Abstract
Hepatic encephalopathy is a frequent and debilitating complication of liver disorders. Lactulose is an established and reasonably effective treatment, yet with incompletely understood mechanisms of action. The aims of this study were to examine how the faecal microbiota composition changed before, during and after lactulose treatment in a large animal model. Healthy, privately owned dogs (n = 18) completed a prospective cohort study. Faecal samples were collected weekly, while the subjects were either on their usual diet (week 1), or a standardised diet (weeks 2–9), with added oral lactulose in weeks 6–7. DNA extraction and 16S rRNA gene sequencing were undertaken. Faecal samples from week 7 had a significantly lower microbiota richness/diversity, based on observed operational taxonomic units, Shannon/Chao1 indexes and Pielou’s Evenness. Beta diversity based on UniFrac distances was significantly different in week 7 compared to weeks 1, 5 and 9. At the phylum level, week 7 was associated with a significant increase of Firmicutes and Actinobacteria, and a decrease of Bacteroidetes and Fusobacteria, when compared to weeks 5 and 9. In summary, we have shown that lactulose induces a reversible qualitative and quantitative change of the faecal microbiota, which may explain its clinical efficacy in the management of hepatic encephalopathy.
Highlights
Marisa da Fonseca Ferreira, Silke Salavati Schmitz, Jeffrey Joseph Schoenebeck, Dylan Neil Clements, Susan Mary Campbell, Donna Elaine Gaylor, Richard J
We have shown that lactulose induces a reversible qualitative and quantitative change of the faecal microbiota, which may explain its clinical efficacy in the management of hepatic encephalopathy
Side effects associated with lactulose administration included excessively soft faeces (n = 7) and unformed faeces (n = 1), all resolving after a dose reduction of 25% and 50%, respectively, not requiring a drop out from the study
Summary
Marisa da Fonseca Ferreira , Silke Salavati Schmitz, Jeffrey Joseph Schoenebeck , Dylan Neil Clements, Susan Mary Campbell, Donna Elaine Gaylor, Richard J. Lactulose is an established and reasonably effective treatment, yet with incompletely understood mechanisms of action. The aims of this study were to examine how the faecal microbiota composition changed before, during and after lactulose treatment in a large animal model. We have shown that lactulose induces a reversible qualitative and quantitative change of the faecal microbiota, which may explain its clinical efficacy in the management of hepatic encephalopathy. Hepatic encephalopathy (HE) is a frequent and debilitating neurological complication in patients with liver disease. A synthetic non-absorbable disaccharide, is a commonly used medication, with or without the addition of the antibiotic rifaximin, for both the treatment and prevention of HE, with a reasonable evidence of efficacy and added benefits in reducing morbidity and mortality[9,10].
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