» Articles » PMID: 36504550

Role of Intestinal Flora in Primary Sclerosing Cholangitis and Its Potential Therapeutic Value

Overview
Specialty Gastroenterology
Date 2022 Dec 12
PMID 36504550
Authors
Affiliations
Soon will be listed here.
Abstract

Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.

Citing Articles

The causal impact of genetically predicted inflammatory bowel disease on extraintestinal manifestations: a mendelian randomization study.

Fan X, He A, Li K, Zhang M, Zhang Q, Xiao W BMC Gastroenterol. 2025; 25(1):135.

PMID: 40038580 PMC: 11881308. DOI: 10.1186/s12876-024-03566-4.


Genetically predicted immune cells mediate the association between gut microbiota and autoimmune liver diseases.

Zhang J, Hu Y, Xu J, Shao H, Zhu Q, Si H Front Microbiol. 2024; 15:1442506.

PMID: 39736991 PMC: 11684339. DOI: 10.3389/fmicb.2024.1442506.


The Many Faces of Metabolic Dysfunction-Associated Fatty Liver Disease Treatment: From the Mediterranean Diet to Fecal Microbiota Transplantation.

Abenavoli L, Gambardella M, Scarlata G, Lenci I, Baiocchi L, Luzza F Medicina (Kaunas). 2024; 60(4).

PMID: 38674209 PMC: 11051743. DOI: 10.3390/medicina60040563.


Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model.

Hua H, Zhao Q, Kalagbor M, Yu G, Liu M, Bian Z World J Gastroenterol. 2024; 30(5):471-484.

PMID: 38414587 PMC: 10895596. DOI: 10.3748/wjg.v30.i5.471.


Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?.

Yang Y, He X, Rojas M, Leung P, Gao L Front Immunol. 2023; 14:1184252.

PMID: 37325634 PMC: 10266968. DOI: 10.3389/fimmu.2023.1184252.


References
1.
Sabino J, Vieira-Silva S, Machiels K, Joossens M, Falony G, Ballet V . Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD. Gut. 2016; 65(10):1681-9. PMC: 5036217. DOI: 10.1136/gutjnl-2015-311004. View

2.
Abarbanel D, Seki S, Davies Y, Marlen N, Benavides J, Cox K . Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol. 2012; 33(2):397-406. PMC: 3565076. DOI: 10.1007/s10875-012-9801-1. View

3.
Visseren T, Fuhler G, Erler N, Nossent Y, Metselaar H, IJzermans J . Recurrence of primary sclerosing cholangitis after liver transplantation is associated with specific changes in the gut microbiome pretransplant - a pilot study. Transpl Int. 2021; 33(11):1424-1436. PMC: 7689804. DOI: 10.1111/tri.13692. View

4.
Kummen M, Thingholm L, Ruhlemann M, Holm K, Hansen S, Moitinho-Silva L . Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis. Gastroenterology. 2021; 160(5):1784-1798.e0. PMC: 7611822. DOI: 10.1053/j.gastro.2020.12.058. View

5.
Horackova S, Plockova M, Demnerova K . Importance of microbial defence systems to bile salts and mechanisms of serum cholesterol reduction. Biotechnol Adv. 2017; 36(3):682-690. DOI: 10.1016/j.biotechadv.2017.12.005. View