What is the role of fecal microbiota transplantation (FMT) in the treatment of Primary Sclerosing Cholangitis (PSC)?

From the Guidelines

Fecal microbiota transplantation (FMT) for primary sclerosing cholangitis (PSC) is currently considered experimental and is not yet recommended as a standard treatment. While early research shows some promise, there are no approved FMT protocols for PSC patients outside of clinical trials. Some small studies have demonstrated improvements in liver biochemistry and microbiome composition following FMT in PSC patients, but these effects appear to be temporary, typically lasting only 3-6 months. The theoretical basis for using FMT in PSC stems from the gut-liver axis concept, where intestinal dysbiosis may contribute to PSC pathogenesis by promoting inflammation and bile duct damage.

Key Considerations

• Patients interested in FMT for PSC should seek enrollment in clinical trials rather than pursuing this as an off-label treatment.
• Important considerations include donor screening for pathogens, administration route (typically via colonoscopy or nasogastric tube), and potential risks including infection transmission and gastrointestinal side effects.
• Conventional PSC management with ursodeoxycholic acid and management of complications remains the standard of care, as stated in the guidelines by 1 and 1.
• The use of FMT in PSC is still being explored, and its potential benefits and risks are being investigated, as mentioned in the study by 1.

Current State of Research

• The most recent and highest quality study on the topic is from 2019, which suggests that FMT may be a promising approach in the treatment of PSC, but more research is needed to establish its safety and efficacy, as stated in the study by 1.
• The study by 1 highlights the need for further research in the field of PSC, including the exploration of the gut microbiome and its interactions with liver and biliary physiology.
• The guidelines by 1 emphasize the importance of a multidisciplinary approach in the management of PSC patients, and the need for further research to establish the role of FMT in the treatment of PSC.

Recommendations

• Patients with PSC should be managed with conventional treatment, including ursodeoxycholic acid and management of complications, until larger randomized controlled trials establish the safety and efficacy of FMT.
• Patients interested in FMT should seek enrollment in clinical trials to contribute to the ongoing research and to potentially benefit from this experimental treatment.
• Further research is needed to establish the role of FMT in the treatment of PSC, and to investigate its potential benefits and risks, as stated in the study by 1 and the guidelines by 1 and 1.

From the Research

Role of Fecal Microbiota Transplantation (FMT) in Primary Sclerosing Cholangitis (PSC)

• FMT has been proposed as a potential treatment for PSC, with several studies demonstrating its safety and potential benefits in improving liver enzyme profiles and gut microbiota diversity 2, 3.
• A phase IIa randomized placebo-controlled trial (FARGO) is currently underway to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD 2.
• The trial aims to determine the effect of FMT on serum alkaline phosphatase values over time, as well as its impact on other liver biochemical parameters, PSC risk scores, and health-related quality of life measures 2.
• Emerging evidence suggests that the gut microbiome plays a crucial role in the pathogenesis of PSC, with several studies demonstrating a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC 4, 5.
• FMT has been shown to increase bacterial diversity and engraftment in patients with PSC, which may correlate with improved liver enzyme profiles and clinical outcomes 3.
• While the current evidence is promising, further studies are needed to fully understand the role of FMT in the treatment of PSC and to determine its potential as a therapeutic strategy for this condition 6, 5.

Key Findings

• FMT is safe and potentially beneficial in improving liver enzyme profiles and gut microbiota diversity in patients with PSC 2, 3.
• The gut microbiome plays a crucial role in the pathogenesis of PSC, and FMT may be a useful therapeutic strategy for modifying the microbiome and improving clinical outcomes 4, 5.
• Further studies are needed to fully understand the role of FMT in the treatment of PSC and to determine its potential as a therapeutic strategy for this condition 6, 5.

Ongoing Research

• The FARGO trial is currently underway to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD 2.
• Further research is needed to fully understand the role of the gut microbiome in the pathogenesis of PSC and to determine the potential of FMT as a therapeutic strategy for this condition 4, 6, 5.