Inflammatory Bowel Diseases and Non-Alcoholic Fatty Liver Disease: Piecing a Complex Puzzle Together.

Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are systemic and multifaceted disorders which affect other organs in addition to the gastrointestinal tract in up to 50% of cases. Extraintestinal manifestations may present before or after IBD diagnosis and negatively impact the intestinal disease course and patients' quality of life, often requiring additional diagnostic evaluations or specific treatments. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Current evidence shows an increased prevalence of NAFLD (and its more advanced stages, such as liver fibrosis and steatohepatitis) in IBD patients compared to the general population. Many different IBD-specific etiopathogenetic mechanisms have been hypothesized, including chronic inflammation, malabsorption, previous surgical interventions, changes in fecal microbiota, and drugs. However, the pathophysiological link between these two diseases is still poorly understood. In this review, we aim to provide a comprehensive overview of the potential mechanisms which have been investigated so far and highlight open issues still to be addressed for future studies.

Cytolethal distending toxin modulates cell differentiation and elicits epithelial to mesenchymal transition.

BACKGROUND: The bacterial genotoxin, cytolethal distending toxin (CDT), causes DNA damage in host cells, a risk factor for carcinogenesis. Previous studies have shown that CDT induces phenotypes reminiscent of epithelial to mesenchymal transition (EMT), a process involved in cancer initiation and progression. METHODS: We investigated different steps of EMT in response to Helicobacter hepaticus CDT and its active CdtB subunit using in vivo and in vitro models. RESULTS: Most of the steps of the EMT process were induced by CDT/CdtB and observed throughout the study in murine and epithelial cell culture models. CdtB induced cell-cell junctions' disassembly, causing individualization of cells and acquisition of a spindle-like morphology. The key transcriptional regulators of EMT (SNAIL1 and ZEB1) and some EMT markers were upregulated at both RNA and protein levels in response to CDT/CdtB. CdtB increased the expression and proteolytic activity of matrix metalloproteinases, as well as cell migration. A range of these results were confirmed in Helicobacter hepaticus infected and xenograft murine models. In addition, colibactin, a genotoxic metabolite produced by Escherichia coli, induced EMT-like effects in cell culture. CONCLUSION: Overall, these data show that infection with genotoxin-producing bacteria elicits EMT process activation, supporting their role in tumorigenesis.