Faecal bacterial microbiota in patients with cirrhosis and the effect of lactulose administration

Abstract

BackgroundGut microbiota may be altered in patients with cirrhosis, and may further change after administration of lactulose. We studied the composition of gut microbiota in patients with cirrhosis and assessed the effect on it of lactulose administration.MethodsStool specimens were collected from 35 patients with cirrhosis (male 26; median [range] age: 42 [29–65] years) and 18 healthy controls (male 14; 44.5 [24–67] years); 21 patients provided another specimen after lactulose administration for 55 [42–77] days. For each, a DNA library of V3 region of bacterial 16S ribosomal RNA was subjected to paired-end Illumina sequencing. Inter-specimen relationship was studied using principal co-ordinate analysis. Abundances of various bacterial taxa, and indices of alpha and beta diversity were compared, between patients and controls, and between specimens collected before and after lactulose.ResultsGut microbiota from cirrhosis patients and controls showed differential clustering, and microbiota from patients with cirrhosis had less marked alpha diversity. Abundances of dominant phyla (Bacteroidetes, Firmicutes and Proteobacteria) were similar. However, patients with cirrhosis had lower abundances of five phyla, namely Tenericutes, Cyanobacteria, Spirochaetes, Elusimicrobia and Lentisphaerae, and differences in abundances of several families and genera than in controls. Lactulose administration did not lead to any change in alpha and beta diversities, species richness and abundances of various bacterial taxa in gut microbiota.ConclusionsGut microbiota in cirrhosis differ from healthy persons and do not change following lactulose administration. The latter suggests that the effect of lactulose on hepatic encephalopathy may not be related to alteration in gut microbiota.Electronic supplementary materialThe online version of this article (10.1186/s12876-017-0683-9) contains supplementary material, which is available to authorized users.

Disease severity and proton pump inhibitor use impact strongest on faecal microbiome composition in liver cirrhosis

“…We were interested in the effect of lactulose on the cirrhotic microbiome, since available data are conflicting, showing no major alterations of the faecal microbiome between lactulose user and non-user, but withdrawal of lactulose leads to the loss of beneficial species. 16,50,51 In our cohort only 11% of the cirrhotic patients used lactulose. On univariate analysis we found that lactulose had a weak, but significant, effect on microbiome composition, which did not remain significant in multivariate analysis.…”

“…However, in our cohort, other drugs influenced microbiome composition to a lesser extent. We were interested in the effect of lactulose on the cirrhotic microbiome, since available data are conflicting, showing no major alterations of the faecal microbiome between lactulose user and non‐user, but withdrawal of lactulose leads to the loss of beneficial species . In our cohort only 11% of the cirrhotic patients used lactulose.…”

Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial

“…et al revealed that lactulose and probiotics could increase beneficial bacteria and reduce pathogenic bacteria in MHE. 15 Prior studies on lactulose and MHE are single-center experiences, 12,13 and a multicenter approach is lacking. In addition, the role of microbiota changes as mediators of lactulose responses need to be studied.…”

“…Lactulose, in studies primarily from India, has shown a beneficial impact on MHE reversal and on quality of life (QoL) . Further, Bajaj et al and Sarangi et al proved that NADs can beneficially affect microbiota composition. Thus, the therapeutic effect of lactulose for MHE was probably mediated by changing intestinal microbiota.…”

“…Prior studies on lactulose and MHE are single‐center experiences, and a multicenter approach is lacking. In addition, the role of microbiota changes as mediators of lactulose responses need to be studied.…”