An invasion of the gut by mouth bacteria could be responsible
for the development of liver cirrhosis, according to new
research.
Professor Stanislav Dusko Ehrlich, Director of the new
Host-Microbiome Centre at King's College London's Dental Institute
worked with w research team from China and scientists from INRA in
France. They found that the gut microbiota of individuals with
liver cirrhosis differed notably from those found in healthy
individuals, showing a high proportion of oral bacteria.
The findings allowed researchers to build a non-invasive test
for liver cirrhosis that showed a diagnostic accuracy of over 90
per cent. The breakthrough could have applications for other
chronic diseases and represents an important step in the search for
novel treatments.
Bacteria and viruses in the body make up a diverse collection of
microbes known as the human microbiome. These are essential for
various human processes, such as digestion, but the unique
collection of microbes in an individual may influence
susceptibility to certain diseases. The mouth itself harbours one
of the most diverse microbiomes in the human body and the bacteria
present can lead to tooth decay and gum disease but can also be
protective.
Cirrhosis is scarring of the liver as a result of continuous,
long-term liver damage, often caused by obesity, viral infections
and alcohol. Around 4,000 people in the UK die from liver cirrhosis
each year. It is diagnosed mainly by liver biopsy, an invasive
method which requires the patient to be hospitalised.
The researchers analysed the microbiome of some 250 individuals,
half of whom had liver cirrhosis. By comparing the 2.7 million
genes they found in these individuals with previously established
gene catalogues, they identified 800,000 previously unknown genes.
Refining their analyses, the team 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, compared to 38 species in healthy
individuals.
In cirrhotic patients, researchers found that up to 40 per cent
of the intestinal microbiota can be comprised of bacteria that are
rare in healthy people. The majority of these usually reside in the
mouth.
Professor Ehrlich said: "A possible explanation is that a
deficiency of bile synthesis in liver cirrhosis allows an invasion
of the gut by the mouth bacteria."
The researchers also created a simple test, based on stool
analysis, to identify liver cirrhosis patients by the abundance of
only seven bacterial species. This diagnostic tool is promising
since it is non-invasive and has an accuracy level of over 90 per
cent. Moreover, results show a correlation between the proportion
of the gut invaders and the severity of the disease.
Professor Ehrlich added: "It could be possible to not only
diagnose liver cirrhosis but also determine the stage of its
advancement."
Future studies will be needed to understand the role of this
bacteria invasion in the development of liver cirrhosis. Early
findings suggest 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 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.
The paper, Alterations of the human gut microbiome in liver cirrhosis, is
published in Nature.