Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. In an aggressive type, non-alcoholic steatohepatitis (NASH) might lead to cirrhosis and hepatocellular carcinoma progression. Currently, there is no certified drug applied to treat NASH (1).
The pathogenesis path of NASH is yet remained to be known. However, the underlying factors mentioned below could be taken into account: obesity, high-calorie/high-fat diet, diabetes, hypercholesterolemia, and certain drugs either(2). Over this issue, efforts done to alter people’s lifestyles have been suggested. Still, they were hardly sustainable, so it necessitates to conduct investigations through some new therapeutic strategies, including weight reduction and diet changes, which are recommended as the first step involved in patients' treatment procedure under such conditions (3).
Once weight loss is obtained and appropriately sustained, it may gradually improve NAFLD(1). Although there is no recognized medication or surgical method approved for the treatment of NAFLD, countless numbers of clinical trials have demonstrated several pharmacological treatments suitable to cure NAFLD/NASH, such as diabetes medications, lipid-lowering drugs, antioxidants, and anti-tumor necrosis factor (TNF)-α agents(4).
The mechanisms related to the development and progression of NAFLD are yet to be fully understood. This process is assumed to be the substantial consequence of the interactions amongst progressive environment-driven epigenetic code changes, genetic background, and molecular alterations. Environmental factors such as unhealthy diet and the appearance of a stagnant sedentary routine, which drive epigenomic reprogramming of the host genome via post-translational modifications of gene expression, could ultimately evolve phenotypic changes in the organism(5). Seamlessly, obesity is thought to be the most vital risk factor affiliated with various NAFLD series in which abdominal fat is correlated with a volume of steatosis observed on liver biopsy(1) with a striking increased risk of insulin resistance and emerging multiple diseases in children as in adults(6).
NAFLD often gives rise to dyslipidemia in which increased serum TG and LDL-C levels and decreased HDL-C levels could be demonstrated (7). Additionally, recent evidence suggested an interaction between the liver and gut called the ‘gut-liver axis’ might participate in the evolution of phenotypic replacement from NAFL to a much more severe state like NASH NASH-related fibrosis. Indeed, NAFLD is associated with escalating intestinal permeability (IP) and small intestinal bacterial overgrowth (SIBO) in humans, all connected to the severity of hepatic steatosis. Hence, several studies have introduced gut microbiota modulation via probiotics, prebiotics, and synbiotic as an efficacious solution to improve the obesity state and subsequent NAFLD(5).
The World Health Organization considers probiotics as live microorganisms that positively impact the intended host as long as administered in sufficient volumes. The prophylactic and therapeutic impacts of these microorganisms, including the equilibration of intestinal microbiota, diminution in cholesterol levels, hypertension enhancement, diabetes, lactose intolerance, gastrointestinal diseases, immune system improvement, and also plummeting the risk of various cancers, have been reported in different trials(7). Administration of Lactobacillus and Bifidobacterium probiotic strains, prebiotics, synbiotics (blend of probiotics and prebiotics), and their fusion with nutraceuticals have been represented to be advantageous by dwindling the hepatic triglyceride content, the hepatic tissue inflammation, total body and visceral adipose tissue weight, and also by improving the insulin sensitivity in various animal models suffering NAFLD and have a deeply profound effect on NASH either(4). In addition to this, probiotics can make a decline in the activity of Jun N-terminal kinase and nuclear factor κb and also make an increase in the number of natural killer T cells located in the liver. However, other conducted animal studies could not demonstrate an impact on hepatic steatosis and necroinflammation improvement. Probiotics prevented liver fibrosis through the exertion of several alterations over the expression of TGFꞵ. It remains unclear whether probiotics are beneficial in human patients suffering NASH(3).
Due to the lack of appropriate studies and the emerging requirements for further illustration over the effects of probiotics on the treatment of NAFLD and NASH-related disorders in humans, in this study, we seek to evaluate and provide evidence related to the effects of probiotics on the treatment of NAFLD.