FMT shows promise in restoring gut barrier function, immunity in cirrhosis
Click Here to Manage Email Alerts
Fecal microbiota transplantation improved gut barrier function, mucosal immunity and ammonia metabolism in patients with cirrhosis, which could reduce hepatic encephalopathy and other infections, according to data from the PROFIT trial.
“Patients with cirrhosis have enteric dysbiosis,” Lindsey A. Edwards, BSC, MSc, PhD, research director of fecal microbiota transplant program at the Institute of Liver Studies at King’s College London, said during EASL Congress. “This means they lose beneficial [gut] species and they have enhanced pathogens. These cause damage and you get a leaky gut. Then, those microbes translocate across the gut and their microbial products. This chronic stimulation of your immune system means that you have a dysregulated immune response to infection.”
She continued: “Cirrhosis patients are really susceptible to infection, and this can lead to multiorgan failure and sadly death. Because of this chronic stimulation they have immune paralysis, so they are not able to kill and tackle those infections. We aimed to tackle this by doing fecal microbiota transplantation. We wanted to see if we could stop translocation across by improving barrier function and restoring host immunity.”
In the placebo-controlled, randomized, single-blinded feasibility PROFIT trial, Edwards and colleagues assessed the use of FMT in 32 patients (mean age, 57.1 years; mean MELD score, 13.1) with advanced cirrhosis. Patients were administered 50 grams of liquid frozen FMT (n = 15) or placebo (n = 6) into the jejunum via endoscopy.
At baseline and 7, 30 and 90 days after FMT or placebo administration, researchers collected blood, saliva, stool and urine samples to assess the efficacy of FMT in modulating a patient’s microbiome and inflammatory status, as well as fecal and plasma cytokine production and barrier integrity markers, metabolomics and fecal proteomics.
Using deep metagenomic sequencing, researchers confirmed FMT increased fecal microbial richness with donor engraftment. They also reported reduced biomarkers of inflammation and enhanced antimicrobial response and barrier function, including lactic acid and fermenting bacteria. A donor diet high in fiber and protein improved clinical outcomes.
“What we are doing with FMT is resetting those host responses to pathogens, but reducing inflammation and damage to the barrier,” Edwards said.
Researchers also identified 301 proteins via fecal proteomics, of which 154 were of human origin and 147 were bacterial.
FMT also significantly decreased plasma ammonia at 30 days (P = .0006). Compared with placebo, fecal ammonia was higher in patients administered FMT at both days 30 and 90.
“We reduced pathogens that produce ammonia in the blood and sure enough, we actually see a reduction in plasma ammonia after FMT and an increase in fecal ammonia,” Edwards said. “We are excreting out that ammonia and that actually correlates with a reduction in hepatic encephalopathy grade.”
In addition, researchers reported that FMT may reduce antibiotic-resistant infections and the need for antibiotics.
“By changing these species, what we are doing is enriching the enzymes that can metabolize and this is giving us the energy to restore the gut barrier and the energy to fight infection and promote colonization of the microbiome,” Edwards said. “We are enhancing metabolic reprogramming and intestinal barrier function and enhancing responses to infection.”
She added: “[FMT] shows great promise for modifying hepatic encephalopathy, deadly infections and possibly tackling antimicrobial resistance.”
Collapse
Edwards LA, et al. Abstract GS-007: Fecal microbiota transplant restores gut barrier function and augments ammonia metabolism in patients with advanced cirrhosis: a randomized single-blind placebo-controlled trial. Presented at: EASL Congress; June 21-24, 2023; Vienna (hybrid meeting).
Read more about
Click Here to Manage Email Alerts