Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Autor: Odenwald MA; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA. matthew.odenwald@uchicagomedicine.org., Lin H; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Lehmann C; Department of Medicine, Section of Infectious Diseases and Global Health, University of Chicago, Chicago, IL, USA., Dylla NP; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Cole CG; Duchossois Family Institute, University of Chicago, Chicago, IL, USA.; Department of Microbiology, University of Chicago, Chicago, IL, USA., Mostad JD; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Pappas TE; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Ramaswamy R; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Moran A; Department of Pathology, University of Chicago, Chicago, IL, USA., Hutchison AL; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA., Stutz MR; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cook County Health, Chicago, IL, USA., Dela Cruz M; Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL, USA., Adler E; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Boissiere J; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Khalid M; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Cantoral J; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Haro F; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Oliveira RA; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Waligurski E; Duchossois Family Institute, University of Chicago, Chicago, IL, USA.; Department of Microbiology, University of Chicago, Chicago, IL, USA., Cotter TG; Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA., Light SH; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Beavis KG; Department of Pathology, University of Chicago, Chicago, IL, USA., Sundararajan A; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Sidebottom AM; Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Reddy KG; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA., Paul S; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA., Pillai A; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA., Te HS; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA., Rinella ME; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA., Charlton MR; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA., Pamer EG; Duchossois Family Institute, University of Chicago, Chicago, IL, USA. egpamer@bsd.uchicago.edu.; Department of Medicine, Section of Infectious Diseases and Global Health, University of Chicago, Chicago, IL, USA. egpamer@bsd.uchicago.edu.; Department of Microbiology, University of Chicago, Chicago, IL, USA. egpamer@bsd.uchicago.edu., Aronsohn AI; Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2023 Nov; Vol. 8 (11), pp. 2033-2049. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1038/s41564-023-01493-w
Abstrakt: Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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