Abstract

Treatment for non-alcoholic fatty liver disease (NAFLD) currently consists of lifestyle modifications such as a low-fat diet, weight loss, and exercise. The gut microbiota forms part of the gut–liver axis and serves as a potential target for NAFLD treatment. We investigated the effect of probiotics on hepatic steatosis, fibrosis, and biochemical blood tests in patients with NAFLD. At the small intestinal mucosal level, we examined the effect of probiotics on the expression of CD4+ and CD8+ T lymphocytes, as well as the tight junction protein zona occluden-1 (ZO-1). This was a randomized, double-blind, placebo-controlled trial involving ultrasound-diagnosed NAFLD patients (n = 39) who were supplemented with either a probiotics sachet (MCP® BCMC® strains) or a placebo for a total of 6 months. Multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species at a concentration of 30 billion CFU were used. There were no significant changes at the end of the study in terms of hepatic steatosis (probiotics: −21.70 ± 42.6 dB/m, p = 0.052 vs. placebo: −10.72 ± 46.6 dB/m, p = 0.29) and fibrosis levels (probiotics: −0.25 ± 1.77 kPa, p = 0.55 vs. placebo: −0.62 ± 2.37 kPa, p = 0.23) as measured by transient elastography. Likewise, no significant changes were found for both groups for the following parameters: LiverFAST analysis (steatosis, fibrosis and inflammation scores), alanine aminotransferase, total cholesterol, triglycerides, and fasting glucose. In the immunohistochemistry (IHC) analysis, no significant expression changes were seen for CD4+ T lymphocytes in either group (probiotics: −0.33 ± 1.67, p = 0.35 vs. placebo: 0.35 ± 3.25, p = 0.63). However, significant reductions in the expression of CD8+ T lymphocytes (−7.0 ± 13.73, p = 0.04) and ZO-1 (Z-score = −2.86, p = 0.04) were found in the placebo group, but no significant changes in the probiotics group. In this pilot study, the use of probiotics did not result in any significant clinical improvement in NAFLD patients. However, at the microenvironment level (i.e., the small intestinal mucosa), probiotics seemed to be able to stabilize the mucosal immune function and to protect NAFLD patients against increased intestinal permeability. Therefore, probiotics might have a complementary role in treating NAFLD. Further studies with larger sample sizes, a longer duration, and different probiotic strains are needed to evaluate the real benefit of probiotics in NAFLD.

Highlights

  • Non-alcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis in the absence of other causes of heavy hepatic fat accumulation, such as heavy alcohol intake

  • As our understanding of the pathogenesis of NAFLD has evolved, it has been suggested that disturbances in the gut microbiota composition, leading to gut dysbiosis that can lead to gut–liver axis derangement, is one of the possible factors that triggers local inflammatory cascades [4,5]

  • We failed to demonstrate a significant improvement in the expression of CD8+ T lymphocytes and zona occludens-1 (ZO-1) for the probiotics group, we revealed no significant reduction in their expression, unlike in the placebo group

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Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis in the absence of other causes of heavy hepatic fat accumulation, such as heavy alcohol intake It is one of the most common causes of chronic liver disease nowadays. A recent meta-analysis on the prevalence of NAFLD in Asian countries (n = 237 studies with 13,044,518 individuals as pooled participants), revealed an overall NALFD prevalence of 29.6%, with an increasing prevalence trend over time (1999–2005: 25.3%; 2006–2011: 28.5%; 2012–2017: 33.9%) [2] This has given rise to a new epidemic in chronic liver disease and increased disease burden. Treatment options for the NAFLD are limited and mainly revolve around lifestyle interventions such as weight loss via dietary therapy and exercise [3] It has to be treated early owing to its tendency to progress to end-stage liver cirrhosis and the possible subsequent complication of hepatocellular carcinoma. Probiotics present a possible target of treatment by manipulating the gut microbiota and modulating intestinal permeability and local mucosal inflammation

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