The gut-brain axis is a bidirectional messenger system between the central nervous system (CNS) and the gastrointestinal tract, in which major role is played by gut microbiota. The gut microbiota creates a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, also known as microbiota-gut-brain axis. The microbiota-gut-liver-brain axis facilitates the occurrence and development of many diseases, and provides a direction for the research of disease treatment. 

The study reviewed the role of the gut microbiota in the irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), functional dyspepsia (FD), non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), cirrhosis and hepatic encephalopathy (HE) via the gut-liver-brain axis, and their potential mechanisms based on the understanding of the microbiota-gut- liver-brain axis are highlighted.IBS is a common functional disease that presents as abdominal pain or discomfort accompanied by changes in bowel habits without organic lesions. It is considered as most common chronic visceral pain syndrome. Internal and external regulatory factors related to the development of the disease include heredity, dietary intake, gastrointestinal infections, increased intestinal permeability, low inflammation, bile salt metabolism disorders, abnormal serotonin metabolism, CNS dysfunction, visceral allergies, gut microbiota imbalance. Plethora of evidence suggests that alterations in the gut-brain axis contributes in the pathophysiology of IBS. The interaction of brain, gut and gut microbial metabolites is key pathophysiological foundations of IBS. These metabolites are mainly implicated in the subcortex along with cerebral cortex, that have the potential to change the perception of pain in patients with IBS and may be mediated by microbial regulation of the intestinal serotoninergic system.IBD is a chronic immune-mediated inflammatory disease of the intestinal mucosal tissues that presents itself in two forms; Crohns disease (CD) and ulcerative colitis (UC). CD is typified by transmural inflammation of any part of the gastrointestinal tract, while UC influences the mucosal layers of the colon and rectum. Its etiology includes complex interactions between the environment, heredity, microbes, and immunity. Genome-wide association studies have substantiated an increase in IBD susceptibility sites to 163, most of which are related to CD and UC, and most of them are implicated in regulating intestinal barrier function and host-microbe interactions. Recent researches in next-generation sequencing technology have affirmed adverse changes in the composition and function of the gut microbiota in IBD, including reduced gut microbiota diversity, reduced short chain fatty acids (SCFAs)-producing bacteria, and increased hemolytic bacteria, sulfate-reducing bacteria, and pathogenic bacteria. These variations can influence the integrity of the host′s immune system and barriers, causing chronic diseases and abnormal immune responses.FD is defined as a series of symptoms in the gastroduodenal region of the upper gastrointestinal tract and is described by one or more of the followings; postprandial fullness, early satiety, abdominal pain, epigastric burning, which are unexplained after a routine clinical examination. It includes two subgroups namely; postprandial distress syndrome, characterized by indigestion symptoms caused by meals, and epigastric pain syndrome, occurring not only after meals, and these two subgroups can overlap. The pathogenesis of FD is heterogeneous, and the association between possible pathophysiology factors is complex. Various alterations in the function and structure of the gastrointestinal tract in FD patients involves changes in the stomach such as impaired regulatory function, delayed gastric emptying and allergies, and changes in the duodenum like increased duodenal acid and/or lipid sensitivity and mild inflammation. These functional and structural abnormalities can interact, and other pathological mechanism incudes impaired mucosal integrity, barrier dysfunction, low-level immune activation, and abnormal regulation of the gut-brain axis.NAFLD is a common chronic liver disease, involving liver damage, from steatosis to steatohepatitis with or without fibrosis. Fibrosis may develop into cirrhosis and complications including hepatocellular carcinoma. It can be divided into non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) in histology. The development of NAFLD is associated related to obesity, hyperlipidemia, hypertension, type-2 diabetes and metabolic syndrome. Evidences suggest that elucidation of pathogenesis of NAFLD is still incomplete and is a result of a combination of various factors, including insulin resistance, oxidative stress, lipid metabolism alteration, inflammatory cytokines liberation, endoplasmic reticulum stress, gut dysbiosis or gut-liver axis activation, genetic and epigenetic factors. Few studies have demonstrated that the neurobehavioral disorder of NAFLD is associated with hyperammonemia, gut dysbiosis, metabolism and functional defects of brain regions. Plethora of evidence showed the microbiota-gut-live-brain axis plays an key regulatory role in the pathogenesis of NAFL/NASH, and the main contributors are the gut microbiota, its bacterial products, and the intestinal barrier.Cirrhosis is the end-stage of various chronic liver diseases, and is clinically typified by portal hypertension and decreased liver function. Among the various causes of cirrhosis, alcohol abuse and viral hepatitis are the most common. Decompensated cirrhosis can exhibit complications, such as jaundice, bleeding from varicose veins, ascites or HE. Bacterial translocation and its products such as endotoxin play an important role in the pathogenesis of HE, spontaneous bacterial peritonitis and other infections. The cirrhosis dysbiosis ratio can act as a useful quantitative indicator to ascertain the changes in the microbiome associated with the progression of cirrhosis. 

Source: Ding JH, Jin Z, Yang XX, et al. Role of gut microbiota via the gut-liver-brain axis in digestive diseases. World J Gastroenterol. 2020;26(40):6141-6162.