Gut bacteria give accurate diagnosis of liver cirrhosis
4 August 2014
Scientists from the French National Institute for Agricultural
Research (INRA) in collaboration with a Chinese team found that the
gut microbiota of individuals with liver cirrhosis differ notably
from healthy individuals and have a high proportion bacteria common
in the mouth.
This discovery, published in the journal Nature ,
allowed researchers to build a non-invasive test for liver
cirrhosis, accurate to over 90%, based on the bacteria found in
patients' guts. This scientific breakthrough could have applications
for other chronic diseases and represents an important step in the
research for therapies.
Liver cirrhosis is a worldwide prevalent disease. Its main causes
are obesity, viral infections (hepatitis) and alcohol. It can lead
to cancer, or liver failure, requiring transplantation. It is
diagnosed mainly by a liver biopsy, an invasive method, which
requires hospitalization and is often contraindicated.
Specific bacterial communities
Scientists from INRA in Jouy-en-Josas and a Chinese team analyzed
the microbiome (collective genome of gut bacteria) of 250 liver
cirrhosis patients. By comparing the 2.7 million genes they found in
these individuals with previously established gene catalogues,
researchers identified 800,000 genes previously unknown. Refining
their analyses, they determined that 75,000 genes were very
differently spread between cirrhotic patients and healthy ones. In
terms of bacterial populations, 28 species were more abundant in
cirrhotic patients, against 38 species in healthy individuals.
Mouth bacteria in the gut
In cirrhotic patients, researchers found that up to 40% of the
intestinal microbiota can be comprised of bacteria that are rare in
healthy people; a majority of them were actually usual residents of
the mouth. S. Dusko Ehrlich, who led the study at INRA, comments: “A
possible explanation is that a deficiency of bile synthesis in liver
cirrhosis allows an invasion of the gut by the mouth bacteria”.
A reliable non-invasive diagnosis
Scientists created a simple test, based on stool analysis, to
identify liver cirrhosis patients by the abundance of only 7
bacterial species. This diagnostic tool is promising since it is
non-invasive and highly accurate (over 90%). Moreover, results show
a correlation between the proportion of the gut invaders and the
severity of the disease. S. Dusko Ehrlich said, “It could be
possible to not only diagnose liver cirrhosis but also determine the
stage of its advancement”.
Similar microbiota in Chinese and Europeans
As the study was based on a Chinese cohort, scientists also
sought to test whether Chinese intestinal microbiota were similar to
Europeans’. Thanks to bacterial gene catalogs, they confirmed that
healthy Chinese and Europeans harbor microbiota that were largely
similar, albeit not identical. Further analyses are needed to
confirm that alterations are also similar in liver cirrhosis
patients from both populations.
Future studies will be needed to understand the role of the
bacteria invading the gut of patients in liver cirrhosis.
Preliminary observations indicate that certain bacteria overproduce
molecules that are implicated in hepatic encephalopathy, a common
complication of liver cirrhosis. A therapeutic strategy would be to
inhibit these bacteria; another could target the malfunction of the
bile in order to prevent the migration from the mouth to the gut.
The novel findings on gut bacteria changes in liver cirrhosis
could provide useful leads for other chronic diseases. Oral bacteria
have already been observed to be more abundant in patients with
colorectal cancer or with Crohn’s disease than in healthy
individuals. Controlling and fighting this invasion of the gut from
the mouth could prove helpful in treating these serious diseases.
Nan Qin, et al. Human gut microbiome alterations in
liver cirrhosis. Nature, 23 July 2014. DOI : 10.1038/nature13568