The concept of BT has been extended from the traditional active intestinal flora to the mesenteric lymph nodes and other organs or parts outside the intestinal cavity through the intestinal barrier to the translocation of bacterial release products (such as endotoxin and bacterial DNA) [1]. In this paper, the mechanisms of bacterial translocation, especially the changes of intestinal flora and mucosal barrier function, and the immune defense mechanism are summarized as follows.

First, the mechanism of bacterial translocation

1.Intestinal cavity bacterial factor: The number of bacteria in the upper digestive tract is scarce, however, from the ileum, the microbial density increases sharply, from 105 colony forming units (CFU)/ml in the jejunum to 108CFU/ml in the distal ileum and cecum, and finally to/in the colon. The most easily displaced bacteria are pathogens temporarily existing in cells, which can resist the killing effect of phagocytes to some extent. Gram-negative bacteria (especially Escherichia coli, Klebsiella, pneumococcus, and other enterobacteriaceae), enterococci and other streptococci are most likely to migrate to mesenteric lymph nodes. In particular, the Escherichia coli strain appears to be more easily displaced, which may be because it has strong intestinal mucosal adhesion ability [2]. It has also been reported that the incidence of gram-positive bacteria (streptococcus) overgrowth in small intestine is very high in patients with liver cirrhosis, which can be compared with Escherichia coli [3]. Anaerobic bacteria rarely migrate, on the contrary, gram-negative aerobic bacteria easily migrate, even through intact intestinal epithelial cells. Overgrowth of intestinal bacteria is the key factor in the pathogenesis of bacterial translocation in liver cirrhosis. Clinical and experimental studies support this view. Oral antibiotics can significantly reduce the incidence of spontaneous bacterial peritonitis and intestinal bacterial overgrowth in patients with liver cirrhosis, and reduce the incidence of bacterial translocation and bacterial peritonitis in rats with liver cirrhosis. It has been observed that the slow intestinal transport may lead to the overgrowth of intestinal bacteria in experimental models of liver cirrhosis patients and rats. Pardo et al. [4] used cisapride, a gastrointestinal motility drug, in the ascites model of liver cirrhosis in mice, and observed that mice reduced the overgrowth of intestinal bacteria by enhancing the intestinal transport capacity, thus reducing the translocation of intestinal bacteria. This method was used to treat patients with liver cirrhosis and had the same effect. In addition, propranolol, a β -adrenergic receptor blocker, can accelerate intestinal transport, reduce intestinal bacterial overgrowth and block bacterial translocation in animal research [5].

The reasons for the slow peristalsis of small intestine are unclear, but they can be attributed to the following mechanisms: stimulation of sympathetic nerve, increase of nitric oxide synthesis, structural damage of intestinal mucosal barrier and oxidative damage of intestine. In addition to liver cirrhosis, oxidative damage also impairs gastrointestinal peristalsis in several other experimental conditions; Antioxidant treatment of oxidative damage can eliminate this effect [6].

2. Damage of intestinal mucosal barrier: It can be observed that not all overgrown intestinal bacteria migrate to mesenteric lymph nodes in the rat model of liver cirrhosis, suggesting that the mechanism of bacterial translocation in liver cirrhosis may include other factors besides overgrowth of intestinal bacteria, such as changes in the structure or function of intestinal mucosal barrier; Because portal hypertension may cause blood flow stagnation, the permeability of intestinal bacteria to blood vessels or lymphatic vessels increases. In the pathological observation of intestinal mucosa in rat model of liver cirrhosis and patients with liver cirrhosis, congestion and edema of intestinal mucosa can be seen, and the cell spacing becomes wider [7]. Increased permeability of intestinal cavity can be observed in the rat model of liver cirrhosis with bacterial translocation [8]. On the other hand, in several experimental models including portal hypertension in liver cirrhosis, the oxidative damage of intestinal mucosa may be due to local tissue hypoxia caused by portal hypertension, which leads to the increase of intestinal mucosal barrier permeability and the smooth migration of bacteria. It has been proved that antioxidant treatment can prevent the damage of ileum and cecum mucosa and bacterial translocation in rats with ascites due to cirrhosis [9].

3. Changes of local immune defense system: The mechanism of bacterial translocation in liver cirrhosis also involves changes of immune system. The immune defense mechanism of liver cirrhosis has a wide range of changes, including decreased phagocytic activity of reticuloendothelial system, lack of opsonin activity in ascites, and abnormal quality of neutrophils.

Second, the consequences of bacterial translocation

BT occurs frequently in patients with liver cirrhosis, especially those with severe liver dysfunction. The occurrence of BT indicates that the normal balance between host and intestinal flora has been broken, which can lead to repeated inflammatory reactions and easy to be complicated with infection [10]. Bacterial translocation is a key step in the pathogenesis of digestive tract-derived bacterial infections, mainly spontaneous bacterial peritonitis in cirrhosis. However, several studies have evaluated that bacterial translocation not only causes spontaneous bacterial peritonitis, but also causes the activation of immune system and high dynamic state of liver cirrhosis.

1.Spontaneous bacterial peritonitis and renal dysfunction: The traditional pathogenesis of spontaneous bacterial peritonitis is that bacteria from intestinal cavity pass through the intestinal wall and reach mesenteric lymph nodes and other organs. If the body's local immune defense system can't produce sufficient response, spontaneous bacterial peritonitis will further develop and produce ascites. Bacteremia and spontaneous bacterial peritonitis are the main consequences of bacterial translocation in liver cirrhosis, and bacterial infection is a common and serious complication in liver cirrhosis. Although most episodes of spontaneous bacterial peritonitis have achieved satisfactory results after rapid diagnosis and treatment, most patients still have complications related to infection, such as hepatic encephalopathy, septic shock, renal failure, leading to hepatorenal syndrome and even death.

The development of renal failure in patients with liver cirrhosis is attributed to the excessive production of nitric oxide and inflammatory cytokines such as tumor necrosis factor (TNF) α in infection. In recent years, scholars have observed that the combination of antibiotics and anti-tumor necrosis factor preparations can reduce the mortality of cirrhotic rats complicated with bacterial peritonitis, compared with untreated rats or only treated with antibiotics [1 1].

2. Activation of immune system: Overgrowth and translocation of intestinal bacteria are common in patients with ascites due to liver cirrhosis, which may lead to activation of monocytes and lymphocytes, increase the level of inflammatory cytokines and enhance the synthesis of nitric oxide in patients with liver cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide-binding protein, forming a complex of lipopolysaccharide and lipopolysaccharide-binding protein, which is connected with CD 14 and transduces signals to nested receptors, thus activating inflammatory factors. Therefore, lipopolysaccharide-binding protein can predict bacterial infection in patients with cirrhosis and ascites. Liver cirrhosis patients with elevated serum lipopolysaccharide binding protein level are in obvious immune activation state, and oral norfloxacin can improve immunity, suggesting that pathogenic intestinal bacterial products can activate immune system in patients with liver cirrhosis without concurrent infection. The activation of macrophages by endotoxin in patients with liver cirrhosis is considered to be related to the increase of tumor necrosis factor in blood circulation [12]. Toll-like receptor 4 is a lipopolysaccharide receptor of Gram-negative bacilli, which can activate mononuclear macrophages to produce proinflammatory factors such as interleukin (IL)- 1S, recombinant nuclear factor α, IL-6 and IL-8 [13]. As mentioned in earlier comments, in the presence of bacteremia and after bacterial translocation, cytokine cascade activation occurs, including the activation of inflammatory cytokines such as TNFα and IL-6. In patients with cirrhosis without obvious bacterial infection, bacterial products such as endotoxin and bacterial DNA may also stimulate the immune system. In recent years, bacterial DNA[ 14] has been detected in aseptic ascites (negative culture and no neutrophils found) and serum of patients with liver cirrhosis, and most of the DNA fragments have been identified as derived from Escherichia coli by nucleotide sequence determination. This bacterium is also the most common cause of spontaneous bacterial peritonitis in patients with liver cirrhosis. Interestingly, the detection of bacterial DNA is consistent with the persistent existence of the same bacteria in different periods, and with the disappearance or reappearance of bacteria in continuous serum and ascites samples, suggesting that the migration of bacterial products from mesenteric lymph nodes to blood and other body fluids is a dynamic process. Bacterial DNA can activate the immune system. Compared with patients without bacterial DNA, monocytes and macrophages of patients with liver cirrhosis with bacterial DNA in blood and ascites produce more cytokines.

3. Hyperdynamic circulatory state in patients with liver cirrhosis: Patients with ascites due to liver cirrhosis are often complicated with hyperdynamic circulatory state, which is characterized by decreased vascular resistance and average arterial blood pressure, and increased heart rate, cardiac output and local blood flow. Studies have shown that the excessive production of several vasodilators, such as prostaglandin, adrenal regulatory protein, glucagon, substance P and other substances, seems to be the initial step, and the increase of nitric oxide synthesis is the main reason for the hemodynamic changes of liver cirrhosis. Secondly, endotoxemia is also very important in the development of hyperdynamic circulation in liver cirrhosis. In addition, endotoxin can promote the synthesis of inflammatory cytokines such as TNFα, among which TNFα is related to the high dynamic state of cirrhotic rats and portal hypertension of non-cirrhotic rats.

In addition, bacterial translocation is accompanied by the appearance of endotoxin in mesenteric lymph nodes and blood. These studies suggest that intestinal translocation of bacteria or their products, such as endotoxin, can worsen the changed circulatory state. The evidence supporting this hypothesis shows that the existence of bacterial DNA induces the further activation of ascites leukocytes in patients with severe cirrhosis. This leads to excessive production of nitric oxide in culture, and there is a significant correlation between nitric oxide level and inducible form of nitric oxide synthase [15].

Reducing bacterial translocation is helpful to improve hemodynamic disorder in patients with liver cirrhosis. Bacterial DNA or LBP in serum can develop into an effective marker of bacterial translocation, which can help us evaluate whether the treatment measures for patients with liver cirrhosis are feasible and beneficial. BT plays an important role in liver cirrhosis complicated with infection and hyperdynamic circulatory state, and the latter is a key factor in the formation of portal hypertension, ascites and hepatorenal syndrome [8]. Bacterial translocation has been concerned in many fields. In short, it is of great significance to prevent the occurrence of liver cirrhosis complicated with infection and other complications by studying BT, but it is greatly limited in clinic because of the lack of non-invasive and sensitive research methods.