Gut–liver axis, nutrition, and non-alcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called ”gut-liver axis”, play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host’s metabolism contributing to NAFLD development.

Innate Immunity and Inflammation in NAFLD/NASH

“…The concept of gut-liver axis [72–74] refers to the existence of a physiological crosstalk between the liver and intestine consisting of a myriad of signals evoking relevant immunological and metabolic effects in the target organ. In fact, bile secretion from the liver has important consequences beyond fat digestion.…”

“…Thus, if IB function is deranged, LPS and other bacterial-derived compounds increases in the portal blood leading to an increased activation of TLRs and other PRRs in the liver and triggering local inflammatory and fibrogenic responses. As mentioned earlier, activation of TLRs, particularly TLR-4 and TLR-9, by PAMPs seem to be a key phenomenon in liver injury amplification in NAFLD/NASH [35–37,72,74] as their signaling promotes disease progression in different experimental models. One issue that remains to be clarified is the potential existence of a hypersensitivity of NASH patients to LPS, which would explain inter-individual differences related to the extent of liver damage to a given endotoxemia level [74].…”

“…Several studies have shown that intestinal permeability is altered in subjects with NAFLD and that those with NASH exhibit a stronger association with altered intestinal permeability suggesting that liver injury and inflammation may be modulated by the degree of disruption of gut barrier integrity [72,78]. A recent meta-analysis of the existing literature showed that nearly 40% of patients with NAFLD had evidence of increased intestinal permeability compared with 6.8% of healthy individuals [79].…”

Fat Matters: Understanding the Role of Adipose Tissue in Health in HIV Infection

“…Drainage of microbial products to the liver may cause local inflammation, increased synthesis of triglycerides and fat droplet accumulation in hepatocytes, contributing to visceral adiposity [67, 68]. Additionally, both HIV infection and obesity are independently associated with gut microbiome alterations and increased intestinal permeability that further promote local and systemic inflammation [69-75]. Although a recent study demonstrated higher levels of monocyte activation and systemic inflammation in obese vs non-obese HIV-infected persons, additional research is needed to determine whether HIV and obesity have a synergistic effect on the burden of inflammation-related metabolic disease.…”

A bél–máj tengely vizsgálata colitis ulcerosában. Retrospektív tanulmány

“…A tápanyagok felszívódásáért és metabolizmusáért felelős kulcsszerveink a bél és a máj, amelyek a portalis áram-láson keresztül szoros kapcsolatban állnak egymással. A bélből felszívódó sokféle anyag (például: epesavak, tápanyagok, gyógyszerek, exogén és endogén toxinok) kerül be az enterohepaticus körforgásba, befolyásolva mindkét szerv működését [1][2][3][4][5].…”