Abstract
Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels. Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone. Before and after the intervention we assessed steatosis by magnetic resonance imaging, intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing. NASH patients presented high gut permeability, but low prevalence of SIBO. After the intervention, only the synbiotic group presented a reduction in steatosis, lost weight, diminished BMI and waist circumference measurement. Synbiotic did not improve intestinal permeability or LPS levels. We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in Western countries, and it is predicted that by 2030 this disorder will be the most common indication for liver transplantation worldwide [1]
In order to confirm the diagnosis of nonalcoholic steatohepatitis (NASH), an experienced pathologist who was blinded to the clinical data reviewed all but one slide and scored steatosis, lobular inflammation, ballooning injury and fibrosis according to the NASH Clinical Research Network (CRN) system: steatosis affecting
The grades of steatosis, lobular inflammation, ballooning and fibrosis identified in the liver biopsies performed before inclusion in the study were similar between the groups
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in Western countries, and it is predicted that by 2030 this disorder will be the most common indication for liver transplantation worldwide [1]. NAFLD encompasses a spectrum of liver disorders characterized by hepatic steatosis that cannot be assigned to alcohol consumption. Recent evidence suggests that NAFLD is a multisystem disease that is not confined to liver-related morbidity and mortality, and affects regulatory pathways and extra-hepatic organs increasing the risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases [3]. Several clinical trials have been performed to identify a pharmacologic agent to treat NAFLD/NASH [4,5,6,7,8,9], but currently there is no approved specific drug for the treatment of this condition [10].
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