Consequences of lifestyle issues across the UK, including alcohol consumption, obesity and the associated dietary patterns like high sugar, high saturated fat and low fibre intake, are of particular concern with regards to liver health1. This blog will discuss how dietary factors and the gut microbiome fit into this.

Declining liver health is a major cause for implementing public health interventions worldwide, and an aberrant gut microbiota may be a factor in the development of liver disease2. The gut is involved in the pathogenesis of hepatic fat deposition, the leading cause of chronic liver conditions around the world3. The gut-liver axis refers to the bidirectional relationship between the gut, the gut microbiome and the liver. The interaction between the gut microbiome and the liver is through the portal vein, carrying products of digestion and bacterial fermentation to the liver and the supply of bile (and immune compounds) from the liver to the intestine4.

Liver health and the gut microbiome

The gut microbiome, the community and composition of bacteria in the gut that influences key areas of physical and mental health, has the ability to produce a diverse range of compounds through the metabolism of food or the metabolism of by-products of cholesterol synthesis in the liver5. Bile acids are synthesised in the liver from cholesterol to support the absorption of lipids in digestion and can regulate gut microbiome composition. When liver health declines, low concentrations of bile acids entering the intestine are related to changes to bacterial composition in the gut microbiome and increases in toxic metabolites. High levels of bile acids from dietary causes or genetics may be detrimental to the composition of the gut microbiome, increasing toxic secondary bile acids6. The relevance of bile acids to the gut microbiome, and vice-versa, demonstrates the bidirectional impact of the gut-liver axis.

Alcohol

Increased gut permeability is a main characteristic of alcohol-related liver conditions due to the toxic effect of alcohol on the epithelial cells and tight junctions in the gastrointestinal tract. The disruption to the gut barrier exposes the liver to hepatic injury due to the elevated plasma levels of endotoxins. The composition of the gut microbiota may also be responsible for a decline in liver health and reducing dysbiosis to improve gut-barrier function may improve management of liver health2.

Lifestyle and the liver

The gut microbiome is the first interface between the environment and almost all the metabolic, biochemical, endocrine, and signalling pathways influencing liver function3. Dietary habits can influence the microbiota, the intestinal permeability, and the vascular barrier. This can lead to the enhanced influx of endotoxins in the portal vein and low-grade liver inflammation7. Dietary intake of carotenoids, Vitamin E and omega 3s holds potential for liver health due to their antioxidant capacity. Carotenoids are found mostly in fruits and vegetables and help to reduce lipid deposition and inflammation in the liver8.

Accumulation of fat in the liver occurs due to an imbalance between lipid deposition and lipid removal from hepatic synthesis of triglycerides and de novo lipogenesis. An unhealthy diet, excess energy intake and sedentary behaviour are the main drivers of excess lipid deposition with gene-behaviour interactions. Obesity and low physical activity levels effect triglyceride (TGs) turnover. TGs are related to deposition of fat in the liver; therefore, sedentariness and low levels of physical activity or exercise can increase the risk of fat deposition9.

The Mediterranean Diet (MedDiet) has been proven beneficial for health due to its strength of phytochemicals and ability to modulate the gut microbiome. The addition of antioxidants to the diet can reduce risk of metabolic syndrome and its manifestations. The MedDiet not only improves liver health on a clinical level, but there are improvements to inflammatory biomarkers, such as cytokines, involved in immune response. Furthermore, probiotics alongside a MedDiet and physical activity appear to be beneficial for liver health. Lactobacillus in particular is beneficial for liver health, but their action is supported by the fermentation of prebiotics, plant fibres and polyphenols in a MedDiet10. In contrast, typical elements of a Western diet such as high fructose corn sugars used in Ultra-processed foods (UPFs) and drinks, commonly used to sweeten beverages and other UPFs, are linked to fat deposition in the liver9 when consumed in excessive quantities.

Mediterranean Food

Probiotics and prebiotics for liver health

Probiotics are live microorganisms that, when administered in adequate quantities, confer a benefit to the host. Probiotics are reported to repair the gut barrier function and reduce inflammation associated with the gut microbiome. In turn, the gut barrier function and reduced inflammation leads to reduced liver TGs11. Furthermore, synbiotics (combining prebiotics and probiotics) that include bifidobacteria show improvements in serum metabolic, inflammatory markers and liver enzymes. Different probiotic strains have varied roles in the gut-liver axis such as reducing gut permeability, modulating the liver inflammatory pathway or translocation of bacterial products in portal circulation11.

Prebiotics affect the gut barrier and have been shown to reduce liver inflammation, but more research is needed to determine if this is correlated with gut microbiome changes12. Prebiotic and probiotic interventions, varying between 8 and 30 weeks, lead to a reduction in liver damage markers and insulin resistance of which may be clinically relevant in some circumstances. In combination, the research on prebiotics, probiotics and synbiotics to support the gut-liver axis, shows a great deal of promise. However, further interventions are required to determine the beneficial effects with more accuracy. Furthermore, it is confirmed that there are no adverse side-effects from prebiotics, probiotics and synbiotics for the gut-liver axis13.

In conclusion, there is a strong case for further study into interventions using dietary influence on the gut microbiome to benefit the gut-liver axis. The gut microbiome and liver are closely linked in metabolic function, but mechanisms for the gut-liver axis influence on health need more research.

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