Abstract
Diabetes (DM) is prevalent in cirrhosis and may modulate the risk of hospitalization through gut dysbiosis. We aimed to define the role of gut microbiota on 90-day hospitalizations and of concomitant DM on microbiota. Cirrhotic outpatients with/without DM underwent stool and sigmoid mucosal microbial analysis and were followed for 90 days. Microbial composition was compared between those with/without DM, and those who were hospitalized/not. Regression/ROC analyses for hospitalizations were performed using clinical and microbial features. 278 cirrhotics [39% hepatic encephalopathy (HE), 31%DM] underwent stool while 72 underwent mucosal analyses. Ultimately, 94 were hospitalized and they had higher MELD, proton pump inhibitor (PPI) use and HE without difference in DM. Stool/mucosal microbiota were significantly altered in those who were hospitalized (UNIFRAC p< = 1.0e-02). Specifically, lower stool Bacteroidaceae, Clostridiales XIV, Lachnospiraceae, Ruminococcacae and higher Enterococcaceae and Enterobacteriaceae were seen in hospitalized patients. Concomitant DM impacted microbiota UNIFRAC (stool, p = 0.003, mucosa,p = 0.04) with higher stool Bacteroidaceae and lower Ruminococcaeae. Stool Bacteroidaceaeae and Clostridiales XIV predicted 90-day hospitalizations independent of clinical predictors (MELD, HE, PPI). Stool and colonic mucosal microbiome are altered in cirrhotics who get hospitalized with independent prediction using stool Bacteroidaceae and Clostridiales XIV. Concomitant DM distinctly impacts gut microbiota without affecting hospitalizations.
Highlights
Hospitalizations in cirrhosis are associated with susceptibility to nosocomial and second infections and can predict a poor prognosis[1]
On metastats and Kruskal-Wallis tests specific microbial families were significantly different in cirrhotics who developed a 90-day hospitalization compared to the rest (Table 3, Figure S1)
We found that cirrhotic subjects who required non-elective 90-day hospitalization had a different microbial profile that could add to the current models for this prediction
Summary
Hospitalizations in cirrhosis are associated with susceptibility to nosocomial and second infections and can predict a poor prognosis[1]. Type 2 diabetes mellitus (DM) is frequently found in patients with cirrhosis, especially with non-alcoholic steatohepatitis (NASH) and hepatitis C infection, which could worsen the prognosis[2,3,4] These hospitalizations, which are most commonly liver-related, could be due to a systemic pro-inflammatory milieu brought on by gut dysbiosis[5,6,7]. Given the presence of concomitant DM in a large proportion of cirrhotic patients[3,4], it is relevant to its additive impact on the gut microbiota composition and 90-day hospitalizations in cirrhosis This is partly because DM in non-cirrhotic settings can profoundly impact the gut microbiota with and without the presence of obesity[9,10]. The aim of our study was to (i) evaluate the role of gut microbiota in independently predicting 90-day hospitalizations in cirrhosis and (ii) evaluate the impact of DM on this risk through its impact on the gut microbiota
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