RE and Probiotics in MAFLD/NAFLD

This project aims to evaluate the roles of the autonomic nervous system (ANS) and gut microbiota as correlates of clinical improvement in metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD) in response to a therapeutic regimen comprising resistance exercise and probiotic supplementation. The primary objective is to investigate the effects of these non-pharmacological interventions on MAFLD/NAFLD and to identify patient phenotypes based on baseline ANS profiles and gut microbiota composition that predict clinical responses.

Study population: Patients diagnosed with non-alcoholic or metabolically mediated fatty liver disease (NAFLD/MAFLD), including the inflammatory form (NASH), confirmed by imaging (ultrasound, MRI-PDFF) or histopathological (liver biopsy) methods. Inclusion criteria: * Diagnosis of NAFLD/MAFLD or NASH (imaging or histological confirmation of fatty liver disease, e.g., ultrasound, MRI-PDFF, biopsy) * Age 18-60 years * Ability to understand the study procedures and provide informed consent. * Stable clinical condition for at least 3 months prior to study initiation. Exclusion criteria: * Lack of fluency in English or Polish * Significant (structural) limitation of upper and/or lower limb mobility * Pregnancy or breastfeeding * Inability to understand instructions * Shift work * Participation in any study or research project within the last 3 months * Participation in an interventional drug study within the last 3 months * Participants with hepatic steatosis and regular alcohol consumption \> 30 g/day * Individuals with any concomitant liver disease (viral hepatitis, drug-induced liver injury, metabolic/genetic diseases (e.g., Wilson's disease)) * Anticoagulant/antiplatelet therapy, antithrombotic therapy, immunosuppressive medications, prolonged immunosuppression (e.g., recent cytotoxic chemotherapy, HIV infection with CD4 count \< 240), antibiotics, corticosteroids, valproic acid, amiodarone, tamoxifen within 3 months prior to study enrollment * Use of medications such as steroids, methotrexate, metformin * Use of agents such as vitamin E, omega-3 fatty acids, or medications with evidence of an effect on NAFLD (pioglitazone, GLP-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid) * Active or previous history of invasive cancer (excluding curatively treated carcinoma in situ \[e.g., cervical\] or benign skin cancer), unless complete remission has been achieved * Regular use of probiotic or prebiotic supplements within 3 months prior to study enrollment * Known allergy to probiotics * History of using an alternative diet within 3 months prior to study enrollment or changing diet during study entry * Previous surgery (bariatric surgery, gastric or intestinal resection) * Parenteral nutrition (TPN) within the last 6 months * Insulin therapy * Uncontrolled diabetes * Cardiovascular disease (e.g., uncontrolled blood pressure, coronary artery disease, NYHA class III-IV heart failure, severe arrhythmias, orthostatic intolerance) * Nervous system disorders * Cognitive impairment and dementia * Osteoporosis/osteopenia * Active thyroid disease * Cushing's syndrome * Any implanted battery-powered device (e.g., AICD, pacemaker, cardiac rhythm recorder, cochlear implant)