Hepatobiliary surgery and nutrition | 2021
Are probiotics effective in reversing non-alcoholic steatohepatitis?
Abstract
HepatoBiliary Surg Nutr 2021;10(3):407-409 | http://dx.doi.org/10.21037/hbsn-21-85 The gut microbiota (GM) is an integrated ecosystem of tens of trillions of microorganisms, as actinomyces, archaea, protozoa, and last but not least viruses, including one thousand different species of known bacteria with an overall count of more than three million genes, 150 times more than the human genome. GM presents immunemodulating, absorptive and metabolic functions (1). Antibiotics first and more recently probiotics—alive microorganisms beneficially affecting human health— represent the most significant agents capable of modulating GM composition (1). In current clinical practice, single and multi-strain preparations of probiotics, are used in gastrointestinal and non-gastrointestinal diseases with curative significant and promising results. In particular, the multistrain VSL#3 is often used for the treatment and maintenance period of ulcerative colitis (2). The gutl iver ax i s cons i s t s o f the interact ion between GM, liver metabolism, and immune system; disruptions of this axis have been proved to be among the pathophysiological mechanisms associated with the onset and development of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), until liver cirrhosis and cancer development (HCC) (3). Functional studies have shown how altered GM can dysregulate the opening of inter-enterocytes tight-junctions (TJ), responsible for the maintenance of the adequate gut permeability to antigens, toxic substances from intestinal lumen until bloodstream and liver are reached (3). Antibiotics and probiotics can regulate the gut-liver axis and have beneficial effects on NAFLD, NASH, liver cirrhosis, and HCC presentation and prevention (3). To date, there is only scarce evidence on the efficacy of certain probiotics on liver fat deposition, down-regulation of the inflammatory cascade, improvement of metabolic parameters in animal models (Table 1), and remission of symptoms in patients with ulcerative colitis (2). Several animal models have shown that VSL#3 protects against NASH both in chemically-induced (dextran sulfate sodium-treated ApoE−/− mice) and diet-related (high fat diet-fed young rats and genetic ob/ob mice) setups (4). Moreover, in a particular diet-related NASH model, namely methionine-choline-deficient (MCD) diet-induced, VSL#3 failed to prevent both liver steatosis and inflammation although improved hepatic fibrosis (5). This finding is of great interest if compared to the possible impact on humans’ health. In fact, the ketogenic high-fat diet is often used for brief periods to lose weight in particular categories as obese and bodybuilders and resulting in improved insulin sensitivity (1). In light of these proven effects of VSL#3, the study of Jena et al. is of particular importance for the investigation of the potential effects of this multistrain probiotic preparation on several pathways of NASH development and carcinogenesis. The study employed a specific human-like animal model, farnesoid X receptor (FXR) knockout (KO) mice, which presented elevated BAs and developed steatosis and NASH, progressing spontaneously to liver cancer (4). These findings are consistent with previous works showing that inhibition of intestinal FXR signaling reduces obesity, insulin resistance, and fatty liver disease by modulation Viewpoint