The “gut microbiota” hypothesis in primary sclerosing cholangitis

Pontecorvi, Valerio; Carbone, Marco; Invernizzi, Pietro

doi:10.21037/atm.2016.12.43

Cited by 10 publications

(9 citation statements)

References 14 publications

(15 reference statements)

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“…Gut microbiota is normally confined in the intestinal lumen and engages in reciprocal beneficial activities with the host during homeostasis. A functional imbalance in the microbial ecosystem favors epithelial barrier dysfunction and increased intestinal permeability, leading to the translocation of gut-derived products into the portal venous system, with consequent biliary inflammation and liver fibrosis [ 5 , 6 ]. Thus, the “gut-liver axis” has been implicated in the pathogenesis of liver diseases, such as PSC [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Indole-3-Carboxaldehyde Restores Gut Mucosal Integrity and Protects from Liver Fibrosis in Murine Sclerosing Cholangitis

D’Onofrio

Renga

Puccetti

et al. 2021

Cells

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Primary sclerosing cholangitis (PSC) is a long-term liver disease characterized by a progressive course of cholestasis with liver inflammation and fibrosis. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC. According to the “leaky gut” hypothesis, gut inflammation alters the permeability of the intestinal mucosa, with the translocation of gut-derived products that enter the enterohepatic circulation and cause hepatic inflammation. Thus, the administration of molecules that preserve epithelial barrier integrity would represent a promising therapeutic strategy. Indole-3-carboxaldehyde (3-IAld) is a microbial-derived product working at the interface between the host and the microbiota and is able to promote mucosal immune homeostasis in a variety of preclinical settings. Herein, by resorting to a murine model of PSC, we found that 3-IAld formulated for localized delivery in the gut alleviates hepatic inflammation and fibrosis by modulating the intestinal microbiota and activating the aryl hydrocarbon receptor-IL-22 axis to restore mucosal integrity. This study points to the therapeutic potential of 3-IAld in liver pathology.

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Section: Introductionmentioning

confidence: 99%

Indole-3-Carboxaldehyde Restores Gut Mucosal Integrity and Protects from Liver Fibrosis in Murine Sclerosing Cholangitis

D’Onofrio

Renga

Puccetti

et al. 2021

Cells

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“…However, current clinical studies on the relationship between IBD and PBC were limited, consisting mostly of case reports, including one in which a patient developed PBC after having a colectomy, implying that surgery may be a factor in promoting disease progression [31] . In addition, gut permeability disruption in IBD may result in bacterial translocation, subsequent activation of cholangiocytes via the portal system, and activation of in ammatory responses and brosis in the liver, ultimately leading to the development of PBC [32] .…”

Section: Discussionmentioning

confidence: 99%

Causal Associations Between Inflammatory Bowel Disease and Primary Biliary Cholangitis: A Two-Sample Bidirectional Mendelian Randomization Study

Zhao

Liao

2023

Preprint

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Background Inflammatory bowel disease (IBD) was reported to be associated with hepatobiliary disease. Previous observational and Mendelian randomization (MR) studies suggested a causal association between IBD and primary sclerosing cholangitis (PSC). However, it is unclear whether IBD has causal association with primary biliary cholangitis (PBC): another autoimmune liver disease. Methods We obtained genome-wide association study (GWAS) statistics from published GWASs for PBC, UC and CD. We screened qualified instrumental variables (IVs) based on the three major assumptions of MR. To determine the causal relationship between UC or CD and PBC, two-sample MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods, and sensitivity analyses were conducted to validate the robustness of the results. We also conducted reverse MR analysis to reveal the causal association between PBC and UC or CD. Results UC were associated with a higher risk of PBC (OR = 1.35, 95% CI: 1.05–1.73, P = 0.02) in IVW method. And CD was associated with an increased risk of PBC (OR = 1.18, 95% CI: 1.03–1.36, P = 0.02) in IVW method. The weighted median and MR-Egger regression of both diseases showed a consistent direction but not statistically significant. Results of reverse MR analysis did not suggest genetic susceptibility to psoriasis was associated with increased risk of UC (OR = 1.05, 95% CI: 0.95–1.17, P = 0.34) or CD (OR = 1.1, 95% CI: 0.99–1.20, P = 0.06). Conclusion The present study revealed that IBD subtypes could increase the incidence of PBC, but in turn PBC did not increase the incidence of IBD subtypes. Understanding that IBD and PBC constitute mutual risk factors can help with clinical management of both diseases.

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“…Another “leaky gut” hypothesis proposed to explain the disease process in PSC inspired us to investigate the pathogenesis of hepatobiliary disorders. The disruption of bowel permeability may lead to bacterial translocation and bile colonization and subsequently activate the inflammatory response and fibrosis in the liver by activating cholangiocytes[ 30 ]. A case report described a female patient with UC who developed PBC after proctocolectomy[ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis: A case report and review of the literature

Zhou¹,

Zhou²,

Sun³

et al. 2021

WJG

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BACKGROUND Autoimmune enteropathy (AIE) and primary biliary cholangitis (PBC) are both immune-mediated diseases. AIE or PBC complicated with ulcerative colitis (UC) are rare. There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before, and the pathogenesis of these comorbidities has not been revealed. CASE SUMMARY A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease, and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016. A few months after the neoileostomy, she began to suffer from recurrent episodes of watery diarrhea. She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect. However, her symptoms of diarrhea relapsed in 2019, with different histological features of endoscopic biopsies compared with 2016, which showed apoptotic bodies, a lack of goblet and Paneth cells, and villous blunting. A diagnosis of AIE was established, and the patient’s stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d. Meanwhile, her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC, and treatment with ursodeoxycholic acid (16 mg/kg per day) achieved satisfactory results. CONCLUSION Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients. Continuous follow-up is essential for UC patients with postoperative complications.

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The “gut microbiota” hypothesis in primary sclerosing cholangitis

Cited by 10 publications

References 14 publications

Indole-3-Carboxaldehyde Restores Gut Mucosal Integrity and Protects from Liver Fibrosis in Murine Sclerosing Cholangitis

Indole-3-Carboxaldehyde Restores Gut Mucosal Integrity and Protects from Liver Fibrosis in Murine Sclerosing Cholangitis

Causal Associations Between Inflammatory Bowel Disease and Primary Biliary Cholangitis: A Two-Sample Bidirectional Mendelian Randomization Study

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis: A case report and review of the literature

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