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Interference with the lower gut-liver axis induces remission of primary sclerosing cholangitis in a patient with ulcerative colitis.

ABSTRACT: The gut-liver axis describes the complex interactions between gut microbiota, the small and large bowel, the immune system and the liver. Current evidence associates abnormalities within the gut-liver axis with liver disease such as primary sclerosing cholangitis (PSC). PSC is believed to be an immune-mediated disease though the exact mechanism of its pathogenesis remains unknown. Here, we report a case of a 66 -year-old woman with treatment-resistant ulcerative colitis and PSC which continued to be active following subtotal colectomy. Interestingly, her PSC achieved full remission after proctectomy for treatment-resistant proctitis in the rectal stump. This case report supports existing hypotheses that PSC is an immune-mediated disease triggered by antigens within the gut. More notably, it suggests the yet unidentified pathogens may be localised to the lower gastrointestinal tract including the rectum.

SUBMITTER: Ong J

PROVIDER: S-EPMC6267462 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Interference with the lower gut-liver axis induces remission of primary sclerosing cholangitis in a patient with ulcerative colitis.

Ong John J Mebarek Leila L Bath Michael M Swift Carla C Javaid Babur B Patel Jenish J Al-Naeeb Yasseen Y

BMJ open gastroenterology 20181114 1

The gut-liver axis describes the complex interactions between gut microbiota, the small and large bowel, the immune system and the liver. Current evidence associates abnormalities within the gut-liver axis with liver disease such as primary sclerosing cholangitis (PSC). PSC is believed to be an immune-mediated disease though the exact mechanism of its pathogenesis remains unknown. Here, we report a case of a 66 -year-old woman with treatment-resistant ulcerative colitis and PSC which continued t ...[more]

PMID: 30555709

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Project description:ObjectivesThe clinical/colonoscopic features of ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC), the prognostic impact of UC, and the utility of UC screening in PSC patients are unknown. We characterized UC associated with PSC and assessed UC's impact on the prognosis of PSC and the importance of colonoscopic UC screening in PSC patients.MethodsWe retrospectively analyzed the cases of 77 patients treated for PSC at a single center (April 2000-July 2019). We reviewed the clinical/colonoscopic profiles of the concurrent UC patients and compared the clinical profiles, survival, and primary causes of death between the patients with/without UC (n = 35/n = 42). The details of all patients' colonoscopies were reviewed.ResultsThe concurrent UC group: 17 men, 18 women, diagnosed with PSC at the mean (SD) age of 36 (17) years; 21 patients (60%) had no UC symptoms. Colonoscopy revealed pancolitis in all patients, predominantly affecting the right-sided colon in 30 patients (86%). Lesions were scattered. Backwash ileitis (n = 13, 37%) and rectal sparing (n = 18, 51%) were observed. Most patients had mild UC; some had moderate or more severe UC (median Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score 2; range, 1-5). Ludwig's stage determined by liver biopsy did not correlate with the Mayo endoscopic score for UC. The patients with UC were diagnosed with PSC at a significantly younger age than those without UC (mean (SD), 36 [17] years vs. 55 [19] years, p < 0.0001) and had a significantly higher 5-year survival rate (97.1% vs. 70.5%, p = 0.0028). UC was detected in 19 of 34 asymptomatic patients (56%) who underwent colonoscopy screening.ConclusionsOur cohort's clinical/colonoscopic features of UC associated with PSC are more moderate or severe UC than previous cases. The coexistence of UC might affect the prognosis of PSC. In this regard, colonoscopy in PSC patients is an important examination for determining prognosis. There is also asymptomatic UC in patients with PSC. In this regard, screening for colonoscopy in PSC patients is essential. When a diagnosis of PSC is made, immediate colonoscopy is a priority with UC complications in mind.

Project description:Background: Patients suffering from primary sclerosing cholangitis (PSC) often also have ulcerative colitis (UC). Cross-disease genetic and microbiome studies across PSC und UC patients indicated that UC in PSC is a separate disease entity from primary UC, but expression studies for PSC are lacking. In this study, we performed a molecular comparison of whole blood expression levels in PSC only, PSC patients with additional UC diagnosis (PSC/UC), and UC, using a large collection of whole blood transcriptome data. Methods: We conducted whole blood RNA-Seq experiments for 495 UC patients, 220 PSC patients (of whom 177 have also a UC diagnosis), and 320 healthy controls from Germany and Norway. Differential expression analyses, gene ontology and coexpression analyses and random forest machine learning were performed to identify genes, ontologies and transcriptional features that discriminate diagnoses. Results: The blood transcriptome in UC and PSC is dominated by neutrophil activation genes. In UC, but not in PSC (neither PSC alone nor PSC/UC), there is upregulation of genes for ribosomes, mitochondria and energy metabolism genes in conjunction with antibody transcript expression. In PSC, there is an increase in modules related to apoptosis and expression of genes of interferon-I-related ontologies. Random forest analysis could poorly discriminate PSC alone from PSC/UC (AUROC 0.56), but could discriminate PSC, UC, and controls with high accuracy (AUROC UC vs controls 0.95, PSC vs controls 0.88, UC vs PSC 0.986). The main coexpression modules are enriched in neutrophil degranulation and antibody production genes relevant for distinguishing PSC, UC, and controls. Conclusions: PSC and UC share neutrophil-related transcriptional upregulation in whole blood (e.g. S100A12). UC is characterised by upregulation of modules involved in antibody production (MZB1, IGJ) and increased metabolic activity (PDK4, ribosomal genes), while PSC differs from UC by interferon (IFIT1) and apoptosis upregulation (G0S2). Supported by machine learning results, PSC and UC are interpreted as molecularly separate entities, while PSC/UC and PSC are indistinguishable.

Dataset Information

Interference with the lower gut-liver axis induces remission of primary sclerosing cholangitis in a patient with ulcerative colitis.

Publications

Interference with the lower gut-liver axis induces remission of primary sclerosing cholangitis in a patient with ulcerative colitis.

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