Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease?

Abstract

Changes in the intestinal microbiota composition contribute to the pathogenesis of many disorders including gastrointestinal and liver diseases. Recent studies have broadened our understanding of the “gut-liver” axis. Dietary changes, other environmental and genetic factors can lead to alterations in the microbiota. Dysbiosis can further disrupt the integrity of the intestinal barrier leading to pathological bacterial translocation and the initiation of an inflammatory response in the liver. In this article, the authors dissect the different steps involved in disease pathogenesis to further refine approaches for the medical management of liver diseases. The authors will specifically discuss the role of dysbiosis in inducing intestinal inflammation and increasing intestinal permeability.

Keywords:

• bacterial translocation
• gut-liver axis
• intestinal barrier
• intestinal inflammation
• metabolome
• metagenome
• microbiome

Financial & competing interests disclosure

The authors were supported in part by grants from the National Institute of Health (grant numbers: K08 DK081830, R01 AA020703, U01 AA021856) and by Award Number I01BX002213 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Changes in the microbiome are associated with liver disease.

• Several factors can contribute to changes in the microbiome including genetic factors, diet and other environmental factors.

• Change in the microbiome can lead to intestinal inflammation and contribute to gut barrier dysfunction.

• Once the intestinal barrier is disrupted, bacterial products can translocate and can enhance liver disease.

• The understanding of the microbiome–host interactions will help to develop patient-specific therapies for liver disease.