The gut-liver axis is the communication between the intestine, its microbiome and the liver. Research into the relationship between the gut and liver is important for human health. Here we explore the connections between these two important organs.

How the liver and gut are connected

The liver and the intestine are anatomically linked. The liver gets most of its blood flow from the intestine. This blood flow enables the transport of nutrients from the food we eat to the liver.

The liver is the key metabolic organ of the body that produces and sends off metabolites to the whole body.

The liver’s letters to the gut – bile acids

Digestive fluids called bile acids are one element of the gut-liver axis.

Bile acids are small signaling molecules made in liver. The molecules move into the intestine. In the intestine, bile acids are important for absorbing fat.

Bile acids maintain the microbiome in the intestine. Some bile acids have antimicrobial properties which shape the community of microbes in the gut.

Gut microbes’ memos

Gut microbes change bile acids, and these transformed molecules return to the liver, where they stop the production of more bile acids. Around 95% of bile acids are recycled back to the liver in this process.

The gut microbiome affects the liver too when the microbial community is thrown out of balance in a process known as dysbiosis. This imbalance can cause the gut to become more leaky and microbial molecules to reach the liver. Even beneficial microbes that make up the microbiome can be harmful if they get into the bloodstream.

In the liver, the gut microbial molecules can cause inflammation and trigger progression of liver disease.

Liver disease

Liver disease describes a range of conditions when the liver no longer functions healthily.

Although liver disease can have different causes, the disease progresses in a similar way. There is increasing evidence of links between chronic liver disease and intestinal dysfunction.

Cholestasis is a stage of liver disease when the flow of bile from the liver to the small intestine is impaired and bile acid build-up destroys liver cells.

Research has shown mice without a microbiome are protected from liver damage by cholestasis. This suggests that  microbial molecules from the intestine reaching the liver are important in causing  liver damage.

Immune cells called macrophages appear to be important in communication between the gut and liver and affect how leaky the gut is. Researchers at the Quadram Institute are working to learn more about the mechanisms of the gut-liver axis in liver disease.

Liver regeneration

The liver is the only organ that can regenerate. Some of our researchers are understanding the role of the gut in liver regeneration and the role bile metabolism plays in this.

This work is important as transplants are currently the only option for those with chronic liver disease requiring surgery and immunosuppressants. Knowledge about the role of the gut in liver regeneration could lead to the development of new treatments. It could also help improve the outcome of transplantation, helping the liver to grow and reach the right size in the recipient of the transplant.

Role of diet in the gut-liver axis

There is some research that suggests bacteriotherapy such as prebiotics and probiotics could affect liver disease progression. But more studies are needed to translate this into a clinical practice.

Within the Quadram Institute, we are understanding the links between gut health, diet and the liver to reduce the impact and burden of liver disease.