Weizmannia coagulans BC99 alleviates alcohol-induced oxidative stress and gut barrier dysfunction via modulation of butyrate metabolism: A randomized, double-blind, placebo-controlled trial.

Weizmannia coagulans BC99 supplementation significantly increased the activities of alcohol dehydrogenase (ADH1) and aldehyde dehydrogenase (ALDH2), indicating enhanced ethanol metabolism.

• Study design: randomized, double-blind, placebo-controlled clinical trial
• Sixty participants were randomly assigned to receive either BC99 or placebo for 60 days
• Participants were adults with chronic alcohol consumption
• ADH1 and ALDH2 activity increases were significant compared with placebo

BC99 supplementation improved serum lipid profiles, reflected by a significant reduction in triglycerides (TG).

• The reduction in TG was statistically significant compared to placebo
• Duration of intervention was 60 days
• Participants were chronic alcohol consumers (n=60 total)
• TG reduction was one of several metabolic improvements observed

BC99 supplementation markedly alleviated oxidative stress as shown by increased serum SOD and GSH and decreased MDA and CYP2E1 levels.

• Superoxide dismutase (SOD) and glutathione (GSH) levels increased significantly following BC99 intervention
• Malondialdehyde (MDA) levels decreased significantly, indicating reduced lipid peroxidation
• CYP2E1 (P450 2E1) levels were decreased, suggesting reduced oxidative alcohol metabolism via this pathway
• Changes were significant compared with placebo group

Serum lipopolysaccharide (LPS) concentrations were significantly reduced following BC99 supplementation, suggesting improved intestinal barrier integrity.

• LPS reduction was significant compared to placebo
• LPS is used as a biomarker of intestinal barrier dysfunction and bacterial translocation
• Improved intestinal barrier integrity is a key proposed mechanism of BC99's protective effects
• LPS levels were negatively correlated with metabolites involved in butyrate metabolism

Fecal short-chain fatty acids (SCFAs), particularly butyrate, increased substantially following BC99 intervention.

• Butyrate was identified as the primary SCFA increased by BC99 supplementation
• Fecal SCFA levels were measured as an indicator of gut microbial metabolic activity
• The increase in butyrate was associated with reduced LPS and oxidative stress biomarkers
• KEGG enrichment analysis revealed significant modulation of butyrate metabolism pathway

Untargeted serum metabolomics identified 590 differentially regulated metabolites after BC99 supplementation.

• Metabolomics analysis was untargeted and performed on serum samples
• 590 differentially regulated metabolites were identified between BC99 and placebo groups
• KEGG enrichment analysis revealed significant modulation of butyrate metabolism, purine metabolism, and histidine metabolism pathways
• Metabolites involved in butyrate metabolism were negatively correlated with LPS and oxidative stress biomarkers

Metabolites involved in butyrate metabolism were negatively correlated with LPS and oxidative stress biomarkers, indicating a potential mechanistic link between enhanced SCFA metabolism and improved systemic oxidative and inflammatory status.

• The correlation analysis linked butyrate metabolism metabolites inversely to both LPS concentrations and oxidative stress markers
• This association suggests butyrate-related pathways may mediate BC99's protective effects on gut barrier and oxidative status
• The finding supports butyrate metabolism modulation as a candidate mechanism for BC99's therapeutic effects
• This mechanistic link was identified through integration of metabolomics and clinical biomarker data