Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology

Abstract

Inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease, are chronic pathologies associated with a deregulated immune response in the intestinal mucosa, and they are triggered by environmental factors in genetically susceptible individuals. Exogenous glucocorticoids (GCs) are widely used as anti-inflammatory therapy in IBDs. In the past, patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission. However, this treatment often results in detrimental side effects. This downside drove the development of second generation GCs and more precise (non-systemic) drug-delivery methods. Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects. The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment. A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment. In this review, we examine the clinical characteristics of treatment with GCs, followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs. This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.

Single-Nucleotide Nr3C1 Gene Polymorphisms Affect Glucocorticosteroid Treatment Efficacy In Patients With Pemphigus Vulgaris

“…Based on published data, we chose 10 SNPs reported to affect GC e cacy in patients with various diseases: rs17209237, rs11745958, rs33388, rs7701443, rs41423247, rs6189, rs6190, rs6195, rs6196, and rs6198 [10], [11], [12], [13], [14], [15], [16], [17]. Whole blood samples from all patients were collected in tubes containing ethylenediamine tetra-acetic acid (EDTA) and sent to our Biotechnology Center for TaqMan SNP genotyping [18].…”

“…GCs exert their biological effects via GC receptor (GR), which regulates the expression of GC-target genes [8], [9]. Earlier studies reported that several NR3C1 single nucleotide polymorphisms (SNPs) (rs6189, rs6190, rs6195, rs6196, rs6198, and rs41423247) might correlate with GC e cacy in patients with in ammatory bowel disease, rheumatoid arthritis, asthma, and idiopathic nephrotic syndrome [10], [11], [12], [13], [14], [15], [16]. For PV patients, Fang et al [17] were the rst to report associations between NR3C1 SNPs and GC e cacy; rs11745958 C/T and rs17209237 A/G may be associated with increased risks of GC resistance, but rs33388 A/T and rs7701443 A/G with decreased risks.…”

Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches

“…Associations with cellular proliferation and antiinflammatory responses (47) Exogenous glucocorticoids are heavily used as antiinflammatory therapy for IBD (48,49)) ATG16L1, an autophagy related gene, was downregulated in patients who do not respond to glucocorticoid treatment (50,51) Transcriptionally regulates NFKβ1, a SNP affected gene in ulcerative colitis (52,53) VDR (Vitamin D Receptor)…”

Decoding the Language of Microbiomes: Leveraging Patterns in 16S Public Data using Word-Embedding Techniques and Applications in Inflammatory Bowel Disease

“…Among these pathways, both steroid metabolism and biosynthesis were found to be associated with IBD. Steroids are a well-known and commonly utilized treatment for patients with active Crohn's disease (52). Enrichment in steroid metabolism in the gut microbiome could be reflective of an increase in steroid availability due to treatment.…”