Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease

Abstract

Fructose is one of the key dietary catalysts in the development of non-alcoholic fatty liver disease (NAFLD). NAFLD comprises a complex disease spectrum, including steatosis (fatty liver), non-alcoholic steatohepatitis, hepatocyte injury, inflammation, and fibrosis. It is also the hepatic manifestation of the metabolic syndrome, which covers abdominal obesity, insulin resistance, dyslipidemia, glucose intolerance, or type 2 diabetes mellitus. Commensal bacteria modulate the host immune system, protect against exogenous pathogens, and are gatekeepers in intestinal barrier function and maturation. Dysbalanced intestinal microbiota composition influences a variety of NAFLD-associated clinical conditions. Conversely, nutritional supplementation with probiotics and preobiotics impacting composition of gut microbiota can improve the outcome of NAFLD. In crosstalk with the host immune system, the gut microbiota is able to modulate inflammation, insulin resistance, and intestinal permeability. Moreover, the composition of microbiota of an individual is a kind of fingerprint highly influenced by diet. In addition, not only the microbiota itself but also its metabolites influence the metabolism and host immune system. The gut microbiota can produce vitamins and a variety of nutrients including short-chain fatty acids. Holding a healthy balance of the microbiota is therefore highly important. In the present review, we discuss the impact of long-term intake of fructose on the composition of the intestinal microbiota and its biological consequences in regard to liver homeostasis and disease. In particular, we will refer about fructose-induced alterations of the tight junction proteins affecting the gut permeability, leading to the translocation of bacteria and bacterial endotoxins into the blood circulation.

Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress

“…The suggested role of AMPK as an important energy sensor linking fructose metabolism to the regulation of inflammatory signaling is further supported by recent findings of Cao et al [60], showing that fructose amplifies inflammatory potential in human monocytic cells via a reduction of AMPK activity. However, high fructose concentrations in the liquid form can affect gut permeability, leading to the leakage of bacteria and their endotoxins into the circulation [61]. Therefore, metabolic effects of fructose on hepatic inflammation may not be direct but then conducted through the toxic effects of bacterial products on the liver cells, especially through activation of TLR4 [62] and NLRP3 inflammasome [63].…”

Machine learning reveals missing edges and putative interaction mechanisms in microbial ecosystem networks

“…D-Fructose was the most commonly found metabolite, accounting for ∼18.7% of all discovered metabolites. Interestingly, fructose has been shown to be implicated in altering the gut microbiome in connection to a number of diseases, including antibiotic treatable (22) metabolic syndrome (23, 24), liver disease (25), and obesity (26).…”

Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

“…Because fructose metabolism is 90% hepatic, these changes in D-lactate mirror other changes in liver metabolism. However, D-lactate also may be produced from intestinal microbiota, and fructose may change the flora (35). Thus, changes in D-lactate levels after fructose restriction may not solely reflect liver metabolism; however, it would be difficult to explain the correlations with DNL, liver fat, and triglycerides if serum D-lactate was coming from the gut.…”