Gut Microbiome and Organ Fibrosis

Abstract

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

Keywords: diet; gut microbiome; heart fibrosis; intestinal fibrosis; kidney fibrosis; liver fibrosis; lung fibrosis; therapeutic strategies.

Figure 1

Gut dysbiosis and organ fibrosis. TMAO, trimethylamine N-oxide; pCS, p-cresyl sulfate; IS, indoxyl sulfate; SCFAs, short-chain fatty acids; KEGG, Kyoto Encyclopedia of Genes and Genomes. ↑ increased; ↓ decreased; ≠ altered.