Background Recently factors in the relationship between gut microbiota, obesity, diabetes and the metabolic syndrome have been suggested in the development and progression of nonalcoholic steatohepatitis (NASH). In this sense, this work aims to evaluate the effects of probiotic supplementation on intestinal microbiota modulation, degree of hepatic steatosis and fibrosis, inflammation, gut permeability, and body composition. Methods This double-blind, randomized clinical trial will include adult outpatients with a diagnosis of NASH confirmed by biopsy with or without transient elastography. All patients will undergo a complete anamnesis to investigate their alcohol consumption, previous history, medications, nutritional assessment (dietary intake and body composition), sarcopenia, physical activity level and physical and functional capacity, cardiovascular risk, biochemical parameters for assessment of inflammatory status, lipid profile, hepatic function, gut permeability, and assessment of microbiota. These procedures will be performed at baseline and repeated after 24 weeks (at the end of the study). Through the process of randomization, patients will be allocated to receive treatment A or treatment B. Both patients and researchers involved will be blinded (double-blind study). The intervention consists of treatment with a probiotic mix (Lactobacillus acidophillus + Bifidobacterium lactis + Lactobacillus rhamnosus + Lactobacillus paracasei, 1 x 109 CFU for each) and the placebo which is identical in all its characteristics and packaging. Patients will be instructed to consume two sachets/day during 24 weeks and to report any symptoms or side effects related to the use of the sachets. Adherence control will be carried out through the patient’s notes on a form provided, and also by checking the number of sachets used. Discussion The final results of study will be analyzed and disseminated in 2020. Trial registration ClinicalTrials.gov, ID: NCT03467282. Registered on 15 March 2018.

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Objectives Evaluate the effect of probiotic supplementation on liver function markers, and clinical parameters, in nonalcoholic steatohepatitis (NASH) patients. Methods This double-blind, randomized clinical trial included adult outpatients with biopsy-proven NASH. The intervention: 24 weeks of supplementation with probiotic mix (Lactobacillus acidophillus + Bifidobacterium lactis + Lactobacillus rhamnosus + Lactobacillus paracasei, 1 × 109 CFU for each) or placebo, twice a day. At baseline and 24-weeks after treatment, the following parameters were evaluated: demographic and clinical data, hepatic enzymes, laboratory assessment, serum concentration of toll-like receptor-4 (TLR-4), cytokeratin 18 (CK-18) biomarker and anthropometric data assessment. Results Forty-four patients completed the trial (51.4 ± 11.6 years, 59% women). At baseline, 87% had low hepatic fibrosis degree (26% F0; 61% F1 at biopsy), values of hepatic enzymes close to normal [AST 32 (24–46) U/L, ALT 42 (28–63) U/L, GGT 46 (28–84) U/L], increased waist circumference (104.7 ± 12 cm), body mass index (BMI) with obesity classification 30.97 (28.36–33.75) kg/m2 and 76% with Metabolic Syndrome (MetS). After 24 weeks, no differences were observed between the Probiotic and Placebo groups in the components of the MetS, waist circumference, BMI or liver enzymes (P > 0.05 for all). CK-18 was reduced in both groups after the intervention: in the probiotic group from 981.09 (738.34–1134.73) to 639.46 (509.50–817.23) mIU/ml (P ≤ < 0.01) and in the placebo group from 789.74 (540.80–985.65) to 605.45 (472.13–837.22) mIU/ml (P = 0.013), however with no significant difference between groups (P = 0.109). Likewise, TLR-4 was reduced in both groups after the intervention, also with no difference between groups (P = 0.885). Conclusions The intervention with probiotics for 24 weeks in patients with NASH with low degree of fibrosis demonstrated to be unable to promote significant changes in the reduction of liver injury and inflammation biomarkers, nutritional and clinical parameters. Funding Sources Research and Events Fund from the Hospital de Clínicas de Porto Alegre (FIPE), Coordination for the Improvement of Higher Education Personnel (CAPES/PROAP), National Council for Scientific and Technological Development – Brazil (CNPq).