Hepatic encephalopathy: oral fecal microbiota transplant shows good tolerability

Vignette

A phase 1 clinical trial showed that oral fecal microbiota capsules were well tolerated by patients with cirrhosis and prone to developing hepatic encephalopathy.

 

Hepatic encephalopathy (HE) is a complication of liver failure and symptoms include more or less severe, sometimes irreversible, cognitive disorders. This disorder is related to a dysregulation of the gut-liver-brain axis as gut dysbiosis is observed in cases of HE and promotes systemic inflammation. Current treatments, which combine prebiotics (lactulose) and antibiotics (rifaximin) have proven to be inefficient in some patients. That is why, an American team is trying to develop alternative strategies.

Enema vs. oral administration

In 2017, the same team had tested fecal microbiota transplant performed by enema and concluded that it had beneficial effects: decrease in the number of HE episodes, associated to an improvement in cognitive functions and gut microbiota composition. In a new Phase-1 clinical trial, the team evaluated the tolerability and effects of FMT given through a less invasive and eagerly awaited administration route, i.e. capsules. In a blind trial, 20 patients with cirrhosis and history of HE (at least 2 episodes in the previous year) were randomized between the case group and the control group and were given 15 FMT capsules (from the same donor) or placebo. Afterwards, they were monitored for a period of 5 months.

Well tolerated treatment

What were the results? FMT capsules proved to be well tolerated by patients, with no adverse events. The number of HE episodes, as well as the number of infections occurred during the study were the same in both groups. However, an improvement in the score obtained in one cognitive test (out of two performed tests) was observed in patients from the FMT group.

Microbiota: towards a return to balance

An increase in microbiota diversity in the duodenal mucosa was also brought to light in the FMT group, as well as an increase in Ruminococcaceae and Bifidobacteriaceae populations and a decrease in Streptococcaceae and Veillonellaceae populations. The two latter families are associated to cirrhosis while the former two are rather beneficial. Moreover, this improvement of the microbiota is correlated to an increased expression of proteins involved in the function of the gut barrier and of AMO (antimicrobial peptide), as well as a decrease in two inflammation markers: IL-6 expression in the duodenum and LBP (Lipopolysaccharide Binding Protein) blood levels. This potential therapeutic avenue still needs to be confirmed.

 

Sources: 

Bajaj JS, Salzman NH, Acharya C et al. Fecal Microbial Transplant Capsules are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial. Hepatology. 2019 Apr 30. doi: 10.1002/hep.30690.