BACKGROUND:Safety of individual probiotic strains approved under Investigational New Drug (IND) policies in cirrhosis with minimal hepatic encephalopathy (MHE) is not clear. AIM: The primary aim of this phase I study was to evaluate the safety, tolerability of probiotic Lactobacillus GG (LGG) compared to placebo, while secondary ones were to explore its mechanism of action using cognitive, microbiome, metabolome and endotoxin analysis in MHE patients. METHODS:Cirrhotic patients with MHE patients were randomised 1:1 into LGG or placebo BID after being prescribed a standard diet and multi-vitamin regimen and were followed up for 8 weeks. Serum, urine and stool samples were collected at baseline and study end. Safety was assessed at Weeks 4 and 8. Endotoxin and systemic inflammation, microbiome using multi-tagged pyrosequencing, serum/urine metabolome were analysed between groups using correlation networks. RESULTS:Thirty MHE patients (14 LGG and 16placebo) completed the study without any differences in serious adverse events. However, self-limited diarrhoea was more frequent in LGG patients. A standard diet was maintained and LGG batches were comparable throughout. Only in the LGG-randomised group, endotoxemia and TNF-α decreased, microbiome changed (reduced Enterobacteriaceae and increased Clostridiales Incertae Sedis XIV and Lachnospiraceae relative abundance) with changes in metabolite/microbiome correlations pertaining to amino acid, vitamin and secondary BA metabolism. No change in cognition was found. CONCLUSIONS: In this phase I study, Lactobacillus GG is safe and well-tolerated in cirrhosis and is associated with a reduction in endotoxemia and dysbiosis.
RCT Entities:
BACKGROUND: Safety of individual probiotic strains approved under Investigational New Drug (IND) policies in cirrhosis with minimal hepatic encephalopathy (MHE) is not clear. AIM: The primary aim of this phase I study was to evaluate the safety, tolerability of probiotic Lactobacillus GG (LGG) compared to placebo, while secondary ones were to explore its mechanism of action using cognitive, microbiome, metabolome and endotoxin analysis in MHE patients. METHODS:Cirrhoticpatients with MHE patients were randomised 1:1 into LGG or placebo BID after being prescribed a standard diet and multi-vitamin regimen and were followed up for 8 weeks. Serum, urine and stool samples were collected at baseline and study end. Safety was assessed at Weeks 4 and 8. Endotoxin and systemic inflammation, microbiome using multi-tagged pyrosequencing, serum/urine metabolome were analysed between groups using correlation networks. RESULTS: Thirty MHE patients (14 LGG and 16 placebo) completed the study without any differences in serious adverse events. However, self-limited diarrhoea was more frequent in LGG patients. A standard diet was maintained and LGG batches were comparable throughout. Only in the LGG-randomised group, endotoxemia and TNF-α decreased, microbiome changed (reduced Enterobacteriaceae and increased Clostridiales Incertae Sedis XIV and Lachnospiraceae relative abundance) with changes in metabolite/microbiome correlations pertaining to amino acid, vitamin and secondary BA metabolism. No change in cognition was found. CONCLUSIONS: In this phase I study, Lactobacillus GG is safe and well-tolerated in cirrhosis and is associated with a reduction in endotoxemia and dysbiosis.
Authors: Piero Amodio; Chantal Bemeur; Roger Butterworth; Juan Cordoba; Akinobu Kato; Sara Montagnese; Misael Uribe; Hendrik Vilstrup; Marsha Y Morgan Journal: Hepatology Date: 2013-05-31 Impact factor: 17.425
Authors: Zeneng Wang; Elizabeth Klipfell; Brian J Bennett; Robert Koeth; Bruce S Levison; Brandon Dugar; Ariel E Feldstein; Earl B Britt; Xiaoming Fu; Yoon-Mi Chung; Yuping Wu; Phil Schauer; Jonathan D Smith; Hooman Allayee; W H Wilson Tang; Joseph A DiDonato; Aldons J Lusis; Stanley L Hazen Journal: Nature Date: 2011-04-07 Impact factor: 49.962
Authors: Jasmohan S Bajaj; Douglas M Heuman; Arun J Sanyal; Phillip B Hylemon; Richard K Sterling; R Todd Stravitz; Michael Fuchs; Jason M Ridlon; Kalyani Daita; Pamela Monteith; Nicole A Noble; Melanie B White; Andmorgan Fisher; Masoumeh Sikaroodi; Huzefa Rangwala; Patrick M Gillevet Journal: PLoS One Date: 2013-04-02 Impact factor: 3.240
Authors: François P Douillard; Angela Ribbera; Ravi Kant; Taija E Pietilä; Hanna M Järvinen; Marcel Messing; Cinzia L Randazzo; Lars Paulin; Pia Laine; Jarmo Ritari; Cinzia Caggia; Tanja Lähteinen; Stan J J Brouns; Reetta Satokari; Ingemar von Ossowski; Justus Reunanen; Airi Palva; Willem M de Vos Journal: PLoS Genet Date: 2013-08-15 Impact factor: 5.917