Abnormal gut microbiota metabolism specific for liver cirrhosis

Abstract

The gut microbiota has been neglected in precision medicine for a long time and is considered as the virtual endocrine organ of the human body (Evans et al., 2013; Clarke et al., 2014). The intestinal microbiome is made up of a diverse group of microorganisms, including bacteria, archaea, and eukaryotes, living together intimately. There are 300 to 1,000 different species living in the colon, which contains a densely-populated microbial ecosystem (Knight and Girling, 2003; Sears, 2005). However, 99% of the bacteria come from about 30 or 40 species (Knight and Girling, 2003; Sears, 2005). The human gastrointestinal microbiome plays an essential role in protecting the intestine, promoting nutrient absorption, resisting infection, and promoting the development of the immune system (Clarke et al., 2014). Gut microbiota can metabolize some xenobiotics such as phytochemicals, food toxicants, and drugs. The intestine-brain axis is a biochemical signaling pathway that includes the gut microbiota, central nervous system, and the neuroendocrine and neuroimmune systems. The gut microbiota can be considered as a large endocrine organ with the potential to produce nearly 100 kinds of products, which are absorbed into the blood and act on the distal organ. In the human body, the relationship between various microorganisms is mutually restricted, and the growth and decline of any one kind of microorganism may cause human diseases. There is ample evidence that complex metabolism and biochemical activities of intestinal microbiota are complementary with human physiology (Hooper et al., 2002; Turnbaugh et al., 2009; Qin et al., 2010). The gut microbiota operates as a whole and has a close relationship with human health and diseases (Qin et al., 2010). The intestinal microbiota has wide participation in cometabolism with the body and has remarkable influence on the metabolic phenotype of the host (Qin et al., 2012; Wei et al., 2016b). The liver is an important metabolic organ in the human body and has multiple functions, such as detoxication, secretory protein synthesis, glycogen storage, and so on. The liver has an intimate relationship with the gut through the physiological structure of the gut-liver axis (Szabo, 2015). The pathological mark of liver cirrhosis is hepatic fibrosis and portal hypertension, resulting in gastrointestinal congestion, tissue edema, slow gastric peristalsis, and intestinal permeability increase. Meanwhile, impaired liver function leads to the weakened ability to scavenge metabolites and decreased defense ability in patients; the combined effect of multiple factors leads to intestinal microenvironment imbalance and dysfunction. Many studies have shown that the intestinal microbiota community associated with cirrhosis is disordered, with a marked loss of Bacteroides and significant increases in Veillonella, Enterobacteriaceae, and Streptococcus. In addition, a distinct enhancement was detected in gut microbiota genes involved in material transport and metabolism, whereas a significant loss of cell cycle-related genes was detected in cirrhosis patients (Chen et al., 2011; Wei et al., 2013; Qin et al., 2014). During disease development, the intestinal microbiota is constantly adjusting itself and regulating the body's metabolism. For a biological organism, most of the functional proteins are classified as carbohydrate metabolism and amino acid metabolism pathways, and changes in some low-abundance proteins (such as cell communication, cell motility) are usually not so significant and are not easily detected.