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Biomarkers of human gastrointestinal tract regions

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Abstract

Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations. We analyzed the gene expression signature of antrum, duodenum, jejunum, ileum, and transverse colon biopsies using a biostatistical method based on a multivariate and univariate approach to identify region-selective genes. One hundred sixty-six genes were found responsible for distinguishing the five regions considered. Nineteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion and six novel genes. Moreover, by crossing these genes with those retrieved from an existing data set of gene expression in the intestine of ulcerative colitis and Crohn’s disease patients, we identified genes that might be biomarkers of Crohn’s and/or ulcerative colitis in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. This study furnishes the first map of gene expression along the healthy human gastrointestinal tract. Furthermore, the approach implemented here, and validated by retrieving known gene profiles, allowed the identification of promising new leads in both healthy and disease states.

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Acknowledgments

We thank Maribelle Herranz-Garcia for technical support during tissue sampling and Nadine Porta, Muriel Fiaux, Dominique Donnicola, and Frederic Raymond for technical support with the microarray analysis. We are also thankful to Robert Mansourian for valuable contributions to the statistics and to Ziding Zhang for fold recognition analysis. We are grateful to Anne Donnet, Magali Faure, Clara Garcia-Rodenas, Athula Herath, and Karine Vidal for constructive scientific discussion.

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Author notes

  1. Grigorios Fotopoulos

    Present address: Novartis Consumer Health, 1260, Nyon 1, Switzerland

  2. Sofiane Lariani

    Present address: Nestlé R&D Centre York, York, UK

Authors and Affiliations

  1. Department of Nutrition and Health, Nestlé Research Center, Vers chez les Blanc, 1000, Lausanne 26, Switzerland

    Elena Maria Comelli, Grigorios Fotopoulos, Christine Cherbut & Irène Corthésy-Theulaz

  2. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, FitzGerald Building, Room 308A, Toronto, ON, M5S 3E2, Canada

    Elena Maria Comelli

  3. Department of BioAnalytical Science, Nestlé Research Center, Vers chez les Blanc, 1000, Lausanne 26, Switzerland

    Sofiane Lariani, Marie-Camille Zwahlen, James Anthony Holzwarth & Martin Grigorov

  4. Department of Gastroenterology, University Hospital CHUV, 1011, Lausanne, Switzerland

    Gian Dorta

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  1. Elena Maria Comelli
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Correspondence to Elena Maria Comelli.

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Comelli, E.M., Lariani, S., Zwahlen, MC. et al. Biomarkers of human gastrointestinal tract regions. Mamm Genome 20, 516–527 (2009). https://doi.org/10.1007/s00335-009-9212-7

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