A multi-strain probiotic modulates gut microbiome composition, intestinal barrier integrity and inflammation in a multi-compartmental in vitro gut model of decompensated advanced chronic liver disease

Decompensated advanced chronic liver disease (dACLD), which is defined by the onset and worsening of clinical complications that require hospitalisation and can lead to organ dysfunction, is pathobiologically characterised by an altered gut microbiome composition and function, intestinal barrier failure, immune dysfunction and systemic inflammation. The gut microbiome represents a promising therapeutic target in dACLD to prevent the onset of such life-threatening clinical complications. We investigated the effect of a live, multi-strain, aqueous probiotic suspension (Symprove™) on faecal material from three people with alcohol-related dACLD utilising an advanced in vitro gut model. We evaluated the impact of Symprove™ on mucosal and luminal bacterial microbiome diversity after 48 h by 16S rRNA gene sequencing. The effect on epithelial tight-junction (TJ) integrity was estimated using transepithelial electrical resistance measurement. We quantified metabolites, anti-inflammatory markers, chemokines and epithelial wound healing pre- and post-treatment in cell culture models. The relative proportions of the main bacterial phyla differed from those of healthy subjects studied previously: levels of Firmicutes decreased and Bacteroidetes increased. Dosing with Symprove™ resulted in faecal microbiome modulation over a 48 h period. Surrogate indicators of gut barrier integrity and mucosal immunity improved with Symprove™ exposure. Estimated TJ integrity and epithelial wound healing improved and short chain fatty acids and anti-inflammatory cytokine production (IL-6 and IL-10) increased, whilst pro-inflammatory chemokines (MCP-1 and IL-8) decreased. These data support Symprove^TM as a potential gut microbiome-targeting therapeutic for people with dACLD and warrants further investigation.