A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.

Val‐Val‐Tyr‐Pro protects against non‐alcoholic steatohepatitis in mice by modulating the gut microbiota and gut‐liver axis activation

“…NASH is a more severe form of NAFLD, it encompasses a range of distinct pathological features in the liver, including hepatocellular ballooning, hepatocyte injury, liver inflammation, steatosis and fibrosis and can further progress to liver cirrhosis and HCC 37‐39 . Our previous study revealed that VVYP could reduce serum AST and ALT, improve the pathological state of liver tissue, and protect against liver injury caused by carbon tetrachloride or paracetamol in mice 33 .…”

Role and Mechanism of Gut Microbiota in Human Disease

“…The GM can also inhibit hepatic lipid synthesis by regulating BAs metabolism to alter FXR signaling pathways ( Iruzubieta et al, 2020 ). Studies have found that glycine may be directly related to the occurrence of NAFLD.…”

Gut Microbiota and Liver Interaction through Immune System Cross-Talk: A Comprehensive Review at the Time of the SARS-CoV-2 Pandemic

“…Who is responsible for this altered IP remains an open question in NAFLD physiopathology. An altered "dysmetabolic" gut microbiota could be the answer [76][77][78]. This obesogenic intestinal microbiota has been linked to the development of insulin resistance through the LPS/TLR4/CD14 systems [79].…”