Safety of individual probiotic strains approved under Investigational New Drug (IND) policies in cirrhosis with minimal hepatic encephalopathy is not clear.
Dr Bajaj and colleagues from Virginia, USA performed a phase I study to evaluate the safety, tolerability of probiotic Lactobacillus GG (LGG) compared to placebo.
The team's secondary aims were to explore its mechanism of action using cognitive, microbiome, metabolome and endotoxin analysis in minimal hepatic encephalopathy patients.
Cirrhotic patients with minimal hepatic encephalopathy patients were randomized 1:1 into LGG or placebo BID after being prescribed a standard diet and multi-vitamin regimen and were followed up for 8 weeks.
The team collected serum, urine and stool samples at baseline and study end.
Safety was assessed at Weeks 4 and 8.
|TNF-α decreased on in the LGG-randomized group|
|Alimentary Pharmacology & Therapeutics|
Endotoxin and systemic inflammation, microbiome using multi-tagged pyrosequencing, serum/urine metabolome were analyzed between groups using correlation networks.
The team observed that 30 minimal hepatic encephalopathy patients completed the study without any differences in serious adverse events.
The team noted that self-limited diarrhea was more frequent in LGG patients.
A standard diet was maintained and LGG batches were comparable throughout.
The researchers found that only in the LGG-randomized group, endotoxemia and TNF-α decreased, microbiome changed with changes in metabolite/microbiome correlations pertaining to amino acid, vitamin and secondary BA metabolism.
The team found no change in cognition.
Dr Bajaj's team comments, "In this phase I study, Lactobacillus GG is safe and well-tolerated in cirrhosis, and is associated with a reduction in endotoxemia and dysbiosis."