Increased small intestinal permeability in chronic liver disease is associated with reduced abundance of Faecalibacterium prausnitzii in the terminal ileum mucosa

Abstract

Background and Aims: Chronic liver disease (CLD) is associated with dysbiosis of the stool microbiota, but little is known about the mucosal microbiota of the terminal ileum, some of which may be beneficial for mucosal integrity. Our aim was to evaluate for dysbiosis of the terminal ileum mucosal microbiota and identify associations with small intestinal permeability and disease severity in subjects with CLD. Methods: Subjects with and without CLD, undergoing routine colonoscopy for polyp surveillance or iron deficiency anaemia, were prospectively recruited. Those with mucosal inflammation or functional bowel disease were excluded. Bacterial DNA was sequenced (Illumina® Miseq) from mucosal biopsies taken from the terminal ileum. Small intestinal permeability was assessed by the plasma ratio of lactulose:rhamnose (L:R) following oral administration, and hepatic fibrosis estimated by Transient Elastography. The presence of the Metabolic syndrome was assessed by the IDF/AHA/NHLBI 2009 consensus criteria. Statistical analysis was performed by SPSS v22 and Calypso version 5.2. Results: 21 subjects with CLD (Male:Female;15:6; age 40-76 yrs) and 25 controls (M:F; 13:12; age 36-73 yrs ) were assessed. As a community, the microbial composition of terminal ileal microbiota in CLD was similar to controls, with no significant separation between the groups on redundancy analysis (p = 0.71), and similar microbial diversity (Shannon index, p = 0.68). However, in CLD subjects there was a strong inverse correlation between small intestinal permeability and the relative abundance of Faecalibacterium prausnitzii (r = -0.79, p = 0.015, corrected for multiple comparisons, Figure 1), which was not seen in the controls. There was no association between hepatic fibrosis or the Metabolic syndrome and terminal ileum microbiota in CLD (p > 0.05). Conclusion: Faecalibacterium prausnitzii, a commensal bacteria with anti-inflammatory effects, has a role in maintaining gut mucosal integrity. In CLD, reduced abundance of Faecalibacterium prausnitzii in the terminal ileum mucosa may be implicated in the pathogenesis of increased small intestinal permeability.