Comparative expression profiling in the intestine of patients with Giardia‐induced postinfectious functional gastrointestinal disorders

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.

Age and Giardia intestinalis Infection Impact Canine Gut Microbiota

“…Epidemiological studies have linked G. intestinalis outbreaks to important post-infectious complications in humans, especially the development of irritable bowel syndrome (IBS) after the clearance of the parasite [ 41 , 93 , 96 ]. In addition, dogs are able to develop an IBS-like condition, similar to that described in humans [ 97 ].…”

The enteric nervous system in gastrointestinal disease etiology

“…Although there is a vast amount of literature focusing on visceral hypersensitivity acting through extrinsic afferent pathways [152][153][154][155][156][157][158][159], inflammatory mediators can also modify ENS components, thereby facilitating the development of DGBIs [160,161]. Increased infiltration and activation of mast cells [162][163][164][165], together with elevated levels of mast cell mediators, including histamine and proteases, but also relevant miRNAs and neurotrophins have been substantiated in DGBIs [166][167][168][169]. A positive correlation between the number of mast cells in close contact with enteric neurons and the degree of abdominal pain was demonstrated in IBS patients [170], albeit, this is not necessarily reflective of a causal relationship.…”

Overlap between irritable bowel syndrome and hypermobileEhlers–Danlossyndrome: An unexplored clinical phenotype?

“…These mechanisms include somatization, and physiological changes, such as visceral hypersensitivity, autonomic dysfunction, psychological factors such as anxiety and depression, abnormalities in motility, increased intestinal permeability, low-grade inflammation, diet, altered microbiome, and abnormal gut-brain interactions. (El-Salhy & Gundersen, 2015;Martínez et al, 2020;Mayer, Naliboff, & Chang, 2001;Peleman et al, 2017;Simren et al, 2018;Wang et al, 2020;Waring, Chui, Japp, Nicol, & Ford, 2004;Zhou, Zhang, & Verne, 2009). The combination of these mechanisms and how they result in symptoms of IBS can be described using the biopsychosocial model of IBS (Figure 1, kindly reproduced with permission from Elsevier).…”