Graz, Austria – A groundbreaking study from the Medical University of Graz has shed light on a crucial connection between liver cirrhosis and muscle wasting, known as sarcopenia. Affecting nearly half of all cirrhosis patients, this condition can become so severe that it hinders life-saving surgeries. Researchers have identified the intestinal microbiome as a pivotal factor in this process, suggesting new therapeutic avenues that could significantly impact patient care.
The body's ecosystem: the role of gut bacteria
The human body, much like an ecosystem, is home to trillions of microorganisms that aid in digestion, immune defence, and more. However, an imbalanced gut microbiome has now been linked to sarcopenia in patients with chronic liver disease. Austria, with over 1,100 cases per 100,000 people, ranks second in Europe for chronic liver disease prevalence, trailing only Romania.
Unveiling the liver-muscle connection
The research project, funded by the Austrian Science Fund (FWF) and titled 'The gut-liver-muscle axis in liver cirrhosis', pinpointed specific bacterial strains that proliferate when liver cirrhosis coincides with muscle wasting. Gut bacteria convert primary bile acids into secondary bile acids, and the study revealed that an altered microbiome led to an excess of these secondary bile acids in participants.
'The results suggest that these bile acid products enter the muscle via the bloodstream, causing damage,' explained Vanessa Stadlbauer-Köllner, the principal investigator and Professor of Translational Microbiome Research and Hepatology. Her goal is to develop new therapies that specifically target the intestinal microbiome.
New insights into bile acids
The study involved 217 participants with and without liver cirrhosis, categorised by the presence or absence of sarcopenia. Researchers discovered that bacterial strains like Bacteroides fragilis, Blautia marseille, Sutterella spp., and Veillonella parvula were more common in those with muscle wasting. Conversely, Bacteroides ovatus appeared beneficial, being present in those without sarcopenia despite having cirrhosis. The detrimental strains produced higher levels of secondary bile acids.
Initially, bile acids were thought to merely aid fat digestion. 'Now we understand that these substances can act as hormones affecting other cells,' Stadlbauer-Köllner noted. Laboratory tests indicated that secondary bile acids damage muscle cells. Stadlbauer-Köllner plans to explore if this damage occurs in humans, hypothesising that these substances enter the bloodstream through a compromised intestinal barrier in chronically ill individuals.
The serious issue of muscle wasting
Sarcopenia poses significant challenges, particularly in chronic diseases and ageing. Stadlbauer-Köllner, who leads the internal medicine liver transplant outpatient clinic in Graz, emphasised, 'Muscle atrophy can be so severe that patients are too weak for liver transplants.' Most individuals are unaware of their condition until severe complications necessitate hospitalisation. Liver cirrhosis, often the culmination of hepatitis infections, alcohol use, autoimmune diseases, or metabolic disorders like obesity and diabetes, typically develops over extended periods.
Towards targeted therapies
The identification of harmful bacterial strains is a crucial step toward developing targeted therapies to promote beneficial gut bacteria. Stadlbauer-Köllner is also investigating a drug containing special amino acids that may positively affect the microbiome and muscle health. The FWF-funded project lays the groundwork for these innovative treatments. 'This funding programme is invaluable for medical research,' Stadlbauer-Köllner remarked, highlighting its role in advancing independent therapeutic research.
Public interest in the gut microbiome has surged, partly due to the approval of the first microbiome-targeting drug in the USA last year. However, Stadlbauer-Köllner cautions, 'While there is immense potential in microbiome research, much foundational work remains to be done.'
This pioneering research underscores the vital interplay between the gut microbiome, liver health, and muscle integrity, offering hope for improved treatments and patient outcomes.
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