The link between diabetes, obesity and NAFLD – where the liver is engorged with fat – is well known. What isn’t understood is why a relatively small but significant number of people with NAFLD end up with cirrhosis or scarring of the liver, which increases the risk of liver cancer.
Currently, for those with advanced fibrosis or scarring, transplants are often the only viable option. This is far from an ideal solution, though, especially given that diabetes and obesity – the primary causes of NAFLD – often preclude transplant surgery.
Liver and hepatology specialist Leon Adams, and his collaborators, are on a mission to get to the root of the problem and find a better solution.
“I’m interested in figuring out why, of all the people that have fatty liver disease, some people develop oppressive scarring or fibrosis and liver injury, which leads to cirrhosis and its complications,” said Dr Adams.
The first phase of Dr Adams’ research project focused on the influence of the gut microbiome – the bacteria within your gut.
“We know the gut microbiome is a lot more diverse than we originally thought,” said Dr Adams. “We also know that people who have fatty liver disease tend to have leaky guts, so they’re more prone to potentially damaging bacteria penetrating the gut wall, entering the blood stream and then the liver."
Our hypothesis is these bacterial products cause fibrosis or scarring of the liver. We know the gut microbiome is a lot more diverse than we originally thought.
To test the hypothesis, the research team recruited patients (including Barbara Sheridan, featured opposite) undergoing a liver biopsy as part of their clinical care or treatment. The patients also provided a faecal specimen.
“We looked at their liver biopsy, analysed their faecal samples and found that the patients with advanced fibrosis had a less diverse gut microbiome, meaning there are fewer different species of bacteria in the gut. We think this is because some pathogenic species are dominating the gut environment, upsetting the normal harmonious balance of good and bad bacteria,” said Dr Adams.
“It also seems that the bacteria that reside in the guts of people that have advanced fibrosis are the kind of bacteria that invade through the gut bacterial wall, which is in keeping with our hypothesis.”
The next phase of Dr Adams’ research is focused on finding a dietary intervention, although recent studies have shown that achieving lasting changes in microbiome through diet is incredibly hard.
“We’ve already conducted a diet study with people with fatty liver disease, comparing a Mediterranean diet with a low-fat diet, which we found to be equally effective,” he said. “Now, we’re looking at the microbiome changes to see if they mirror the improvement we see, to determine how changing your diet can change your microbiome and change your liver fat.”
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