Inflammatory bowel disease represents a group of chronic disorders that affect one or more parts of the intestine. Although recently the incidence of inflammatory bowel disease has noticeably increased, its aetiology is still unclear. No specific pathogen has been defined as a causative agent. Serological biomarkers have been recently proposed for diagnosis, but they remain untested in clinical applications. Moreover, current diagnostic and monitoring practices for inflammatory bowel disease are very invasive. Therefore, accurate tools for the early diagnosis, and in particular non-invasive strategies are needed. One area of recent interest is the relationship between the metabolome and microbiota in terms of inflammatory bowel disease pathogenesis and intervention strategies. Direct analysis of metabolites and their interaction with the gut microbial species is a rapidly growing field of research. In this context, metabolomics could represent a useful approach to understand possible pathological mechanisms or metabolite modification in different pathways. Metabolomics is based on the quantitative measurement of dynamic metabolic changes in living systems in response to physiological stimuli or genetic modifications, nutrients and drugs. Thanks to the comprehensive study of low molecular weight metabolites (<1500 Da) in biofluids and in tissues, metabolomics ensures the characterization of the metabolic phenotype of a living organism. In this work, the polar and the lipid metabolite profile of faecal and plasma samples of patients affected by inflammatory bowel disease and healthy patients has been studied by high resolution liquid chromatography coupled with several technological platforms such as a triple quadrupole, a quadrupole time of flight mass spectrometry and an ion mobility prior to multivariate statistical data analysis. By these means, differences between Crohn’s disease, ulcerative colitis and control samples were investigated. Results of discriminant analysis were considered with the aim to find the relevant metabolites unique for each class. The results highlight differences in the metabolite profile between the pathological and the control samples. In faecal samples, the most discriminant metabolites for both IBD classes were diacylglycerols, phosphatidylcholines triacylglycerols and tetra pyrrole compounds. Furthermore, plasma samples results showed modification of the lysophosphatidylcholine and phosphatidylcholine pathways strictly related to the arachidonic acid response. These results highlight similarity in the metabolic alteration occurring in both ulcerative colitis and Crohn’s disease when compared to healthy controls. Modification to the endocannabinoid system were also found regarding the ulcerative colitis plasma and faecal samples. All the lipid results were correlated with the targeted analysis of the polar metabolites profile. In conclusion, the application of metabolomics to faecal and plasma samples of IBD patients allows for the identification of metabolites that can be used as possible indicators of metabolic pathways implicated in the onset of these pathologies.

INFLAMMATORY BOWEL DISEASE STUDY: A METABOLOMICS APPROACH

MURGIA, ANTONIO
2018-02-13

Abstract

Inflammatory bowel disease represents a group of chronic disorders that affect one or more parts of the intestine. Although recently the incidence of inflammatory bowel disease has noticeably increased, its aetiology is still unclear. No specific pathogen has been defined as a causative agent. Serological biomarkers have been recently proposed for diagnosis, but they remain untested in clinical applications. Moreover, current diagnostic and monitoring practices for inflammatory bowel disease are very invasive. Therefore, accurate tools for the early diagnosis, and in particular non-invasive strategies are needed. One area of recent interest is the relationship between the metabolome and microbiota in terms of inflammatory bowel disease pathogenesis and intervention strategies. Direct analysis of metabolites and their interaction with the gut microbial species is a rapidly growing field of research. In this context, metabolomics could represent a useful approach to understand possible pathological mechanisms or metabolite modification in different pathways. Metabolomics is based on the quantitative measurement of dynamic metabolic changes in living systems in response to physiological stimuli or genetic modifications, nutrients and drugs. Thanks to the comprehensive study of low molecular weight metabolites (<1500 Da) in biofluids and in tissues, metabolomics ensures the characterization of the metabolic phenotype of a living organism. In this work, the polar and the lipid metabolite profile of faecal and plasma samples of patients affected by inflammatory bowel disease and healthy patients has been studied by high resolution liquid chromatography coupled with several technological platforms such as a triple quadrupole, a quadrupole time of flight mass spectrometry and an ion mobility prior to multivariate statistical data analysis. By these means, differences between Crohn’s disease, ulcerative colitis and control samples were investigated. Results of discriminant analysis were considered with the aim to find the relevant metabolites unique for each class. The results highlight differences in the metabolite profile between the pathological and the control samples. In faecal samples, the most discriminant metabolites for both IBD classes were diacylglycerols, phosphatidylcholines triacylglycerols and tetra pyrrole compounds. Furthermore, plasma samples results showed modification of the lysophosphatidylcholine and phosphatidylcholine pathways strictly related to the arachidonic acid response. These results highlight similarity in the metabolic alteration occurring in both ulcerative colitis and Crohn’s disease when compared to healthy controls. Modification to the endocannabinoid system were also found regarding the ulcerative colitis plasma and faecal samples. All the lipid results were correlated with the targeted analysis of the polar metabolites profile. In conclusion, the application of metabolomics to faecal and plasma samples of IBD patients allows for the identification of metabolites that can be used as possible indicators of metabolic pathways implicated in the onset of these pathologies.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/255960
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