How gut bacteria may help to spot and address liver disease

Nonalcoholic fatty liver disease will often have no symptoms in its early stages, so it may remain undetected until it becomes much more difficult to treat or manage. But a compound released by our gut bacteria may aid early diagnosis, researchers say.

In nonalcoholic fatty liver disease (NAFLD), excess fat builds up in the liver, thereby inhibiting its normal functioning.

Certain people are more at risk of developing this condition, and this includes those with obesity, high blood pressure, and type 2 diabetes.

It is hard to diagnose NAFLD in its early stages, however, as it does not display many telling symptoms at first.

This might mean that the condition may remain "hidden" until it has reached a more advanced stage, causing liver damage.

For this reason, researchers have been looking for ways of detecting liver disease as it begins to develop, so that it can be addressed as soon as possible.

Specialists from Britain, Italy, Spain, and France now say that it may be possible to detect NAFLD early on by looking at certain gut biomarkers.

"We have discovered exciting connections between gut microbiota composition, fatty liver, and carbohydrate metabolism," explains Prof. José Manuel Fernández-Real, from the University of Girona in Spain.

"This contributes," he adds, "to better understand[ing] why 30 percent of [people] with massive obesity do not develop a fatty liver despite dramatically increased fat mass."

The team's findings have been published in the journal Nature Medicine.

A new biomarker for fatty liver

The researchers analyzed the relevant medical data of 100 women who had a diagnosis of obesity — but who were free of diabetes — and who also had NAFLD.

More specifically, the team looked at a series of samples collected from the participants, including samples of blood, urine, feces, and liver biopsies.

They compared these data with sets of corresponding data collected from healthy individuals, in order to identify any telling differences between the two sets.

A detailed analysis revealed that raised levels of a compound called phenylacetic acid (PAA), which is released by certain gut bacteria, was linked to the excess fat buildup in the liver and early onset of NAFLD.

This means that PAA could be considered as a NAFLD biomarker, and diagnosing this condition would therefore be just one simple blood test away.

"Through this work we may have uncovered a biomarker for the disease itself," notes study leader Dr. Lesley Hoyles, from Imperial College London in the United Kingdom. "Overall, it demonstrates the microbiome is definitely having an effect on our health."

But the scientists also found that NAFLD was associated with certain changes in the composition of the gut microbiome.

A case of 'chicken and egg?'

Interestingly, the researchers saw that as NAFLD advanced, the number of genes encoded by gut bacteria gradually decreased, suggesting that the microbiome became poorer and less diverse in its microbial makeup.

We already know that the number of active genes encoded by gut bacteria is approximately 500 times greater than the number of genes found in human DNA, but how this may affect our overall health and biological functioning still holds many mysteries.

Still, scientists believe that a less diverse gut microbiome may be an indicator of poorer health — people with metabolic diseases, for instance, have fewer active genes encoded by gut bacteria.

And now, the researchers involved in the current study have observed a similar association in the case of fatty liver disease, noting that a less diverse gut microbiome was linked to symptoms of metabolic problems. This includes liver inflammation and non-responsiveness to insulin, the hormone that is key to regulating blood sugar levels.

In looking at other studies involving animal models, the researchers found that increasing PAA levels in healthy mice caused fat buildup in the rodents' livers.

Moreover, effecting fecal transplants with samples taken from NAFLD patients to mice whose gut microbiomes had been wiped clean with antibiotics also led to fatty livers in the rodents.

All this evidence points to a strong link between a poorer gut microbiome with a modified bacterial population and the development of NAFLD. But despite this, it is unclear whether changes in the gut bacteria cause the disease, or vice versa.

"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."

Dr. Lesley Hoyles

Simpler screening methods on the horizon

Still, the researchers involved in the current study are excited about their findings and what new possibilities they may lead to, in terms of diagnostic procedures.

As senior author Dr. Marc-Emmanuel Dumas explains, "The concept that we could use chemical signals produced by our gut bacteria to spot disease is an exciting one."

"It opens the possibility that [a] simple screening test at a [...] clinic could one day be used to spot the early signs of disease," he adds.

He warns, however, that "these kinds of tests may still be a number of years away from the clinic."

The next step from here, explains the senior author, will be to refine our understanding of PAA and how it might be used as a diagnostic tool for fatty liver disease. He also hopes that, in the future, we may be able to prevent the development of NAFLD by targeting the gut microbiome.

"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," noted Dr. Dumas.

"The good news is that by manipulating gut bacteria, we may be able to prevent fatty liver disease and its long-term cardiometabolic complications," he concludes.