Gut bacteria hint at silent liver disease

Researchers at Imperial College London have found a new way of potentially diagnosing fatty liver disease, using a molecule produced by the bacteria that colonise the human gut...

Fatty liver disease, a condition in which the liver is damaged due to accumulation of fat in its cells, is a growing problem. It is very closely linked to the current obesity epidemic, as the lifestyle factors that produce obesity, such as eating poorly and exercising little, also contribute to the development of fatty liver disease.

Up to a third of adults are estimated to have this condition - but notoriously, it doesn’t usually produce any symptoms until the liver is severely damaged. This is particularly unfortunate, as in its early stages, the disease is reversible. However, if it is caught too late, there is little that can be done about it, with the exception of a liver transplant. Additionally, the only way currently available for diagnosing fatty liver is a biopsy, a procedure in which a small part of the liver is taken using a needle. This can be uncomfortable, and is time-consuming. For these reasons, finding a quick and easy method to diagnose fatty liver disease in its early stages could be life-saving.

This particular study, led by Lesley Hoyles, examined the link between fatty liver disease and the ‘microbiome’, the collection of micro-organisms that live in and on the human body. Specifically, the team looked at the bacteria that colonise the gut. “It’s been noted that there are changes in the composition of the gut bacteria in diseased animals compared with healthy ones. Diseased animals have significantly fewer of the bacteria that we consider beneficial, and the functions that these bacteria carry out in the body are also reduced, but this has not really been looked at in humans” says Hoyles. “We particuarly targeted obese patients, because we know the microbiota are different between non-obese and obese individuals. We were looking at early stages of the disease to see whether or not we could identify biomarkers, or predictors, of whether people had fatty liver disease”, Hoyles says.

As part of the study, the team was looking at the metabolites the bacteria produced: “Metabolites are basically chemicals that gut bugs produce from the food we eat. They can be found in the blood, or can be excreted in the urine,” Hoyles explains. One particular metabolite, called phenylacetic acid, or PAA, was found to be strongly correlated with the level of liver damage: people with mild liver disease only had low levels of PAA in their blood, but those whose illness was more advanced showed higher levels. Interestingly, when human liver cells were treated with PAA in the lab, they developed features of fatty liver disease. Additionally, mice who were fed PAA also developed the condition. Hoyles thinks this is important in terms of our understanding of how the disease develops: “While we’re not saying the microbiome is necessarily causing fatty liver disease, it is certainly contributing to it.”

Aside from being of scientific interest, PAA could also have value in diagnosing fatty liver: “Potentially, we now have a biomarker for the disease,” says Hoyles. “We are hoping the phenylacetic acid levels could be used as an indicator of whether someone needs further tests to see if they have this condition.”

In this way, it might be possible to catch fatty liver disease much earlier, in the stages at which it is fully reversible. “We would give these people the same kind of advice that we would give to people who are diabetic for example: Eat more healthily, take more exercise, look after yourself a little bit better.”