**1. Introduction**

Nonalcoholic fatty liver disease (NAFLD) represents the accumulation of fat of more than 5% of liver cells, not related to alcohol abuse. It can manifest as simple steatosis, inflammation with hepatocytes necrosis, known as nonalcoholic steatohepatitis (NASH), or in serious situations as end-stage chronic liver disease (NASHrelated cirrhosis) with severe fibrosis and architectural damages [1, 2]. Over the past few decades, given the increased incidence of metabolic syndrome, NAFLD

became a leading actor in liver diseases, with an exponentially upward trend, especially in developed countries [3]. As result, NAFLD features as a problem of public health due to its evolutionary potential with propensity of development fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality, not to mention the increase risk for cardiovascular diseases in conjunction to associated metabolic issues [4, 5].

The development of NAFLD/NASH could be triggered by multiple conditions such as genetic disorders, particularities of life style and diet with high intake of carbohydrates and fats, hormones imbalance and insulin resistance, host-derived features like age, ethnicity, gender, antibiotic use, and inflammatory state, as well as imbalance of gut microbiota [6].

Procalcitonin (PCT), a peptide 13-kD glycoprotein, which is a precursor of calcitonin, without hormonal activity, rises in serum as a response to proinflammatory conditions, especially related to those of bacterial origin. In this context, PCT along with C-reactive protein (CRP), interleukins (ILs), and various cytokines could be considered as an acute phase reactant [7, 8].

Interestingly, while PCT levels should decline in patients with liver diseases and hepatocytes insufficiency, however, it was observed an increase of those levels, even without a bacterial infection. Those observations shed a new light upon the relation PCT and liver conditions. In patients with acute liver failure, it seems that procalcitonin elevation is not related to bacterial infection but more to cellular injury [9, 10].

The relation between NAFLD and gut microbiota dysbiosis was observed three decades ago in rats with blind intestinal loop and small intestinal bacterial overgrowth [11]. Gut microbiota dysbiosis could intervene in NAFLD pathogenesis by modulating the energy metabolism and insulin resistance, increasing free fatty acids (FFA), decreasing choline production, increasing gut permeability, upregulating hepatic de novo lipogenesis and triglyceride synthesis, releasing hepatotoxic compounds, eliciting endogenous alcohol production, and eventually producing hepatocyte's fat accumulation as droplets of triglycerides [12].

Some studies have demonstrated that gut microbiota dysbiosis may be involved in the perturbation of the hepatic metabolism of carbohydrates and lipids that consecutively could disturb the balance between pro- and anti-inflammatory local liver cytokines, giving the possibility of development NAFLD or NASH [13].

The so-called gut-liver axis represents not only a proximity anatomical relationship but also a perfect functional link between liver and the gastrointestinal tract. Through this axis, a direct connection is made, so that many metabolites related to the gut microbiota could rapidly reach receptors located at the liver surface and consecutively trigger the activation of numerous pathogenic pathways, resulting in serious events such as insulin resistance, liver inflammation, hepatocyte destruction, and fibrosis [14, 15].

The increase of gut permeability seems to play an important role in NAFLD by releasing into the portal vein stream of several substances resulted from bacterial metabolism, such as lipopolysaccharides (LPS), bacterial components, short-chain fatty acids (SCFAs), bile acids (BAs), choline metabolites, and endogenous ethanol that reach the liver and seem to contribute to the pathogenesis of NAFLD [16].

A human study based on histology-proven fatty liver (FL) disease has demonstrated that the severity of NAFLD is related not only to gut microbiota dysbiosis per se but also to important metabolic functional modifications of the gut microbiome. It was observed that *Bacteroides* sp. were significantly increased in patients with NASH and *Ruminococcus* sp. were associated to higher stages of fibrosis: F ≥ 2. The authors

attempted to make a stratification of NAFLD related to enterotypes of gut microbiota and hypothesized that the imbalance of microbiota could be used as a possible predictor of NAFLD [17].
