Universal gut microbiome-derived signature predicts cirrhosis
June 30, 2020
Science Daily/University of California - San Diego
Researchers report that stool microbiomes of NAFLD patients are distinct enough to potentially be used to accurately predict which persons with NAFLD are at greatest risk for having cirrhosis.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide, affecting an estimated one-quarter of the global population. It is a progressive condition that, in worst cases, can lead to cirrhosis, liver cancer, liver failure and death.
In a new paper published online June 30, 2020 in Cell Metabolism, a team of scientists, led by researchers at University of California San Diego School of Medicine, report that stool microbiomes -- the collection of microorganisms found in fecal matter and in the gastrointestinal tract -- of NAFLD patients are distinct enough to potentially be used to accurately predict which persons with NAFLD are at greatest risk for having cirrhosis -- the late-stage, irreversible scarring of the liver that often requires eventual organ transplantation.
"The findings represent the possibility of creating an accurate, stool microbiome-based, non-invasive test to identify patients at greatest risk for cirrhosis," said senior author Rohit Loomba, MD, professor of medicine in the Division of Gastroenterology at UC San Diego School of Medicine and director of its NAFLD Research Center. "Such a diagnostic tool is urgently needed."
Loomba said a novel aspect of the study is the external validation of gut microbiome signatures of cirrhosis in participant cohorts from China and Italy. "This is one of the first studies to show such a robust external validation of a gut microbiome-based signature across ethnicities and geographically distinct cohorts.
The work builds upon previous published research in 2017 and 2019 by Loomba and colleagues.
A link between NAFLD and the gut microbiome is well-documented, but specifics were scant and it has not been clear that discrete metagenomics and metabolomics signatures might be used to detect and predict cirrhosis. In the latest study, researchers compared the stool microbiomes of 163 participants encompassing patients with NAFLD-cirrhosis, their first-degree relatives and control-patients without NAFLD.
Combining metagenomics signatures with participants' ages and serum albumin (an abundant blood protein produced in the liver) levels, the scientists were able to accurately distinguish cirrhosis in participants differing by cause of disease and geography.
The next step, said Loomba, is to establish causality of these gut microbial species or their metabolites in causing cirrhosis, and whether this test can be used and scaled up for clinical use.
https://www.sciencedaily.com/releases/2020/06/200630125126.htm
Green tea extract combined with exercise reduces fatty liver disease in mice
Although untested in human trials, results suggest a potential health strategy
February 14, 2020
Science Daily/Penn State
The combination of green tea extract and exercise reduced the severity of obesity-related fatty liver disease by 75% in mice fed a high-fat diet, according to researchers, whose recent study may point to a potential health strategy for people.
The outcome is important, explained Joshua Lambert, associate professor of food science, because nonalcoholic fatty liver disease is a significant global health problem that is expected to worsen. Because of the high prevalence of risk factors such as obesity and type 2 diabetes, fatty liver disease is forecast to afflict more than 100 million people by 2030. And there are currently no validated therapies for the disease.
In the study, mice fed a high-fat diet for 16 weeks that consumed green tea extract and exercised regularly by running on a wheel were found to have just a quarter of the lipid deposits in their livers compared to those seen in the livers of a control group of mice. Mice that were treated with green tea extract alone or exercise alone had roughly half as much fat in their livers as the control group.
In addition to analyzing the liver tissues of mice in the study, which was published recently in the Journal of Nutritional Biochemistry, researchers also measured the protein and fat content in their feces. They found that the mice that consumed green tea extract and exercised had higher fecal lipid and protein levels.
"By examining the livers of these mice after the study concluded and by screening their feces during the research, we saw that the mice that consumed green tea extract and exercised actually were processing nutrients differently -- their bodies were handling food differently," Lambert said.
"We think the polyphenols in green tea interact with digestive enzymes secreted in the small intestine and partially inhibit the breakdown of carbohydrates, fat and protein in food," he added. "So, if a mouse doesn't digest the fat in its diet, that fat and the calories associated with it pass through the mouse's digestive system, and a certain amount of it ends up coming out in its feces."
It may be significant, Lambert explained, that mice treated with both green tea extract and exercise had higher expression of genes related to the formation of new mitochondria. That gene expression is important, he said, because it provides markers that will help researchers understand the mechanism by which green tea polyphenols and exercise might work together to mitigate fatty liver deposits.
"We measured the expression of genes that we know are related to energy metabolism and play an important role in energy utilization," Lambert said. "In the mice that had the combination treatment, we saw an increase in the expression of genes that wasn't there before they consumed green tea extract and exercised."
More research is needed to see if there is a synergy created by green tea extract and exercise working together to reduce fat deposited in the liver, or if the effects are simply additive, Lambert pointed out. His research group in the College of Agricultural Sciences for 12 years has studied the health benefits of polyphenols -- often called antioxidants -- from green tea, cocoa, avocados and other sources.
In previous related research, Lambert and colleagues demonstrated that green tea extract and exercise together sharply reduced body mass and improved cardiovascular health of high-fat-fed mice. But because no human trials assessing the health benefits and risks of green tea combined with exercise have been conducted, he urges caution for people who decide to experiment with the health strategy on their own.
"I believe people should engage in more physical activity, and replacing high-calorie beverages with decaffeinated, diet green tea -- which has no calories -- is a smart move," he said. "Combining the two might have health benefits for people, but we don't have the clinical data yet."
https://www.sciencedaily.com/releases/2020/02/200214134655.htm
Obesity crisis blamed for a rise in fatty liver disease amongst young adults
January 15, 2020
Science Daily/University of Bristol
One in five young people have fatty liver disease (steatosis), with one in 40 having already developed liver scarring (fibrosis), research published today [15 January] has found. The study, published in The Lancet Gastroenterology & Hepatology, is the first to attempt to determine the prevalence of fatty liver disease and fibrosis in young healthy adults in the UK.
Fatty liver disease is a condition in which fats build up in the cells of the liver. It is broadly split into non-alcoholic fatty liver disease (NAFLD), which is usually seen in people who are overweight or obese, and alcohol related fatty liver disease, which is associated with harmful levels of drinking. If left untreated both can lead to fibrosis (scarring of the liver) and in severe cases eventually cirrhosis of the liver, which is irreversible. Worldwide NAFLD affects approximately a quarter of adults in developed countries.
The research, conducted by Dr Kushala Abeysekera and researchers from the University of Bristol, looked at data collected from 4,021 participants of the Children of the 90s study also known as Avon Longitudinal Study of Parents and Children (ALSPAC). Based in Bristol, participants from the health study -- who had previously been assessed for NAFLD as teenagers using ultrasound -- were invited for assessment using transient elastography with FibroScan as part of the Focus @24 clinic.
Researchers first looked at those participants who did not report harmful alcohol consumption and found that one in five had non-alcoholic fatty liver disease. On widening the data to include all participants, they again found that over 20 per cent displayed evidence of fatty liver and one in 40 had already developed fibrosis, with those participants who had both fatty liver and harmful alcohol use at greatest risk of liver scarring. As a comparison, at 17 years of age, 2.5 per cent of participants had moderate to severe levels of fatty liver, whilst at the age of 24 this number had increased to 13 per cent.
Dr Abeysekera, Honorary Lecturer in the Bristol Medical School: Population Health Sciences, explained: "Children of the 90s data has highlighted the potential importance of liver health amongst young adults. This age group remains a blind spot for clinicians, as they are typically considered a "healthy" age group that are rarely studied. If the obesity epidemic and culture of alcohol abuse aren't tackled nationally, we may see increasing numbers of patients presenting with end-stage liver disease, and at earlier ages.
"It is important to note that whilst we identified that 20 per cent of the cohort had fatty liver -- only a small percentage of the individuals will go on to develop cirrhosis (irreversible liver scarring), and the vast majority of participants should be fine if they manage their diet and exercise appropriately."
The next steps will be to take a closer look at how environmental and genetic factors may lead to individuals developing non-alcoholic fatty liver disease earlier in life.
https://www.sciencedaily.com/releases/2020/01/200115191527.htm