The gut microbiota-A vehicle for the prevention and treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) arises principally against a background of cirrhosis and these two diseases are responsible globally for over 2 million deaths a year. There are few treatment options for liver cirrhosis and HCC, so it is vital to arrest these pathologies early in their development. To do so, we propose dietary and therapeutic solutions that involve the gut microbiota and its consequences. Integrated dietary, environmental and intrinsic signals result in a bidirectional connection between the liver and the gut with its microbiota, known as the gut -liver axis. Numerous lifestyle factors can result in dysbiosis with a change in the functional composition and metabolic activity of the microbiota. A panoply of metabolites can be produced by the microbiota, including ethanol, secondary bile acids, trimethylamine, indole, quinolone, phenazine and their derivatives and the quorum sensor acyl homoserine lactones that may contribute to HCC but have yet to be fully investigated. Gram-negative bacteria can activate the pattern recognition receptor toll-like receptor 4 (TLR4) in the liver leading to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling, which can contribute to HCC initiation and progression. The goal in preventing HCC should be to ensure a healthy gut microbiota using probiotic supplements containing beneficial bacteria and prebiotic plant fibers such as oligosaccharides that stimulate their growth. The clinical development of TLR4 antagonists is urgently needed to counteract the pathological effects of dysbiosis on the liver and other organs. Further nutrigenomic studies are required to understand better how the diet influences the gut microbiota and its adverse effects on the liver.

Automated summary

Hepatocellular carcinoma (HCC) is a major complication of liver cirrhosis, causing over 2 million deaths globally each year. There are limited treatment options for liver cirrhosis and HCC, emphasizing the importance of early intervention. This article proposes dietary and therapeutic solutions that involve the gut microbiota and its consequences. Dysbiosis, the imbalance of gut microbiota, can be induced by various lifestyle factors and produce metabolites that may contribute to HCC development. The activation of toll-like receptor 4 (TLR4) by gram-negative bacteria in the liver can also contribute to HCC initiation and progression. To prevent HCC, maintaining a healthy gut microbiota through the use of probiotic supplements and prebiotic plant fibers is suggested. Additionally, the development of TLR4 antagonists and further nutrigenomic studies are deemed urgent to counteract dysbiosis and understand the effects of diet on the gut microbiota and liver.