Also known as “fatty liver disease” or “soda disease”, non-alcoholic fatty liver disease (NAFLD) is a silent, symptom-free disease that insidiously degrades the liver. Involved: excessive consumption of sugar and fat, which can lead to liver failure and, eventually, cirrhosis or cancer.
While people suffering from obesity, high blood pressure or type 2 diabetes are more at risk of developing fatty liver disease, the fact remains that the diagnosis is very often established too late, when the liver damage are irreversible and require a transplant.
For several years, however, researchers have been trying to find ways to diagnose non-alcoholic fatty liver disease earlier so that it can be treated as quickly as possible. A European consortium (FLORINASH), bringing together French, Italian and English researchers, may have achieved this by collecting data from two cohorts of 800 men and women suffering from obesity, and separating them into groups based on the presence or absence of “fatty liver”.
The researchers then analyzed the medical data of 100 obese women with non-alcoholic fatty liver disease but no diabetes. Blood, urine, stool and liver biopsy samples were collected and compared with similar samples collected from healthy individuals. The detailed analysis of the data revealed the presence, in people with NASH, of high levels of a compound called phenylacetic acid. Released by some intestinal bacteria, it is thought to be due to the accumulation of excess fats in the liver and the early onset of hepatic steatosis.
“Thanks to this work, we may have discovered a biomarker for the disease itself,” says Dr. Lesley Hoyles, of Imperial College London, UK, to Nature Medicine. “Overall, it shows that the microbiota definitely has an effect on our health.” If phenylacetic acid is indeed a biomarker of hepatic steatosis, it gives hope for the development of an early diagnosis of this condition by a simple blood test.
Another discovery made by the researchers is that NASH could change the composition of the gut microbiota. When the disease is detected, the number of genes encoded by intestinal bacteria gradually decreases, suggesting that the microbiota becomes poorer and less diverse in its microbial composition. A less diverse microbiota can cause metabolic problems such as inflammation of the liver and non-response to insulin, the hormone that regulates blood sugar levels.
The scientific team now wishes to continue its research around the signals produced by the intestinal bacteria and which could, in the long term, make it possible to diagnose the diseases early. “This opens the possibility that a simple screening test in a clinic […] can one day be used to detect the first signs of the disease,” says Professor Marc-Emmanuel Dumas, researcher at Imperial College London.
However, it will be years before a screening test is clinically tested. To achieve this, researchers need to refine their understanding of phenylacetic acid and its role in the diagnosis of fatty liver disease. “We must now further explore this link and see if phenylcetic acid compounds can actually be used to identify patients at risk and even predict the course of the disease,” says Professor Dumas.
The idea is also to be able to lead to the development of a new generation of probiotics and a pharmacological strategy interfering with the bacterial mechanisms responsible for liver disease. “The good news is that by manipulating intestinal bacteria, we may be able to prevent liver steatosis and its long-term cardiometabolic complications,” the researcher concludes.