Nonalcoholic fatty liver disease is the leading cause of liver disease worldwide and can progress to nonalcoholic steatohepatitis (NASH) through physical inactivity and gut dysbiosis. Exercise training reverses gut dysbiosis in non-NASH persons with obesity and in NASH animal models.

In collaboration with researchers at the University of California San Diego and Juniata College, Dr. Jonathan Stine and his research team conducted the first study to investigate the effects of exercise training on gut microbiome in patients with NASH. The study analyzed stool samples from six subjects who were participating in the NASH Fitness Intervention in Thrombosis (NASHFit) Trial before and after 20-weeks of exercise training.

Using 16S ribosomal RNA and metatranscriptomics analysis, the study demonstrated that exercise training reverses gut dysbiosis in patients with NASH as greater microbial and functional diversity were observed after exercise training. Researchers also found that exercise training enriched certain bacteria, including Parabacteroides distasonis, low levels of which lead to the development of NASH and increase cardiovascular risk. Enrichment of Parabacteroides distasonis enrichment created multiple positive co-occurring relationships with commensal gut organisms, including Lachnospiraceae and Ruminococcaceae, each of which may lessen "leaky gut," promote gastrointestinal health and interrupt disease progression in NASH. Metatranscriptomics also demonstrated 31 genes were enriched after exercise training, including several genes involved in NASH pathogenesis, offering additional novel explanations for how exercise training can improve this common condition.

These findings require validation in a randomized controlled trial. If validated, new treatments beyond exercise that target microbiome manipulation may be discovered for NASH patients.