Faecal microbiota transplantation (FMT), which helps restore a healthy mix of bacteria
in the gut, can help reverse brain function impairment in people
with liver failure,
according to a report at the International Liver Congress last week in
Vienna.
FMT
capsules led to the restoration of bacterial diversity in the gut and
improvement of cognitive function in people with hepatic encephalopathy as a
consequence of advanced cirrhosis, Dr Jasmohan Bajaj of Virginia
Commonwealth University reported.
Over years or
decades, chronic hepatitis B or C, fatty liver disease, heavy alcohol
consumption and other causes of liver injury can lead to cirrhosis,
hepatocellular carcinoma and end-stage liver failure requiring a transplant.
Glossary
- ascites
An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
- encephalopathy
-
A disease or infection affecting the brain.
In people with
decompensated cirrhosis, the liver can no longer carry out its vital functions
due to the accumulation of scar tissue and blockage of blood flow.
Complications may include ascites (fluid build-up in the abdomen), bleeding
veins in the oesophagus and hepatic encephalopathy, which occurs when the liver
can no longer filter out ammonia and other toxins.
Symptoms of hepatic
encephalopathy may include impaired cognition, poor concentration, confusion,
personality changes and coma. Over time, recurrent bouts of encephalopathy can
lead to lasting brain damage, according to Dr Bajaj. Treatments include
lactulose, a non-digestible sugar that absorbs ammonia and acts as a laxative,
and the non-absorbable antibiotic rifaximin.
Lactulose and
antibiotics can change the makeup of bacteria in the intestines, known as the
gut microbiome. Some types of gut bacteria produce ammonia, which worsens
encephalopathy, while others trigger systemic inflammation.
Studies have shown
that altering the gut microbiome can help prevent or improve hepatic
encephalopathy. For example, research presented
at the 2013 International Liver Congress showed that a probiotic supplement
reduced ammonia levels, improved cognitive function and prevented
encephalopathy progression in people with advanced liver disease.
Transplanting
gut bacteria from a healthy individual is another way to restore a beneficial
microbiome. FMT involves transferring donor faeces via an enema formulation or
oral capsules.
Dr Bajaj
and colleagues previously
showed that FMT via enema improved cognitive function and
reduced hospitalisations in people with advanced liver cirrhosis. They then
evaluated the safety, tolerability and effectiveness of a capsule formulation, which
is more convenient and can deliver beneficial bacteria to the small intestine,
not just the colon.
This phase
I study included 20 people with cirrhosis and recurrent hepatic encephalopathy
who were receiving lactulose and rifaximin. Participants were randomly assigned
to receive 15 FMT capsules or similar placebo capsules in addition to their
existing therapy.
The
capsules were prepared using stool from a single donor – the same so-called 'super
pooper' who donated for the enema FMT study – with high levels of beneficial Lachnospiraceae and Ruminococcaceae bacteria species. Dr Bajaj stressed that the
capsules "do not smell like poop and do not taste like poop."
At the start of the study, microbial
diversity in stool samples and biopsy samples from the small intestine
(duodenum) and large intestine (sigmoid colon) was similar in both groups. After
two to four week of treatment, however, people in the FMT group saw an increase
in bacterial diversity, with more Ruminococcaceae
and Bifidobacteriaceae bacteria and a
decrease in Streptococcaceae and Veillonellaceae species. Duodenum biopsy
samples also showed a reduction in biomarkers of inflammation.
Cognitive function scores using a
standardised assessment test improved in the FMT group compared with the
placebo group. Just one participant required hospitalisation or died in the FMT
group while six did so in the placebo group. The total number of hospitalisations
was also significantly lower in the FMT group. No safety issues were identified
during the study.
"Faecal microbiota transplant using a
single stool donor enriched with bacterial species we know are deficient in
this population is a promising approach to the potential treatment of patients
with cirrhosis and recurrent hepatic encephalopathy," Dr Bajaj said.
"The way to the brain is through the gut."