Microbiota and Gut–Liver Axis

Abstract

A specific bacterial gut microbiota profile with increased extraction of calories has recently been associated with obesity, which has been shown to be a transmissible phenotype by microbiota transplantation. At the same time, there is now increasing evidence that gut microbiota plays a role in the development of hepatic steatosis and its progression to non-alcoholic steatohepatitis, as well. This review summarizes well-known as well as unexpected interacting factors leading to obesity and its related hepatic diseases, including intestinal mucosal permeability and its regulation, gut microbiota and translocation of its biological products, and gut associated lymphoid tissue. These intestinal factors dictate also the balance between tolerance and immune response which are critical for most of the complications in near and far organs or systems. We will review novel mechanisms involving the development of gut permeability and adipose tissue plasticity, e.g. the crosstalk between the gut microbiota, lipopolysaccharide, high fat diet and the endocannabinoid system tone, which have hitherto not yet fully explored. Interactions between gut microbiota and other factors (e.g. inflammasome deficiency) will also be reviewed as emerging but far from being completely elucidated mechanisms influencing the onset of obesity and non-alcoholic fatty liver disease.

Innate Immunity and Inflammation in NAFLD/NASH

“…Structures of the IB include desmosomes, adherens junctions, and tight junctions that are formed by transmembrane proteins extracellularly interacting with neighboring cells and intracellularly bound to adaptor proteins linked to the cytoskeleton. The main components of tight junctions are zonulin-1, claudin, and occludin [73]. The IB is critical in controlling the pass of certain food-derived or bacterial products into the portal circulation.…”

Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism

“…Emerging findings in literature suggest a cross talk between the gut microbiota and liver (gut-liver axis) that impacts the development of metabolic syndrome, including obesity and fatty liver diseases (37). In this study, an integrative analysis demonstrated a strong correlation between gut microbiota and obesity-related metabolic pathways, such as lipid, glucose, and amino acid metabolism in the liver.…”

Shared Symptoms and Putative Biological Mechanisms in Chronic Liver Disease

“…Specialized intercellular structures known as tight junctions, along with PRRs, play a large role in regulating immune responses to bacteria and can prompt gut-associated lymphoid tissue when harmful bacteria is detected in the intestinal lumen (Miele et al, 2009; Vajro, Paolella, & Fasano, 2013). In CLD, the gut epithelium can lose its protective qualities due to injury of the tight junctions, which leads to intestinal barrier malfunction or leaky gut (Seki & Schnabl, 2012).…”

“…As a result, microbial translocation enhances liver inflammation, thus further compromising liver function and contributing to fibrosis (Seki & Schnabl, 2012). Increased barrier permeability can allow bacteria, fungi, parasites, and their toxins to move from the intestinal lumen to the submucosa and bloodstream (Vajro et al, 2013). Ultimately, a disruption of the homeostasis between the gut microbiome and the immune system increases an individual’s disease risk and may alter neurocognitive function (Quigley & Mansour, 2013).…”

“…These changes can alter the production of short-chain fatty acids and peptidoglycan, which have immune modulatory and regulatory functions, thereby altering the communication between the immune system and brain. Future research should exploit the ability of the microbiota to influence the CLD symptom cluster as well as repair and remodeling of the liver–gut–brain axis (Vajro et al, 2013). …”