Prebiotic activity of lactulose optimizes gut metabolites and prevents systemic infection in liver disease patients

• DOI: 10.1101/2023.02.14.23285927
• Publication Date: 2023-02-16T18:15:20Z
• Authors: Matthew A. Odenwald; Huaiying Lin; Christopher Lehmann; Nicholas P. Dylla; Ramanujam Ramanswamy; Angelica Moran; Alan L. Hutchison; Matthew R. Stutz; Mark Dela Cruz; Emerald Adler; Jaye Boissiere; Maryam Khalid; Jackelyn Cantoral; Fidel Haro; Rita A. Oliveira; Emily Waligurski; Thomas G. Cotter; Samuel H. Light; Kathleen G. Beavis; Anitha Sundararajan; Ashley M. Sidebottom; K. Gautham Reddy; Sonali Paul; Anjana Pilliai; Helen S. Te; Mary E. Rinella; Michael R. Charlton; Eric G. Pamer; Andrew I. Aronsohn
• Keywords: Lactulose; Prebiotic; Liver disease; Hepatic Encephalopathy

ABSTRACT Progression of chronic liver diseases is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss critical hepatic functions, increasing morbidity risk infection. Medical interventions that treat complications failure, including antibiotic administration for systemic infections, impact gut microbiome composition metabolite production. Using a multi-omics approach on 850 fecal samples from 263 patients with acute or disease, we demonstrate hospitalized disease have reduced diversity paucity bioactive metabolites. We find treated orally administered but non-absorbable disaccharide lactulose increased densities intestinal Bifidobacteria incidence infections mortality. metabolize lactulose, produce high concentrations acetate acidify lumen, which, combination, can reduce growth antibiotic-resistant pathobionts such as Vancomycin-resistant Enterococcus faecium . Our studies suggest serve synbiotic to rates infection severe disease.