Fecal Matter Transplant Shows Promise in Cirrhosis

VIENNA — Fecal microbiota transplants (FMT) helped reset gut microbiota, leading to strengthened gut barrier function and mucosal immunity in patients with cirrhosis, according to a U.K. trial.

For this pilot study called PROFIT, 50 grams of liquid frozen fecal microbiota was transplanted into the jejunum via endoscopy in 22 patients while another 10 patients were given placebo, explained Lindsey Edwards, PhD, of King’s College London at the European Association for the Study of the Liver (EASL) annual meeting.

She reported that enzymes required for nitrogen assimilation and excretion via the urea cycle were enhanced, with enhanced secretion of urinary hippurate (P=0.0299) at day 30 with FMT versus placebo.

FMT also improved ammonia metabolism, resulting in a reduction at 30 days in plasma ammonia (P=0.0006) versus placebo, while fecal ammonia was higher at 30 (P=0.011) and 90 days with FMT versus placebo (P=0.025).

Edwards cautioned that engraftment occurred at different amounts in the individual patients, and that FMT’s effects waned at 90 days. “We think we may have to re-treat patients after 90 days,” she said in response to an EASL attendee question. The researchers are moving ahead with a larger trial (PROMISE) that will recruit several hundred patients.

Edwards explained at an EASL press conference that patients with cirrhosis have reduced gut bacterial diversity with an overabundance of pathobionts in the gut microbiome. This imbalance, combined with compromised gut barrier function, allows bacteria to translocate the body and triggers a reduced antimicrobial immune response, which heightens the risk of infection and mortality.

EASL secretary general Thomas Berg, MD, of Leipzig University Medical Center in Germany, commented that “this exciting study confirms the growing awareness in recent times of the link between gut health and liver disease, and suggests that modulating the microbiome and restoring crucial functions holds tremendous potential for improving patient outcomes.”

Berg, who was not involved in the study, added that the findings “will be key to our scientific understanding around liver health for years to come.”

Aleksander Krag, MD, PhD, MBA, of Odense University Hospital in Denmark, told MedPage Today that he was not “surprised that transplanting this material in the gut could have an impact on the liver. If you look who is the closest friend of the gut, that’s the liver, anatomically and physiologically. All the blood and metabolites in the gut flow into the liver through the portal vein.”

“That’s also why we believe, and there’s a lot of data suggesting, that the relation between those in the gut impact what’s going on there in the liver,” said Krag, who was not involved in the study. “If the gut is sending bad signals to the liver, cirrhosis will progress. If you can change that environment, you may be able to remove some of the drivers of progression of cirrhosis.” He added that a healthy liver responds to the needs of the gut by sending out things like bile to aid in digestion.

The 32 PROFIT patients had advanced but stable cirrhosis, with a Model for End-Stage Liver Disease score 10-16. Edwards and colleagues assessed efficacy in modulating the patient’s own microbiome and inflammatory status, with blood and stool collected at baseline and days 7, 30, and 90 post-transplant or placebo. Cytokine production, markers of barrier integrity, global metabolite profile, and fecal proteomics also were evaluated.

They reported that deep metagenomic sequencing confirmed FMT boosted recipient species richness with significant donor engraftment. Also, FMT significantly cut stool carriage of Enterococcus faecalis and other pathobionts.

Edwards told MedPage Today that they are looking for “super donors” of fecal matter, explaining that “may be from someone who has an omnivorous diet. So you need some complex carbohydrates and you do need some protein.” She said that pilot studies often rely on donors who follow vegan or vegetarian diets.

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