The Mucosally-Adherent Rectal Microbiota Contains Features Unique to Alcohol-Related Cirrhosis

Most studies examining correlations between the gut microbiota and disease states focus on fecal samples due to ease of collection, yet there are distinct differences when compared to samples collected from the colonic mucosa. Although fecal microbiota has been reported to be altered in cirrhosis, correlation with mucosal microbiota characterized via rectal swab has not been previously described in this patient population. We conducted a cross-sectional analysis using 39 stool and 39 rectal swabs from adult patients with cirrhosis of different etiologies and performed shotgun metagenomic sequencing. Bacterial growth studies were performed with Escherichia coli. Two asaccharolytic bacterial taxa, Finegoldia magna and Porphyromonas asaccharolytica, were increased in rectal swabs relative to stool (FDR < 0.01). Genomic analysis of the microbiome revealed 58 genes and 16 pathways that differed between stool and rectal swabs (FDR < 0.05), where rectal swabs were enriched for pathways associated with protein synthesis and cellular proliferation but decreased in carbohydrate metabolism. Although no features in the fecal microbiome differentiated cirrhosis etiologies, the mucosal microbiome revealed decreased abundances of E. coli and Enterobacteriaceae in alcohol-related cirrhosis relative to non-alcohol related cirrhosis (FDR < 0.05). In vitro bacterial culture studies showed that physiological concentrations of ethanol and its oxidative metabolites inhibited E. coli growth in a pH- and concentration-dependent manner. Characterization of the mucosally associated gut microbiome via rectal swab revealed findings consistent with amino acid/nitrogen abundance versus carbohydrate limitation in the mucosal microenvironment as well as unique features of alcohol-related cirrhosis possibly consistent with the influence of host-derived metabolites on the composition of mucosally adherent microbiota.