Altered Microbiota in Cirrhosis and Its Relationship to the Development of Infection
Patients with cirrhosis are predisposed to infections, which often have a very poor prognosis.1 Most of this poor prognosis stems from the development of end-stage organ diseases and nosocomial infections that result in acute-on-chronic liver failure (ACLF).2 Infections are one of the most common precipitants of ACLF in Western countries.2 Once this organ failure cycle sets in, it is difficult to reverse, which is why we need to determine prognostic markers that predict the early development of infections and subsequent ACLF. A large proportion of infections in cirrhosis are related to gut barrier changes such as spontaneous bacterial peritonitis (SBP), and gut microbiota could be a relevant focus of study.3, 4
Gut Microbiota Changes in Cirrhosis
Patients with cirrhosis have an altered gut-liver axis related to changes in liver disease severity, gut barrier impairment, and intestinal and systemic inflammation that are associated with changes in gut microbiota composition and function. Cirrhosis is associated with an altered immune response that potentially allows for dysbiosis or an altered microbiota in the stool, intestinal mucosa, ascites, liver, serum, and saliva.5 In the gut specifically, there is an increased relative abundance of bacterial taxa belonging to Enterobacteriaceae (includes gram-negative rods such as Escherichia coli and Klebsiella), Enterococcaceae (includes Enterococcus faecalis and E. faecium), Streptococcaceae, and lower potentially beneficial taxa such as Lachnospiraceae and Ruminococcaceae in advancing cirrhosis.3, 6 In addition to these changes in microbial composition, there are also changes in bacterial function, including higher endotoxin, lower conversion from primary to secondary bile acids, and reduced short-chain fatty acids. These changes in cirrhosis can have real-world consequences.7
Gut Microbiota Changes and Clinical Consequences in Outpatients With Cirrhosis
In outpatients with cirrhosis, there are several outcomes of interest such as hospitalizations, cognitive dysfunction, and hepatic encephalopathy (HE). Studies on stool and colonic mucosal and salivary microbiota are associated with 90-day hospitalizations in cirrhosis independent of clinical covariates.7 This is similar regardless of whether the DNA or RNA content of the stool was used. Stool and colonic mucosal microbiota are also linked with brain function on cognitive tests and magnetic resonance imaging, with oral-origin microbiota such as Porphyromonadaceae associated with neuronal and Enterobacteriaceae, Lachnospiraceae, and Ruminococcaceae with astrocytic changes.8
Gut Microbiota Changes in Inpatients With Infection With Cirrhosis
The cirrhosis/dysbiosis ratio (CDR) was created to simplify the enormous complexity of gut microbiota. CDR is the ratio of potentially beneficial bacteria (Lachnospiraceae + Ruminococcaceae + Clostridium Cluster XIV + Veillonellaceae) in the numerator and potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) as the denominator.3 Therefore, a high ratio indicates healthy microbiota. As shown in Fig. 1, the best CDR was in controls and the worst/lowest one was in inpatients with infection, the majority of whom had gut-associated infections such as SBP. This ratio also had prognostic value and was stable in clinically stable patients over time.
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