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FMT Safe for Patients With PSC, may Lower ALP
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Fecal microbiota transplantation in patients with primary sclerosing cholangitis was safe and may improve alkaline phosphatase levels, according to a study from The American Journal of Gastroenterology.
“It has been postulated that bacteria may stimulate an aberrant immune response resulting in the perpetuation of the biliary inflammation seen in PSC,” Jessica R. Allegretti, MD, MPH, from the Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues wrote. “Restoration of the microbiome is a reasonable target for therapy in PSC because there is no treatment, given the complexity of PSC-[inflammatory bowel disease] and the known interactions between genes, mucosal immunity, immune cell tracking, and the microbiome.”
Allegretti and colleagues enrolled 10 patients with PSC who underwent a single FMT from a single donor. Mean ALP at baseline was 489 U/L. Nine patients had concurrent ulcerative colitis and one patient had Crohn’s colitis.
Regarding the primary safety outcome, no patients experienced adverse events or serious adverse events related to treatment. One patient experienced sinusitis that the researchers determined was unrelated to treatment.
Three of the 10 patients experienced a 50% or more decrease in ALP levels during follow-up and seven patients experienced a 30% decrease in alanine aminotransferase levels, aspartate aminotransferase levels, or both.
Microbiota diversity and similarity to the donor increased in all patients post-FMT, with significant changes by week 1 (P .01) and an upward trend maintained through week 24.
The researchers also noted that the abundance of frequently engrafting operational taxonomic units post-FMT often correlated with decreased ALP levels. Operational taxonomic units associated with ALP improvement included the short-chain fatty acid-producing genera Odoribacter, Alistipes, and Erysipelotrichaceae incertae sedis.
“It has been reported that multiple FMTs are required to obtain remission in UC,” Allegretti and colleagues wrote. “Accordingly, we speculate that it may be possible to observe a further decrease in ALP levels if multi-FMT dosing in patients with PSC is performed. This emphasizes the need for dose finding and dose regimen studies in this nascent field.” – by Talitha Bennett
Disclosure: Allegretti reports consulting for and receiving research support from Finch Therapeutics Group. Please see the full study for all other authors’ relevant financial disclosures.
Perspective
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Dawn M. Sears, MD
Fecal microbial transplant (FMT) is one of the most mysterious and exciting therapies in modern medicine. Every week, we are discovering more diseases and health states that have a specific gut microbiome signature. Scientists, physicians and industry are only at the tip of the iceberg in understand the role of the gut microbiome in underlying chronic disease state, but one observation is rising to the surface: a diversified microbiome is associated with health and healing.
Multiple trials are using FMT as a therapeutic agent in various chronic disease with promising results. The most studied area of FMT for inflammatory bowel diseases (IBD) disease consistently results in correction of dysbiosis and improvement and sometimes remission of disease. FMT has also been used in patients with chronic liver disease, specifically to treat underlying hepatic encephalopathy.
Primary sclerosing cholangitis (PSC) has no FDA approved treatments. A recent small study in adults found that oral vancomycin could result in remission of ulcerative colitis (UC) in patients with PSC. The current study involved performing a single FMT in patients with PSC and IBD with elevated alkaline phosphatase. The fact that bacterial diversity was achieved and maintained was expected. The outcome of 3/10 patients experienced a sustained significant decrease in their alkaline phosphatase is the exciting news. This simple biomarker for disease is not the ultimate goal of PSC therapy, however, patients with lower alkaline phosphatase levels do have superior outcomes and this is the first step in all PSC therapies investigated.
As the authors note, the next step will be consideration of upper GI delivery and possibly multiple dosages of FMT. This positive outcome may ultimately hit two birds with one stone and be cost-effective. The world of FMT and liver-gut-microbiome is in its toddlerhood and the future looks bright.
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