Gut fungal dysbiosis: what role in cirrhosis?

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The gut mycobiota is believed to be involved in the development of cirrhosis and its complications, and as such should be considered when making therapeutic choices. A bacteria/fungi ratio could even be used as a predictor for the risk of hospitalization.

 

As their immune system is weakened, cirrhotic patients are at a higher risk of infections typically caused by bacteria. The intensive use of antibiotics and proton pump inhibitors (PPIs) in those patients results in significant increases in the number of infection cases of unknown (culture-negative) or fungal origin. This is what prompted an American team to characterize fungal and bacterial dysbiosis and find patterns in the bacteria/fungi ratio depending on the health status of cirrhotic patients, with the ultimate goal of being able to predict the risk of hospitalization.

Parallel progression of cirrhosis and dysbiosis

In a first study, 26 control subjects and 143 cirrhotic subjects were monitored for 90 days: 77 in outpatient care and 66 in hospital care, including 47 (25 culture-positive, 22 culture-negative) with an infection treated with antibiotics. The analysis revealed that the bacterial and fungal diversities of the fecal microbiota (lower in non-hospitalized patients treated with antibiotics, and even lower in hospitalized subjects) were significantly linked and that this correlation was strongly reduced in case of infection. In addition, dysbiosis increases as the clinical condition gradually worsens until end-stage liver disease.

Bacteria/fungi ratio as a predictor of hospitalization

A cross-sectional analysis highlighted that a low Bacteroidetes/Ascomycota ratio was associated with a lower risk of hospitalization at 90 days, regardless of the severity of cirrhosis, the presence of hepatic encephalopathy and the available clinical biomarkers. This metric combining bacterial microbiome and mycobiome could be used as a predictive tool. Three other studies performed in parallel with control subjects and cirrhotic patients receiving or not antibiotics or IPPs, yielded the following results: firstly, the gut bacterial and fungal profiles remain stable over time. Secondly, antibiotic treatments alter both the diversity and composition of these two microbiotas. Lastly, while the use of IPPs has little impact on the mycobiota, it does affect microbial diversity.

The gut mycobiota as a potential therapeutic tool

All these results demonstrate that fungi can play an important role as modulators of general gut dysbiosis and should be considered in prophylactic and therapeutic decisions in cirrhotic patients. They also call for further research into whether a reduced relative abundance of Ascomycota could prevent the development of fungal infections and hospitalization.

 

Sources:

J. Bajaj, E. Liu, R. Kheradman, et al. Fungal dysbiosis in cirrhosis. Gut, published online June 3, 2017 ; doi:10.1136/gutjnl-2016-313170