Gut bacteria changes may provide strong evidence for early-stage liver disease
The research team think the production of phenylacetic acid (PAA) by gut microbes are a reliable indicator of the early onset of Non-Alcoholic Fatty Liver Disease (NAFLD).
By using PAA as a biological marker, a test could be devised in which blood from a patient could be screened for the compound that also flags up those at an increased risk of the condition.
“Through this work we may have uncovered a biomarker for the disease itself,” explained Dr Lesley Hoyles, lead study researcher from the Department of Surgery & Cancer at Imperial College, London.
“Overall, it demonstrates the microbiome is definitely having an effect on our health.”
So far, studies using rodents have highlighted the role of the gut microbiome in liver disease. NAFLD in particular shares a mode of action with other conditions like type 2 diabetes and cardiovascular disorders linking their development and range of symptoms.
Despite this, the physiological mechanisms behind this interplay remain poorly understood.
While NAFLD can be detected via a blood test and ultrasound scan, it may not be confirmed until there is significant liver damage.
Along with colleagues from INSERM in Toulouse and the Universities of Girona and Rome Tor Vergata, Dr Hoyles, examined the blood and urine, liver biopsies and faecal samples taken from 100 obese women with fatty livers.
The data was then compared to healthy patients in order to identify tiny variations between the two sample groups.
One notable variance was the increased production of PAA, a compound produced by the gut microbiome in larger quantities in the obese sample group.
Further inspection also revealed an association between afflicted with fatty liver disease and the minute changes in the microbiome’s profile.
The team suggested that the more advanced the disease, the more the total number of genes encoded by gut bacteria began to decrease, an indirect measure that the microbiome was less diverse – made up of fewer different types of bacteria.
“The scientific literature shows that the microbiome changes in a range of diseases. But it may be a case of ‘chicken and egg’, and not necessarily cause and effect,” said Dr Hoyles.
“It’s clear that the microbiome influences us because at any one time we have around 200 metabolites in our circulation from our gut bacteria, so they have long term effects and may be influencing disease.”
To further explore this line of investigation, the team treating healthy mice with PAA found it caused the build-up of fat in the liver.
Faecal transplants were also used in the research with mice developing fatty livers when transferring a faecal sample—along with its microbiome –from a patient with fatty liver disease.
“The collapse in genetic diversity of the gut bacteria observed in metabolic disorders is worrying,” said Imperial College’s Dr Marc-Emmanuel Dumas, from the university’s department of surgery & cancer and senior author on the study.
“Our gut microbes seem to lose the ability to make beneficial compounds and instead they start producing the ones setting us on a disease track.”
Dr Dumas believed the use of chemical signals produced by gut bacteria to spot disease was “exciting” though the prospect of a simple screening test at a GP clinic could be a number of years away.
He added, “We now need to explore this link further and to see if compounds like PAA can indeed be used to identify patients at risk and even predict the course of disease.
“The good news is that by manipulating gut bacteria, we may be able to prevent fatty liver disease and its long-term cardiometabolic complications.”
Source: Nature Medicine
Published online ahead of print: doi.org/10.1038/s41591-018-0061-3
“Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women.”
Authors: Lesley Hoyles et al.