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Understanding the gut-liver axis: implications for NAFLD prevention and treatment

You may have heard; humans are superorganisms. The human large intestine harbors tens of trillions of microbes, which equates to roughly 2 kg of cells. For reference, that’s how much your brain weighs! Within the gut microbiome, it is estimated that there are over 1,000 different species of bacteria.

These bacteria can do all kinds of things – fermenting the indigestible food that you eat, producing a myriad of metabolites, and communicating with all parts of the host (you!).

Understanding how the gut microbiome is talking to different organs, or tissues, in the host is becoming an important component of understanding host health outcomes, disease states, and life as we know it.

Specifically, research has shown that bacteria in the large intestine are able to communicate with the liver via portal circulation. These bacteria produce a variety of metabolites that can travel to the liver and be used for energy or as signaling and regulatory molecules.

This crosstalk has implications for preventing and treating liver diseases, such as non-alcoholic fatty liver disease (NAFLD).

The gut microbiome and NAFLD

Non-alcoholic fatty liver disease (NAFLD) afflicts approximately 25% of the global population and is considered a silent disease. This means that many people do not have any symptoms of the disease and are only diagnosed or treated once it progresses to late stages.

At this time, the only treatment is weight loss, whether by surgical measures or dietary and lifestyle interventions. Establishing other methods of prevention and treatment for the early stages of this disease is needed.

This is where the gut microbiome comes in.

Through my research, I have found that a novel prebiotic dietary fiber is able to dramatically shift the populations in the gut microbiome and prevent fatty liver in rats fed high-fat diets.

This indicates that specific microbiome landscapes are important for the etiology of NAFLD and can be manipulated for therapeutics.

Continuing this research lineage will provide novel insights into, i) how we can manipulate the gut microbiome to reduce fatty liver and ii) how the gut microbiome is able to bridge the gut-liver axis in order to modify lipid metabolism.

Crosstalk between the gut and the liver

There are many pathways that can be involved.

The bacteria in the gut are able to utilize undigested matter (such as dietary fibers and certain phytochemicals) for their own sustenance, thereby producing or excreting other molecules that the host can use. One heavily studied class of molecules are short chain fatty acids (SCFAs).

These SCFAs are fermentation products that can be used by certain cells in the body for energy metabolism, metabolic regulation, and cell signaling.

Specifically, acetate and propionate (two prominent SCFAs) from the gut microbiome have been shown to regulate lipid metabolism in the liver. This is one potential key mechanism of crosstalk between the gut and the liver that can reduce fatty liver.

Another potential regulatory mechanism is through lipopolysaccharide (LPS). LPS is excreted by certain types of bacteria and be taken up into portal circulation by the host. This can lead to increased production of inflammatory cytokines released by tissues such as the adipose, promoting downstream complications in other tissues, such as the liver.

These are just two examples of ways that we know the gut microbiome can communicate with other tissues, such as the liver, to promote or prevent disease.

Upon further investigation into these mechanisms and others, we can better understand how NAFLD works, allowing us to establish novel therapeutics for the prevention and treatment of the disease through manipulation of the gut microbiome.

Breann Abernathy is a 5th year PhD candidate in nutritional biochemistry and molecular biology at the University of Minnesota, US. Her research focuses on how the gut microbiome communicates with the liver in order to prevent hepatic lipid accumulation.

Join hundreds of other leaders in the global microbiome community to explore novel therapeutic applications at the 7th Microbiome and Probiotics R&D and Business Collaboration Forum. Read the agenda.

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