Oral Fecal Capsule Promising for Hepatic Encephalopathy

Ingrid Hein

April 19, 2019

VIENNA — For patients with cirrhosis who experience recurrent hepatic encephalopathy, an oral formulation of fecal microbiota is safe and effective, new research shows.

"This is an underserved population for whom we have nothing left to offer," said investigator Jasmohan Bajaj, MD, from the Virginia Commonwealth University Medical Center and the McGuire VA Medical Center in Richmond.

These "very sick" people "have inflammation in the liver, systemic inflammation, are experiencing low cognitive function, and are already on the maximum FDA-approved drugs," he explained.

In such patients, the composition and function of the gut microbiota are altered and the intestinal barrier is impaired, he said here at the International Liver Congress 2019. Fecal microbiota transplantation can repair that, which improves quality of life and disease symptoms.

In their study, Bajaj and his colleagues assessed the effect of fecal microbiota capsules from a single donor with high levels of Lachnospiraceae and Ruminococcaceae on patients with cirrhosis and recurrent hepatic encephalopathy (Hepatology. Published online April 30, 2019). On the same day, 10 study participants took 15 microbiota capsules and 10 took placebo capsules.

Participants were matched for age, sex, and race, and the investigators verified that microbial diversity in the stool, sigmoid, and duodenal mucosa was similar in the two groups at baseline (P > .05).

MELD scores were similar in the fecal and placebo groups at baseline (9.6 vs 10.2) and at the end of the 5-month study (10.2 vs 10.5).

With every recurrence of hepatic encephalopathy, these patients get "further into a dementia," Bajaj explained. "If their MELD score gets too low, there's no hope for a liver transplant."

The Right Fecal Donor Essential

The team found their ideal fecal donor through OpenBiome, a nonprofit stool bank. "We wanted a specific donor," with high levels of the "bugs missing in patients with hepatic encephalopathy," he said.

They chose the donor with the highest concentrations of Lachnospiraceae and Ruminococcaceae to create their fecal capsules.

Stool samples from the study participants were assessed with RNA sequencing every 30 days for 5 months to see if Lachnospiraceae and Ruminococcaceae were replenished.

In the microbiota group, there was a significant increase in duodenal mucosal microbial diversity at 5 months (P = .01), a relative abundance of Ruminococcaceae and Bifidobacteriaceae, and a decrease in Streptococcaceae and Veillonellaceae.

Improvement in cognitive function, assessed with the EncephalApp Stroop Test, was significantly better in the fecal group than in the placebo group (P = .02).

There were fewer serious adverse events that required hospitalization during follow-up in the fecal group than in the placebo group (1 vs 6; P = .05), and one patient in the placebo group died.

"We wanted to show safety and we got it," said Bajaj.

Reduction in Hospitalizations

Although making "crapsules" from a "super pooper" has been the object of ridicule, this is very serious medicine and the results are life-altering, he said.

"There was a significant reduction in hospitalizations" with the oral formulation, which conferred on these patients "a benefit to their microbiome throughout their GI tract," he reported.

The treatment significantly reduced lipopolysaccharide binding protein, which "produces a lot of the inflammation that starts from the gut, goes to the liver, and systemically affects the brain," he explained. "Reduction means that the intestinal barrier is stronger."

In addition, fecal microbiota transplantation increased antimicrobial peptides and proteins, which are essential proteins that kill bacteria, yeasts, fungi, viruses, and even cancer cells. "That helps protect the intestinal barrier against invaders," he pointed out.

And there was a significant reduction in interleukin-6, which has been implicated in intestinal inflammation (P = .02), he added.

"This is good sh**," Bajaj said.

Placebo Group Now Possible

Bajaj was involved in a similar study 2 years ago, as reported by Medscape Medical News, but the microbiota were delivered through an enema so there was no placebo group.

With the capsules, "we could hide the difference," he noted.

In the previous study, an antibiotic was administered before transplantation, which skewed the results. "We got a lot of criticism the last time. No placebo group and we gave antibiotics," he said.

Bajaj said he would like to conduct a study to compare microbiota capsules with enema-delivered microbiota.

How can you prepare a pill with standardized gut microbiota?

The capsule provides an easier delivery mechanism than colonoscopy. "This approach is really outstanding," said Gianluca Svegliati-Baroni, MD, from the Marche Polytechnic University in Ancona, Italy.

"It's revolutionary in my mind," he told Medscape Medical News. There are potentially millions of patients who can benefit from this treatment.

However, he asked, "How can you prepare a pill with standardized gut microbiota?"

The biggest problem with fecal microbiota transplantation is that there is a limited amount of stool from each donor. Plus, the donation, even if from the same person, is slightly different every time, depending on what they've eaten, he explained.

Hepatic encephalopathy is "difficult to treat," Svegliati-Baroni added. "Patients have a very low quality of life, and that interferes with the family's life."

"Microbiota are really an interesting aspect of treatment," he said.

Bajaj and Svegliati-Baroni disclosed no relevant financial relationships.

International Liver Congress (ILC) 2019. Abstract PS-087. Presented April 12, 2019.

Editor's note: This story was updated to reflect the fact that the study by Bajaj and his colleagues has now been published.

Follow Medscape Gastroenterology on Twitter @MedscapeGastroand Ingrid Hein @ingridhein

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