The Human Gut Microbiome in Liver Diseases

Abstract

Recent advances in culture-independent laboratory techniques and bioinformatics have contributed to enriched characterizations of the gut microbiota and microbiome in chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, primary biliary cholangitis, and cirrhosis. In this review, the authors focus on studies characterizing and modulating the gut microbiota and microbiome in humans. The majority of studies that characterized microbiota involved a small number of patients using 16S ribosomal RNA genetic sequencing. Few studies applied whole-genome shotgun sequencing and metagenomics analyses. The majority of clinical trials on modulating the microbiome have focused on probiotics or antibiotics in small groups of patients with cirrhosis versus healthy controls. Several trials are underway using fecal microbial transplantation in alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, and cirrhosis. Future research is needed on understanding the viral and fungal microbiome and developing user-friendly microbiome tools.

Modulation of bile acid profile by gut microbiota in chronic hepatitis B

“…Bile acids, synthesized in the liver, are metabolized by gut bacteria in intestine and are critical for maintaining the host metabolism . The changes of bile acid profiles in different liver conditions are inconsistent .…”

“…Bile acids, synthesized in the liver, are metabolized by gut bacteria in intestine and are critical for maintaining the host metabolism. 24,28 The changes of bile acid profiles in different liver conditions are inconsistent. [4][5][6][7] Growing evidences suggested that cirrhosis is closely related with bile acid metabolism.…”

Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

“…BT promotes the immune system exacerbation (20) and further increases the risk of progression to acute levels in chronic liver failure (21,22). There is evidence on both quantitative and qualitative changes in gut microbiota composition during development of liver damage (23) and how dysbiosis impacts disease progression (24,25). As a result, the host-microbiome interaction is also unstable, and the gut epithelial barrier is affected beyond disease-derived inflammation (26).…”

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

“…Every human being harbors at least 4 × 10 13 colonizing microbial cells [31] and more than 10 million non-redundant microbial genes in their gut [32,33]. There is sufficient evidence that changes in microbiota impact on the progression of liver disease (elegantly summarized in recent reviews [33][34][35]) and that profound changes in the microbiota occur with the development of liver cirrhosis [36], while underlying mechanisms remain not yet fully explored. There are key players in this interaction, such as an impaired epithelial barrier, in cirrhosis known as 'leaky gut' [33][34][35], with bacteria or metabolites entering into the portal blood circulation, interacting with immune cells and reaching the hepatic microcirculation, where they interact with nonparenchymal and parenchymal liver cells.…”

“…There is sufficient evidence that changes in microbiota impact on the progression of liver disease (elegantly summarized in recent reviews [33][34][35]) and that profound changes in the microbiota occur with the development of liver cirrhosis [36], while underlying mechanisms remain not yet fully explored. There are key players in this interaction, such as an impaired epithelial barrier, in cirrhosis known as 'leaky gut' [33][34][35], with bacteria or metabolites entering into the portal blood circulation, interacting with immune cells and reaching the hepatic microcirculation, where they interact with nonparenchymal and parenchymal liver cells. The liver also secretes bile acids, which in turn modify the intestinal microbiome and, also, act as signaling molecules between the cirrhotic liver, the gut microbiota, and the intestine [37].…”