Colon Epithelial MicroRNA Network in Fatty Liver.

Background & Aims: Intestinal barrier alterations are associated with fatty liver (FL) and metabolic syndrome (MetS), but microRNA (miR) signaling pathways in MetS-FL pathogenesis remain unclear. This study investigates an epithelial-focused miR network in colorectal cell models based on the previously reported MetS-FL miR trio of hsa-miR-142-3p, hsa-miR-18b, and hsa-miR-890. Methods: Each miR mimic construct of MetS-FL miR trio was transfected into human colorectal cells, CRL-1790 or Caco-2. Global miRNome changes posttransfection were profiled (nCounter® Human v3 miRNA, NanoString Technologies). Changes in barrier (transepithelial electrical resistance, TEER) and epithelial cell junction structure (Occludin and Zona Occludens-1/ZO-1 immunofluorescence staining-confocal microscopy) were examined pre- and posttransfection in Caco-2 cell monolayers. A signaling network was constructed from the MetS-FL miR trio, MetS-FL miR-induced colorectal miRNome changes, ZO-1, and Occludin. Results: Transfection of CRL-1790 cells with each MetS-FL miR mimic led to global changes in the cellular miRNome profile, with 288 miRs being altered in expression by more than twofold. Eleven miRs with known cytoskeletal and metabolic roles were commonly altered in expression by all three miR mimics. Transfection of Caco-2 cell monolayers with each MetS-FL miR mimic induced barrier-associated TEER variations and led to structural modifications of ZO-1 and Occludin within epithelial cell junctions. Pathway analysis incorporating the MetS-FL miR trio, eleven common target miRs, ZO-1, and Occludin revealed a signaling network centered on TNF and AKT2, which highlights injury, inflammation, and hyperplasia. Conclusions: Colon-specific changes in epithelial barriers, cell junction structure, and a miRNome signaling network are described from functional studies of a MetS-FL miR trio signature.

Gender and Weight Influence Quality of Life in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and bowel dysfunction in the absence of structural abnormality. Diagnosis can be challenging and often leads to extensive medical tests, non-effective therapeutic modalities, and reduced quality of life (QOL). Identifying factors associated with dysfunction have the potential to enhance outcomes. Participants with IBS (n = 41) and healthy volunteers (n = 74) were recruited into this cross-sectional, descriptive, natural history protocol at the National Institute of Health, Clinical Center. Demographic characteristics were self-reported. QOL was assessed with the Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire. Statistical analysis included descriptive statistics, factorial ANOVA, and multiple regression. Individuals with IBS reported lower QOL scores across all QOL-subscales compared to healthy controls. Normal-weight women and overweight men with IBS reported the greatest QOL impairment. Body fat percent had confounding effects on the relationship between IBS and QOL. The disparity between QOL scores in participants with IBS by both gender and weight groups may reflect different social pressures perceived by normal and overweight women and men. These findings enhance the recognition of the disparities in patients with chronic symptoms and thereby lead to personalized assessment and interventions to improve their QOL.