Probiotic Lysate (Postbiotic and Metabiotic) Supplementation for Adults NAFLD Patients (DELI_NAFLD Study)

The current study aim was to conduct placebo-controlled randomize clinical trial to assess the short-term efficacy and safety of postbiotics on hepatic fat content as measured by MRI-PDFF and ultrasonography, liver stiffness (LS) measured by Shear Wave Elastography (SWE) and anthropomorphic variables in NAFLD patients. The study will include 3 periods. Screening period of up to 1 weeks to assess the eligibility to inclusion/exclusion criteria. Treatment period for 3 month where the participants will receive a twice daily oral dose of postbiotics (cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023) at the assigned dose of 100mg or placebo in capsules. During this period monthly phone contacts will be done for assessment of compliance and safety concerns. Follow-up period of up to 3 month.

Inclusion Criteria: * adult participants (ages 18-70) * presence of NAFLD diagnosed according to the recommendations of the American Gastroenterology Association (AGA) and American Association for the Study of Liver Disease (AASLD); * the diagnosis of fatty liver was based on the results of abdominal ultrasonography. Of 4 known criteria (hepato-renal echo contrast, liver brightness, deep attenuation, and vascular blurring), the participants were required to have hepato-renal contrast and liver brightness to be given a diagnosis of NAFLD * MRI-PDFF of at least 6.4%; * BMI 25-39.9 kg/m2; * aspartate transaminase (AST) and alanine transaminase (ALT) ≤3x upper limit of normal; * written informed consent. Exclusion Criteria: * recent hepatitis, or positive screening test for hepatitis B (hepatitis B virus surface antigen) or hepatitis C (hepatitis C antibody); * alcohol abuse (\>20 g/day (2 standard drinks) in women or \> 30 g/d (3 drinks) in men over a two-year period); * drug-induced liver disease, Wilson's disease, hereditary deficiency of antitrypsin-1 and idiopathic hemochromatosis; * history of decompensated liver disease including ascites, encephalopathy or variceal bleeding; * regular use of an agents with gut microbiota modulation activity (antibiotic, pro-, pre-, post or synbiotics supplement etc.) within 3 months prior to enrollment; * allergy on probiotics or their components; * use of agents such as vitamin E, omega-3 fatty acids or medications with evidence for effects on NAFLD (pioglitazone, GLP-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid); * subjects with a history of bariatric surgery or significant weight loss (\> 5% body weight) or rapid weight loss (\> 1.6kg/week), within 6 months prior to enrollment; * uncontrolled cardiovascular or respiratory disease, decompensated liver disease including ascites, encephalopathy or variceal bleeding, active malignancy, or chronic infections; * participant who had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks prior to enrollment; * participation in other clinical trials; * presence of pregnancy or lactation.