Source

1Virginia Commonwealth University and McGuire VAMC.

Abstract

Although hepatic encephalopathy (HE) is linked to the gut microbiota, stool microbiome analysis has not found differences between HE and no-HE patients. Aim: to compare sigmoid mucosal microbiome of cirrhotics to controls, between HE to no-HE patients and to study their linkage with cognition and inflammation. Methods: Sixty cirrhotics[36 HE/24 no-HE]) underwent cognitive testing, stool collection, cytokine (Th1, Th2, Th17 and innate immunity) and endotoxin analysis. 36 patients(19 HE and 17 no-HE) and 17 age-matched controls underwent sigmoid biopsies. Multi-tag pyrosequencing (including autochthonous genera, i.e.,Blautia,Roseburia,Fecalibacterium,Dorea) was performed on stool and mucosa. Stool and mucosal microbiome differences within/between groups and correlation network analyses were performed. Results: Controls had significantly higher autochthonous and lower pathogenic genera compared to cirrhotics, especially HE patients. HE patients had worse MELD, cognition, higher IL-6 and endotoxin than no-HE. Mucosal microbiota was different from stool within both HE/no-HE groups. Between HE/no-HE patients, there was no difference in stool microbiota but mucosal microbiome was different with lower Roseburia and higher Enterococcus, Veillonella, Megasphaera and Burkholderia abundance in HE. On network analysis, autochthonous genera (Blautia, Fecalibacterium, Roseburia and Dorea) were associated with good cognition and decreased inflammation in both HE/no-HE, while genera over-represented in HE (Enterococcus, Megasphaera and Burkholderia) were linked to poor cognition and inflammation. Conclusion: Sigmoid mucosal microbiome differs significantly from stool microbiome in cirrhosis. Cirrhotic, especially HE patients' mucosal microbiota is significantly different from controls with a lack of potentially beneficial autochthonous and overgrowth of potentially pathogenic genera, which are associated with poor cognition and inflammation.