Dysbiosis in the gut microbiome can cause the progression of chronic liver diseases via the gut-liver axis, according to the authors of a literature review published in Seminars in Immunology. The authors note that while this research provides novel insights that can lead to new treatment options, there are still obstacles preventing clinical solutions.¹

“[Obstacles] include the lack of a regulatory road map for microbiome based or -targeted therapies, insufficient global agreements on definitions, standardization on sampling, [and] handling and analyzing bacterial consortia, [which can hinder] comparison between studies,” study authors wrote.

More than 2 million people die from chronic liver diseases every year. A growing body of literature supports the gut’s involvement with the liver, among other key organs like the brain, kidneys, heart, lungs, and muscles.¹ The gut communicates with the liver through the gut-liver axis, which encompasses the relationship between the gut, gut microbiota, and liver.^1,2

The aim of this review is to evaluate the pathophysiological role of the gut-liver axis on triggering or worsening liver diseases. Investigators first identified a series of complex and diverse stimuli in the microbiota that activate this gut-liver axis. These include microbe-associated molecular patterns, pathogen-associated molecular patterns gut-derived metabolites, and hormones.¹

The microbiota could be pathophysiological because the gut-liver-organ (liver, stomach, small and large intestine) are supplied blood that drains gut-derived substances into the liver. These substances are also drained into the liver via the lymphatic system, and “it is tempting to speculate that the “gut-liver”-organ may well represent the largest source of stimuli for internal, nuclear, as well as cell-surface receptors of any kind within the human body,” study authors wrote.

There is also research which suggests that bile can facilitate pathological communication between the liver and gut, especially if there is permeability in the intestines, or if the bile undergoes enterohepatic circulation. Bile acid can also reduce gut microbial diversity, leading to pathophysiology in the gut-liver axis; certain types of toxic bile acid (secondary bile acid) which enter the liver can cause inflammation and lead to the development of cancer.

Additionally, it’s been show that intestinal permeability—which is also termed “leaky gut”—may challenge the liver by promoting bacterial translocation. Translocation can occur when the microbiome is disrupted (which can lead to bacterial overgrowth and/or dysbiosis), when the gut mucosal barrier is disrupted, or when lymphatic tissue in the gut is not defending the body properly.

There are other pathologies that may contribute to liver-gut axis dysbiosis, which can also include diet and intestinal epithelial cells. Investigators suggest that some of the best ways to improve liver outcomes (and the liver-gut axis) include individualizing treatment of the microbiome. This can relate to more targeted approaches to the anti-inflammatory diet, pre- and probiotics, fecal microbiota transplant, and precision medicine.

“[This] does require a better characterization and phenotyping of each patient in terms of microbiome (composition at the strain-level and functionality assessed by metagenomic analysis at best in luminal, mucus and mucosa-compartment), metabolome and particularly host response,” wrote the study authors.

REFERENCES

1. Rodrigues SG, van der Merwe S, Krad A, Wiest R. Gut-liver axis: Pathophysiological concepts and medical perspective in chronic liver diseases. Sem in Immun. 2024(71); e101859. doi:10.1016/j.smim.2023.1018592. Albillos A, de Gottardi A, Rescigno M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol. 2020 Mar;72(3):558-577. doi:10.1016/j.jhep.2019.10.003.