Objective Cirrhotics have a high rate of infections, which are increasingly fungal or culture-negative in nature. While infected cirrhotics have bacterial dysbiosis, the role of fungi is unclear. We aimed to evaluate gut bacterial and fungal dysbiosis in cross-sectional and longitudinal analyses of outpatient and inpatient cirrhotics and prediction of hospitalisations.
Methods Cross-sectional: Age-matched controls, outpatients (with/without antibiotics) and hospitalised uninfected, culture-negative and culture-positive cirrhotics were included and followed for 90 days. Longitudinal: Three studies were conducted: (1) cirrhotics followed over 6 months, (2) outpatient cirrhotics administered antibiotics per standard of care for 5 days and (3) cirrhotics and controls administered omeprazole over 14 days. In all studies, stool bacterial/fungal profiles were analysed.
Results Cross-sectional: In 143 cirrhotics and 26 controls, bacterial and fungal diversities were significantly linked. Outpatients on antibiotics and patients with culture-positive infections had the lowest diversities. Bacterial and fungal correlations were complex in uninfected, outpatient and control groups but were markedly skewed in infected patients. 21% were admitted on 90-day follow-up. A lower Bacteroidetes/Ascomycota ratio was associated with lower hospitalisations. Longitudinal: Fungal and bacterial profiles were stable on follow-up (5 days and 6 months). After antibiotics, a significantly reduced bacterial and fungal diversity, higher Candida and lower autochthonous bacterial relative abundance were seen. After omeprazole, changes in bacterial diversity and composition were seen but fungal metrics remained stable.
Conclusion There is a significant fungal dysbiosis in cirrhosis, which changes differentially with antibiotics and proton pump inhibitor use, but is otherwise stable over time. A combined bacterial–fungal dysbiosis metric, Bacteroidetes/Ascomycota ratio, can independently predict 90-day hospitalisations in patients with cirrhosis.
Clinical trial number NCT01458990.
- ENTERIC BACTERIAL MICROFLORA
- INFECTIOUS DISEASE
- BACTERIAL INFECTION
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Contributors JSB conceptualised the study and was involved in all aspects. PMG was involved in the microbiota, bioinformatics and drafting and editing the paper. EJL, RK and MS were involved in microbiota and bioinformatics analysis. PH and DMH were involved in critical revision. MW, EAG and AF helped with subject enrolment.
Funding This work was partly supported by VA Merit Review CX10076 and McGuire Research Institute.
Competing interests No competing financial interest exists for any author.
Patient consent Obtained.
Ethics approval Virginia Commonwealth University and McGuire VAMC IRBs.
Provenance and peer review Not commissioned; externally peer reviewed.