Roles for the mycobiome in liver disease

Abstract

Liver disease, a major cause of global mortality, has been associated with dysbiosis of the intestinal microbiota (bacteria, fungi, viruses, and other microbes). Studies have associated changes in gut bacteria with pathogenesis and severity of liver disease, but the contributions of the mycobiome (the fungal populations of the gut) to health and disease have not been well studied. We review recent findings of alterations in the composition of the mycobiota in patients with liver disease and discuss the mechanisms by which these might affect pathogenesis and disease progression. Strategies to manipulate the gut mycobiota might be developed to treat or prevent liver disease.

Could gut mycobiome play a role in NAFLD pathogenesis? Insights and therapeutic perspectives

“…Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease, affecting approximately 25% of the total adult population in Western countries. It is commonly associated with obesity and metabolic disorders such as dyslipidemia and insulin resistance, and it is considered as the hepatic manifestation of the metabolic syndrome [ 1 ]. The spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and even hepatocellular carcinoma (HCC).…”

“…A search in Medline identifies over 1400 studies on “NAFLD and microbiome” as opposed to around 10 studies on associations between “NAFLD and mycobiome”, indicating the recently emerging role of the mycobiome in the pathogenesis of NAFLD. The fungal community has been considered a minor component of the gut microbiota representing approximately less than 0.1% of the microbial community in the gut [ 1 ], while its role has been mainly studied in alcohol related liver disease [ 5 ]. Even though bacteria outnumber fungi in the gut, the biomass of fungal cells is important since they are almost 100-fold larger compared to bacteria.…”

“…They can use more complex biologic processes and produce metabolites that can remain in an organism and cause damage even after they have been eradicated. It is also noteworthy that fungal infections can be resistant to immune responses and difficult to eliminate especially in immunocompromised patients [ 1 ].…”

“…Antigens derived from the gut commensal fungi can cross the gastrointestinal barrier and be transported via the portal vein to the liver, thus having an impact on its function. The immune cells in the liver can contribute to the host homeostasis through immune responses to the intestinal fungi [ 1 ]. Thus, it has become apparent that gut mycobiome has a profound influence in modulating local as well as peripheral immune responses.…”

“…Th-17 cell mediated responses provide protection against fungi via the production of interleukin (IL)-17 and IL-22. The IL-17 receptor is expressed in almost all types of liver cells, implying that the antifungal immune response could lead to liver damage [ 1 ]. Interestingly, patients with an impairment in Th17 immunity mainly suffer from mucocutaneous candidiasis [ 12 ].…”