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.

The gut microbiome composition of people with alcohol-related dACLD differed from healthy subjects, with decreased Firmicutes and increased Bacteroidetes.

• Faecal material was obtained from three people with alcohol-related dACLD.
• The relative proportions of the main bacterial phyla differed from those of healthy subjects studied previously.
• Levels of Firmicutes decreased and Bacteroidetes increased compared to healthy subjects.
• 16S rRNA gene sequencing was used to evaluate mucosal and luminal bacterial microbiome diversity.

Dosing with Symprove™ resulted in faecal microbiome modulation over a 48-hour period.

• A live, multi-strain, aqueous probiotic suspension (Symprove™) was applied to faecal material from three people with alcohol-related dACLD.
• Microbiome modulation was evaluated after 48 hours using 16S rRNA gene sequencing.
• Both mucosal and luminal bacterial microbiome diversity were assessed.
• An advanced multi-compartmental in vitro gut model was used for the experiment.

Symprove™ exposure improved surrogate indicators of gut barrier integrity, including estimated tight-junction integrity and epithelial wound healing.

• Tight-junction integrity was estimated using transepithelial electrical resistance (TEER) measurement.
• Epithelial wound healing was quantified pre- and post-treatment in cell culture models.
• Both TEER and epithelial wound healing improved with Symprove™ exposure.
• These improvements were observed in the context of a multi-compartmental in vitro gut model.

Symprove™ treatment increased short chain fatty acid production and anti-inflammatory cytokine levels (IL-6 and IL-10).

• Short chain fatty acids (SCFAs) were quantified as metabolites pre- and post-treatment.
• Anti-inflammatory markers IL-6 and IL-10 were measured in cell culture models.
• Both SCFA production and anti-inflammatory cytokine levels increased following Symprove™ exposure.
• Measurements were taken pre- and post-treatment to assess changes.

Symprove™ treatment decreased pro-inflammatory chemokines MCP-1 and IL-8.

• Pro-inflammatory chemokines MCP-1 and IL-8 were quantified pre- and post-treatment in cell culture models.
• Levels of both MCP-1 and IL-8 decreased following Symprove™ exposure.
• This reduction in pro-inflammatory chemokines was observed alongside increases in anti-inflammatory markers.
• Chemokine quantification was performed as part of a broader assessment of mucosal immunity indicators.

Decompensated advanced chronic liver disease is pathobiologically characterised by altered gut microbiome composition, intestinal barrier failure, immune dysfunction, and systemic inflammation.

• dACLD is defined by the onset and worsening of clinical complications that require hospitalisation and can lead to organ dysfunction.
• The gut microbiome represents a promising therapeutic target in dACLD to prevent life-threatening clinical complications.
• This pathobiological characterisation provided the rationale for investigating a probiotic intervention in dACLD.
• The study focused specifically on alcohol-related dACLD.

The authors concluded that Symprove™ is a potential gut microbiome-targeting therapeutic for people with dACLD warranting further investigation.

• Data from the in vitro multi-compartmental gut model supported Symprove™ as a potential therapeutic.
• Improvements were observed across microbiome modulation, barrier integrity, metabolite production, and inflammatory markers.
• The study used faecal material from only three people with alcohol-related dACLD.
• The authors stated the findings 'warrant further investigation' in their conclusion.