Effect of probiotic supplementation in nonalcoholic steatohepatitis patients: PROBILIVER TRIAL protocol

Abstract

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.

Evaluation of the role of kefir in management of non-alcoholic steatohepatitis rat model via modulation of NASH linked mRNA-miRNA panel

“…Currently, several NAFLD therapies are being targeted to improve insulin resistance (IR), but there is no effective treatment 33 . Probiotic treatment was shown to improve NASH through modulating insulin resistance, the key factor which plays a major role in the development of a serious liver condition 34 . Due to correlation between small intestinal bacterial overgrowth (SIBO) and NAFLD observed in experimental and clinical studies 35,36 , probiotics could also delay disease progression and prevent complications by modulating intestinal flora, intestinal permeability, and inflammatory response 37 .…”

Modulation of hepatic mRNA-miRNA panel linked to NAFLD/NASH Hippo signaling and gut microbiota after administration of kefir in Non-Alcoholic Steatohepatitis Rat Model

“…Currently, several NAFLD therapies are being targeted to improve insulin resistance (IR), but there is no effective treatment [24]. Probiotic treatment was shown to improve NASH through modulating insulin resistance, the key factor which plays a major role in the development of a serious liver condition [25]. Due to correlation between small intestinal bacterial overgrowth (SIBO) and NAFLD observed in experimental and clinical studies [26], [27], probiotics could also delay disease progression and prevent complications by modulating intestinal ora, intestinal permeability, and in ammatory response [28] .…”

“…At the end of the study, rats were fasted for 12 hrs and anesthetized with one dose of urethane (1.2 g/kg, IP) [25] for sacri cing. Blood samples were collected from retro-orbital vein, centrifuged at 3000 rpm for 10 min for serum separation, then aliquoted and stored at −20°C for subsequent biochemical analysis.…”

Nonalcoholic Fatty Liver Disease: Modulating Gut Microbiota to Improve Severity?

“…Interestingly, an on-going RCT will evaluate whether 24-weeks of a probiotic mix efficiently reduces liver fibrosis by transient elastography in NAFLD patients. 100 .…”