Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis

Abstract

SummaryBackgroundProbiotics may correct intestinal dysbiosis and proinflammatory conditions in patients with liver cirrhosis.AimTo test the effects of a multispecies probiotic on innate immune function, bacterial translocation and gut permeability.MethodsIn a randomised, double blind, placebo‐controlled study, stable cirrhotic out‐patients either received a daily dose of a probiotic powder containing eight different bacterial strains (Ecologic Barrier, Winclove, Amsterdam, The Netherlands) (n = 44) or a placebo (n = 36) for 6 months and were followed up for another 6 months.ResultsWe found a significant but subclinical increase in neutrophil resting burst (2.6–3.2%, P = 0.0134) and neopterin levels (7.7–8.4 nmol/L, P = 0.001) with probiotics but not with placebo. Probiotic supplementation did not have a significant influence on neutrophil phagocytosis, endotoxin load, gut permeability or inflammatory markers. Ten severe infections occurred in total; one during intervention in the placebo group, and five and four after the intervention has ended in the probiotic and placebo group, respectively. Liver function showed some improvement with probiotics but not with placebo.ConclusionsProbiotic supplementation significantly increased serum neopterin levels and the production of reactive oxygen species by neutrophils. These findings might explain the beneficial effects of probiotics on immune function. Furthermore, probiotic supplementation may be a well‐tolerated method to maintain or even improve liver function in stable cirrhosis. However, its influence on gut barrier function and bacterial translocation in cirrhotic patients is minimal.

Effect of a Multistrain Probiotic on Cognitive Function and Risk of Falls in Patients With Cirrhosis: A Randomized Trial

“…(38,39) This finding has also been reported in models of experimental cirrhosis, in which several probiotics improved the intestinal barrier, decreased bacterial translocation, and ameliorated the proinflammatory state. (40,41) However, in the study by Horvath et al (37) in patients with cirrhosis treated with a different probiotic mixture, the authors did not observe any significant effect on gut permeability, as assessed by a panel of markers including lactulose/ mannitol ratio and fecal zonulin, or inflammatory biomarkers. Liu et al (42) evaluated patients undergoing colorectal surgery treated with a three-strain probiotic and reported a decrease in serum zonulin, a parameter that was unchanged in our study.…”

“…This effect was probably a consequence of an improvement in pathological bacterial translocation, as suggested by the decrease in the neutrophil toll-like receptor 4 expression after stimulation with endotoxin in patients treated with the probiotic. (36) In a more recent study, Horvath et al (37) reported that treatment with a different multispecies probiotic in outpatients with cirrhosis produced an immune modulation consisting of an increase in neutrophil resting oxidative burst and serum neopterin, a marker of macrophage activation.…”

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

“…We included faecal 16S microbiome sequencing data from cirrhotic patients recruited at the outpatient clinic of the Department of Gastroenterology and Hepatology, University Hospital of Graz, Austria who were screened for an intervention study between July 2012 and September 2013 in this post‐hoc analysis. All patients gave written informed consent.…”

“…Enzyme linked immunosorbent assay were used to measure calprotectin, zonulin and serum DAO (Immundiagnostic AG, Bensheim, Germany), as well as LBP and sCD14 (Hycult biotechnology, Uden, the Netherlands). sCD163 and sMR in plasma samples were measured by an in‐house sandwich ELISA using a BEP‐2000 ELISA‐analyser (Dade Behring) as previously described …”

“…Compared to healthy individuals, a decrease in faecal microbial diversity and an imbalance between commensal and pathogenic taxa is seen in patients with cirrhosis. Furthermore, cirrhosis‐associated dysbiosis goes hand in hand with increased gut permeability, intestinal bacterial translocation, intestinal and systemic inflammation leading to complications of cirrhosis and an increased mortality . Dysbiosis in general and especially in cirrhosis may be caused by host and environmental factors, which shape the microbiome.…”