Comparative expression profiling in the intestine of patients with Giardia‐induced postinfectious functional gastrointestinal disorders
Open Access
- 11 May 2020
- journal article
- research article
- Published by Wiley in Neurogastroenterology & Motility
- Vol. 32 (9), e13868
- https://doi.org/10.1111/nmo.13868
Abstract
Background A Giardia outbreak in Bergen, Norway, caused postinfectious functional gastrointestinal disorders (PI‐FGIDs). Despite the devastating effects of this outbreak, it presented a unique chance to investigate the implication on the dysregulation of genetic pathways in PI‐FGID. Methods We performed the first comparative expression profiling of miRNAs and their potential target genes in microdissected rectal biopsies from 20 Giardia‐induced PI‐FGID patients vs 18 healthy controls by nCounter analysis. Subsequently, candidates were validated on protein level by immunostaining. Key Results miRNA profiling on rectal biopsy samples from 5 diarrhea‐predominant PI‐IBS cases compared to 10 healthy controls revealed differential expression in the epithelial layer. The top five regulated miRNAs were implicated in GI disease, inflammatory response, and immunological disease. Subsequently, these miRNAs and 100 potential mRNA targets were examined in 20 PI‐FGID cases and 18 healthy controls in both the mucosal epithelium and the lamina propria. Although deregulation of the selected miRNAs could not be verified in the larger sample set, mRNAs involved in barrier function were downregulated in the epithelium. Pro‐inflammatory genes and genes implicated in epigenetic modifications were upregulated in the lamina propria. Immunostaining for selected candidates on 17 PI‐FGID cases and 16 healthy controls revealed increased tryptase levels as well as a decreased and aberrant subcellular expression of occludin. Conclusions and Inferences Genes relevant to immune and barrier function as well as stress response and epigenetic modulation are differentially expressed in PI‐FGIDs and may contribute to disease manifestation.Funding Information
- Instituto de Salud Carlos III (CP18/00116)
- Fritz Thyssen Stiftung (Az 20.16.0.063MN)
This publication has 70 references indexed in Scilit:
- Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural courseBMC Gastroenterology, 2013
- Evaluation of normalization methods in mammalian microRNA-Seq dataRNA, 2012
- NanoStringNorm: an extensible R package for the pre-processing of NanoString mRNA and miRNA dataBioinformatics, 2012
- Irritable bowel syndrome - An inflammatory disease involving mast cellsAsia Pacific Allergy, 2011
- Increased Immunoendocrine Cells in Intestinal Mucosa of Postinfectious Irritable Bowel Syndrome Patients 3 Years after Acute Shigella Infection - An Observation in a Small Case Control StudyYonsei Medical Journal, 2010
- MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndromeGut, 2009
- Hepatocyte Nuclear Factor 4α, a Key Factor for Homeostasis, Cell Architecture, and Barrier Function of the Adult Intestinal EpitheliumMolecular and Cellular Biology, 2009
- Development of functional gastrointestinal disorders after Giardia lambliainfectionBMC Gastroenterology, 2009
- Role for protease activity in visceral pain in irritable bowel syndromeJCI Insight, 2007
- Hepatocyte nuclear factor 4α orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liverProceedings of the National Academy of Sciences of the United States of America, 2006