Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Issue 10 (16th March 2014)

• Record Type: Journal Article
• Authors: Bajaj, J. S.; Heuman, D. M.; Hylemon, P. B.; Sanyal, A. J.; Puri, P.; Sterling, R. K.; Luketic, V.; Stravitz, R. T.; Siddiqui, M. S.; Fuchs, M.; Thacker, L. R.; Wade, J. B.; Daita, K.; Sistrun, S.; White, M. B.; Noble, N. A.; Thorpe, C.; Kakiyama, G.; Pandak, W. M.; Sikaroodi, M.; Gillevet, P. M.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 39:Issue 10(2014)
• Page Start: 1113
• Page End: 1125
• Publication Date: 2014-03-16
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.12695
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt12695-abs-0001"> <title>Summary</title> <sec id="apt12695-sec-0001" sec-type="section"> <title>Background</title> <p>Safety of individual probiotic strains approved under Investigational New Drug (IND) policies in cirrhosis with minimal hepatic encephalopathy (MHE) is not clear.</p> </sec> <sec id="apt12695-sec-0002" sec-type="section"> <title>Aim</title> <p>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.</p> </sec> <sec id="apt12695-sec-0003" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="apt12695-sec-0004" sec-type="section"> <title>Results</title> <p>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 <italic>Enterobacteriaceae</italic> and increased Clostridiales Incertae Sedis XIV and <italic>Lachnospiraceae</italic> relative abundance) with changes in metabolite/microbiome correlations pertaining to amino acid, vitamin and secondary BA metabolism. No change in cognition was found.</p> </sec> <sec id="apt12695-sec-0005" sec-type="section"> <title>Conclusions</title> <p>In this phase I study, Lactobacillus GG is safe and well‐tolerated in cirrhosis and is associated with a reduction in endotoxemia and dysbiosis.</p> </sec> </abstract>