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Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exis...

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Autores principales: Grozić, Aleksandra, Coker, Keaton, Dussik, Christopher M., Sabir, Marya S., Sabir, Zhela, Bradley, Arianna, Zhang, Lin, Park, Jin, Yale, Steven, Kaneko, Ichiro, Hockley, Maryam, Harris, Lucinda A., Lunsford, Tisha N., Sandrin, Todd R., Jurutka, Peter W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584396/
https://www.ncbi.nlm.nih.gov/pubmed/36264926
http://dx.doi.org/10.1371/journal.pone.0275683
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author Grozić, Aleksandra
Coker, Keaton
Dussik, Christopher M.
Sabir, Marya S.
Sabir, Zhela
Bradley, Arianna
Zhang, Lin
Park, Jin
Yale, Steven
Kaneko, Ichiro
Hockley, Maryam
Harris, Lucinda A.
Lunsford, Tisha N.
Sandrin, Todd R.
Jurutka, Peter W.
author_facet Grozić, Aleksandra
Coker, Keaton
Dussik, Christopher M.
Sabir, Marya S.
Sabir, Zhela
Bradley, Arianna
Zhang, Lin
Park, Jin
Yale, Steven
Kaneko, Ichiro
Hockley, Maryam
Harris, Lucinda A.
Lunsford, Tisha N.
Sandrin, Todd R.
Jurutka, Peter W.
author_sort Grozić, Aleksandra
collection PubMed
description Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for “IBS mimickers” such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism.
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spelling pubmed-95843962022-10-21 Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D Grozić, Aleksandra Coker, Keaton Dussik, Christopher M. Sabir, Marya S. Sabir, Zhela Bradley, Arianna Zhang, Lin Park, Jin Yale, Steven Kaneko, Ichiro Hockley, Maryam Harris, Lucinda A. Lunsford, Tisha N. Sandrin, Todd R. Jurutka, Peter W. PLoS One Research Article Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for “IBS mimickers” such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism. Public Library of Science 2022-10-20 /pmc/articles/PMC9584396/ /pubmed/36264926 http://dx.doi.org/10.1371/journal.pone.0275683 Text en © 2022 Grozić et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Grozić, Aleksandra
Coker, Keaton
Dussik, Christopher M.
Sabir, Marya S.
Sabir, Zhela
Bradley, Arianna
Zhang, Lin
Park, Jin
Yale, Steven
Kaneko, Ichiro
Hockley, Maryam
Harris, Lucinda A.
Lunsford, Tisha N.
Sandrin, Todd R.
Jurutka, Peter W.
Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D
title Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D
title_full Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D
title_fullStr Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D
title_full_unstemmed Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D
title_short Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D
title_sort identification of putative transcriptomic biomarkers in irritable bowel syndrome (ibs): differential gene expression and regulation of tph1 and sert by vitamin d
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584396/
https://www.ncbi.nlm.nih.gov/pubmed/36264926
http://dx.doi.org/10.1371/journal.pone.0275683
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