Zheng L. New insights into the interplay between intestinal flora and bile acids in inflammatory bowel disease. World J Clin Cases 2022;10:10823-10839. [PMID: 36338232 PMCID: PMC9631134 DOI: 10.12998/wjcc.v10.i30.10823] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/08/2022] [Accepted: 09/16/2022] [Indexed: 02/05/2023] Open

Yan J, Chen Q, Tian L, Li K, Lai W, Bian L, Han J, Jia R, Liu X, Xi Z. Intestinal toxicity of micro- and nano-particles of foodborne titanium dioxide in juvenile mice: Disorders of gut microbiota-host co-metabolites and intestinal barrier damage. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022;821:153279. [PMID: 35074372 DOI: 10.1016/j.scitotenv.2022.153279] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 01/09/2022] [Accepted: 01/16/2022] [Indexed: 05/28/2023]

Park YE, Moon HS, Yong D, Seo H, Yang J, Shin TS, Kim YK, Kim JR, Lee YN, Kim YH, Kim JS, Cheon JH. Microbial changes in stool, saliva, serum, and urine before and after anti-TNF-α therapy in patients with inflammatory bowel diseases. Sci Rep 2022;12:6359. [PMID: 35428806 PMCID: PMC9012770 DOI: 10.1038/s41598-022-10450-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 03/30/2022] [Indexed: 11/08/2022] Open

Piestansky J, Olesova D, Matuskova M, Cizmarova I, Chalova P, Galba J, Majerova P, Mikus P, Kovac A. Amino acids in inflammatory bowel diseases: Modern diagnostic tools and methodologies. Adv Clin Chem 2022;107:139-213. [PMID: 35337602 DOI: 10.1016/bs.acc.2021.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Yu XH, Cao RR, Yang YQ, Lei SF. Identification of causal metabolites related to multiple autoimmune diseases. Hum Mol Genet 2021;31:604-613. [PMID: 34523675 DOI: 10.1093/hmg/ddab273] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 09/09/2021] [Accepted: 09/10/2021] [Indexed: 12/12/2022] Open

Yan Y, Ren S, Duan Y, Lu C, Niu Y, Wang Z, Inglis B, Ji W, Zheng Y, Si W. Gut microbiota and metabolites of α-synuclein transgenic monkey models with early stage of Parkinson's disease. NPJ Biofilms Microbiomes 2021;7:69. [PMID: 34475403 PMCID: PMC8413421 DOI: 10.1038/s41522-021-00242-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 08/02/2021] [Indexed: 02/03/2023] Open

Li N, Zhan S, Tian Z, Liu C, Xie Z, Zhang S, Chen M, Zeng Z, Zhuang X. Alterations in Bile Acid Metabolism Associated With Inflammatory Bowel Disease. Inflamm Bowel Dis 2021;27:1525-1540. [PMID: 33399195 DOI: 10.1093/ibd/izaa342] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Indexed: 12/12/2022]

Cui X, Zhang L, Su G, Kijlstra A, Yang P. Specific sweat metabolite profile in ocular Behcet's disease. Int Immunopharmacol 2021;97:107812. [PMID: 34091113 DOI: 10.1016/j.intimp.2021.107812] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 05/22/2021] [Accepted: 05/23/2021] [Indexed: 11/28/2022]

Zhou D, Zhu W, Sun T, Wang Y, Chi Y, Chen T, Lin J. iMAP: A Web Server for Metabolomics Data Integrative Analysis. Front Chem 2021;9:659656. [PMID: 34026726 PMCID: PMC8133432 DOI: 10.3389/fchem.2021.659656] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/06/2021] [Indexed: 12/11/2022] Open

Beck LC, Granger CL, Masi AC, Stewart CJ. Use of omic technologies in early life gastrointestinal health and disease: from bench to bedside. Expert Rev Proteomics 2021;18:247-259. [PMID: 33896313 DOI: 10.1080/14789450.2021.1922278] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]

Yamamoto M, Shanmuganathan M, Hart L, Pai N, Britz-McKibbin P. Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease. Metabolites 2021;11:metabo11040245. [PMID: 33921143 PMCID: PMC8071482 DOI: 10.3390/metabo11040245] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/29/2021] [Accepted: 04/10/2021] [Indexed: 12/14/2022] Open

Nong F, Luo S, Liang Y, Zhao Z, Xing S, Wen B, Zhou L. Evaluation of the effect of Dahuang-Mudan decoction on TNBS-induced colitis using UPLC-QTOF/MS-based metabolomic analysis. Biomed Chromatogr 2020;35:e5003. [PMID: 33063880 DOI: 10.1002/bmc.5003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/28/2020] [Accepted: 10/06/2020] [Indexed: 12/19/2022]

Benvenuti E, Pierini A, Gori E, Bartoli F, Erba P, Ruggiero P, Marchetti V. Serum amino acid profile in 51 dogs with immunosuppressant-responsive enteropathy (IRE): a pilot study on clinical aspects and outcomes. BMC Vet Res 2020;16:117. [PMID: 32321505 PMCID: PMC7178940 DOI: 10.1186/s12917-020-02334-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 04/05/2020] [Indexed: 12/11/2022] Open

Abstract

Background

Lower levels of tryptophan (TRP) have been identified in people with inflammatory bowel disease and in dogs with protein-losing enteropathy (PLE). No data on serum amino acids (AAs) but some on plasma in canine immunosuppressant-responsive enteropathy (IRE) are available. The aim of this study is to compare serum AAs between healthy and IRE dogs, considering clinicopathological variables and follow-up.

Results

Twenty-six healthy control dogs (CD) and 51 IRE dogs were included. IRE was diagnosed after the exclusion of extra-intestinal diseases and food and antibiotic responsive enteropathies. The canine chronic enteropathy clinical activity index (CCECAI) was assessed at presentation and during the clinical follow-up. In CD and IRE dogs, 19 different serum AAs were measured. IRE dogs were classified into responders, partial responders and non-responders, based on CCECAI after 1 month, and divided into PLE and non-PLE, based on albumin level. IRE dogs showed lower L-Tyrosine (TYR), L-Phenylalanine (PHE) and TRP (p < 0.001) and higher L-Serine (SER), L-Glutamic acid (GLU), L-Arginine (p < 0.001), L-Threonine (p = 0.013), Proline (p = 0.044), L-Cysteine (p = 0.003), L-Valine (p = 0.018), L-Lysine (p = 0.01) and L-Isoleucine (p = 0.005) than CDs. PLE dogs showed lower L-Histidine (HIS) (p = 0.008), PHE (p = 0.005) and TRP (p = 0.005) than non-PLE dogs. In IRE dogs, median GLU was significantly lower in dogs with BCS 3/9 than BCS 5/9 category (p = 0.036). Total protein was positively correlated with PHE and TRP (both p = 0.031, r = 0.30) and albumin was positively correlated with HIS (p = 0.025, r = 0.31), PHE and TRP (both p = 0.001, r = 0.46). HIS (p = 0.041), PHE (p = 0.047) and TRP (p = 0.044) concentrations were significantly lower in non-responders than in responders and partial responders.

Conclusions

This study may suggest further investigation on serum, HIS, PHE, TRP and TYR as markers of intestinal disease and proposed HIS, PHE and TRP as prognostic marker for response to therapy.

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Godin JP, Martin FP, Breton I, Schoepfer A, Nydegger A. Total and activity-induced energy expenditure measured during a year in children with inflammatory bowel disease in clinical remission remain lower than in healthy controls. Clin Nutr 2020;39:3147-3152. [PMID: 32147199 DOI: 10.1016/j.clnu.2020.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 02/04/2020] [Accepted: 02/05/2020] [Indexed: 02/07/2023]

Filimoniuk A, Daniluk U, Samczuk P, Wasilewska N, Jakimiec P, Kucharska M, Lebensztejn DM, Ciborowski M. Metabolomic profiling in children with inflammatory bowel disease. Adv Med Sci 2020;65:65-70. [PMID: 31901795 DOI: 10.1016/j.advms.2019.12.009] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 09/25/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023]

Synbiotic supplementation with prebiotic green banana resistant starch and probiotic Bacillus coagulans spores ameliorates gut inflammation in mouse model of inflammatory bowel diseases. Eur J Nutr 2020;59:3669-3689. [PMID: 32067099 PMCID: PMC7669818 DOI: 10.1007/s00394-020-02200-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/06/2020] [Indexed: 02/07/2023]

Abstract

Purpose

The research goal is to develop dietary strategies to help address the growing incidence of inflammatory bowel diseases (IBD). This study has investigated the effectiveness of green banana resistant starch (GBRS) and probiotic Bacillus coagulans MTCC5856 spores for the amelioration of dextran-sulfate sodium (DSS)-induced colitis in mice.

Methods

Eight-week-old C57BL/6 mice were fed standard rodent chow diet supplemented with either B. coagulans, GBRS or its synbiotic combination. After 7 days supplementation, colitis was induced by adding 2% DSS in drinking water for 7 days while continuing the supplemented diets. Animal health was monitored and after 14 days all animals were sacrificed to measure the biochemical and histochemical changes associated with each supplement type.

Results

The disease activity index and histological damage score for DSS-control mice (6.1, 17.1, respectively) were significantly higher (p < 0.0001) than the healthy mice. Synbiotic supplementation alleviated these markers (− 67%, − 94% respectively) more adequately than B. coagulans (− 52%, − 58% respectively) or GBRS (− 57%, − 26%, respectively) alone. Compared to DSS-control synbiotic supplementation significantly (p < 0.0001) maintained expressions of tight junction proteins. Moreover, synbiotic effects accounted for ~ 40% suppression of IL-1β and ~ 29% increase in IL-10 levels in serum while also reducing C-reactive protein (− 37%) compared to that of the DSS-control. While, B. coagulans alone could not induce additional levels of short-chain fatty acid (SCFA) production beyond the caecum, the synbiotic combination with GBRS resulted in substantial increased SCFA levels across the whole length of the colon.

Conclusion

The synbiotic supplementation with B. coagulans and GBRS ameliorated the overall inflammatory status of the experimental IBD model via synergistic functioning. This supports researching its application in mitigating inflammation in human IBD.

Electronic supplementary material

The online version of this article (10.1007/s00394-020-02200-9) contains supplementary material, which is available to authorized users.

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Mucosal Metabolomic Profiling and Pathway Analysis Reveal the Metabolic Signature of Ulcerative Colitis. Metabolites 2019;9:metabo9120291. [PMID: 31783598 PMCID: PMC6950742 DOI: 10.3390/metabo9120291] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/21/2019] [Accepted: 11/25/2019] [Indexed: 12/12/2022] Open

Profiling of Amino Acids in Urine Samples of Patients Suffering from Inflammatory Bowel Disease by Capillary Electrophoresis-Mass Spectrometry. Molecules 2019;24:molecules24183345. [PMID: 31540027 PMCID: PMC6767150 DOI: 10.3390/molecules24183345] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 09/09/2019] [Accepted: 09/11/2019] [Indexed: 12/12/2022] Open

Abstract

Urine represents a convenient biofluid for metabolomic studies due to its noninvasive collection and richness in metabolites. Here, amino acids are valuable biomarkers for their ability to reflect imbalances of different biochemical pathways. An impact of amino acids on pathology, prognosis and therapy of various diseases, including inflammatory bowel disease (IBD), is therefore the subject of current clinical research. This work is aimed to develop a capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) method for the quantification of the 20 proteinogenic amino acids in human urine samples obtained from patients suffering from IBD and treated with thiopurines. The optimized CE-MS/MS method, with minimum sample preparation (just “dilute and shoot”), exhibited excellent linearity for all the analytes (coefficients of determination were higher than 0.99), with inter-day and intra-day precision yielding relative standard deviations in the range of 0.91–15.12% and with accuracy yielding relative errors in the range of 85.47–112.46%. Total analysis time, an important parameter for the sample throughput demanded in routine practice, was shorter in ca. 17% when compared to established CE-MS methods. Favorable performance of the proposed CE-MS/MS method was also confirmed by the comparison with corresponding ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) method. Consistent data for the investigated amino acid metabolome were obtained using both methods. For the first time, the amino acid profiling by CE-MS approach was applied on the clinical IBD samples. Here, significant differences observed in the concentration levels of some amino acids between IBD patients undergoing thiopurine treatment and healthy volunteers could result from the simultaneous action of the disease and the corresponding therapy. These findings indicate that amino acids analysis could be a valuable tool for the study of mechanism of the IBD treatment by thiopurines.

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Shinde T, Perera AP, Vemuri R, Gondalia SV, Karpe AV, Beale DJ, Shastri S, Southam B, Eri R, Stanley R. Synbiotic Supplementation Containing Whole Plant Sugar Cane Fibre and Probiotic Spores Potentiates Protective Synergistic Effects in Mouse Model of IBD. Nutrients 2019;11:E818. [PMID: 30979002 PMCID: PMC6521199 DOI: 10.3390/nu11040818] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/09/2019] [Accepted: 04/10/2019] [Indexed: 12/20/2022] Open

Abstract

Inflammatory bowel diseases (IBD) are a chronic inflammatory disorders with increasing global incidence. Synbiotic, which is a two-point approach carrying probiotic and prebiotic components in mitigating inflammation in IBD, is thought to be a pragmatic approach owing to the synergistic outcomes. In this study, the impacts of dietary supplementation with probiotic Bacillus coagulans MTCC5856 spores (B. coagulans) and prebiotic whole plant sugar cane fibre (PSCF) was assessed using a murine model of IBD. Eight-week-old C57BL/6 mice were fed a normal chow diet supplemented with either B. coagulans, PSCF or its synbiotic combination. After seven days of supplementation, colitis was induced with dextran sulfate sodium (DSS) in drinking water for seven days during the continuation of the supplemented diets. Synbiotic supplementation ameliorated disease activity index and histological score (-72%, 7.38, respectively), more effectively than either B. coagulans (-47%, 10.1) and PSCF (-53%, 13.0) alone. Synbiotic supplementation also significantly (p < 0.0001) prevented the expression of tight junction proteins and modulated the altered serum IL-1β (-40%), IL-10 (+26%), and C-reactive protein (CRP) (-39%) levels. Synbiotic supplementations also raised the short-chain fatty acids (SCFA) profile more extensively compared to the unsupplemented DSS-control. The synbiotic health outcome effect of the probiotic and prebiotic combinations may be associated with a synergistic direct immune-regulating efficacy of the components, their ability to protect epithelial integrity, stimulation of probiotic spores by the prebiotic fibre, and/or with stimulation of greater levels of fermentation of fibres releasing SCFAs that mediate the reduction in colonic inflammation. Our model findings suggest synbiotic supplementation should be tested in clinical trials.

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Sugihara K, Morhardt TL, Kamada N. The Role of Dietary Nutrients in Inflammatory Bowel Disease. Front Immunol 2019;9:3183. [PMID: 30697218 PMCID: PMC6340967 DOI: 10.3389/fimmu.2018.03183] [Citation(s) in RCA: 124] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 12/27/2018] [Indexed: 12/22/2022] Open

Godoy-Vitorino F, Ortiz-Morales G, Romaguera J, Sanchez MM, Martinez-Ferrer M, Chorna N. Discriminating high-risk cervical Human Papilloma Virus infections with urinary biomarkers via non-targeted GC-MS-based metabolomics. PLoS One 2018;13:e0209936. [PMID: 30592768 PMCID: PMC6310238 DOI: 10.1371/journal.pone.0209936] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 12/13/2018] [Indexed: 02/05/2023] Open

Wei R, Ross AB, Su M, Wang J, Guiraud SP, Draper CF, Beaumont M, Jia W, Martin FP. Metabotypes Related to Meat and Vegetable Intake Reflect Microbial, Lipid and Amino Acid Metabolism in Healthy People. Mol Nutr Food Res 2018;62:e1800583. [PMID: 30098305 DOI: 10.1002/mnfr.201800583] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 07/25/2018] [Indexed: 01/05/2023]

Metabolic phenotyping for understanding the gut microbiome and host metabolic interplay. Emerg Top Life Sci 2017;1:325-332. [PMID: 33525773 DOI: 10.1042/etls20170079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 11/08/2017] [Accepted: 11/08/2017] [Indexed: 01/08/2023]