Synbiotics of Bifidobacterium breve MCC1274 and lactulose enhances production of tryptophan metabolites in fermented human fecal communities.

Probiotics and prebiotics have beneficial effects on host physiology via metabolites from the gut microbiota in addition to their own. Here, we used a pH-controlled single-batch fermenter as a human gut microbiota model. We conducted fecal fermentation with Bifidobacterium breve MCC1274 (probiotic), lactulose (prebiotic), or a combination of both (synbiotic) to evaluate their influence on the gut environment. Fecal inoculum without the probiotic and prebiotic was used as the control. Principal coordinate analysis (PCoA), based on the composition of gut microbiota, showed a significant difference among the groups. The relative abundance of Bifidobacterium was significantly higher in the synbiotic group, compared to that in the other three treatment groups. The relative abundance of Blautia was the highest in the control group among the four groups. CE-TOFMS and LC-TOFMS showed that the number of metabolites detected in the synbiotic group was the highest (352 in total); 29 of the 310 hydrophilic metabolites and 17 of the 107 lipophilic metabolites were significantly different among the four groups in the Kruskal-Wallis test. A clustering based on 46 metabolites indicated that tryptophan-metabolites such as indole-3-lactic acid (ILA), indole-3-ethanol, and indole-3-carboxaldehyde, were included in a sub cluster composed of metabolites enriched in the synbiotic group. Spermidine, a major polyamine, was enriched in the two groups supplemented with the probiotic whereas spermine was enriched only in the synbiotic group. Not all metabolites enriched in the probiotic and/or synbiotic groups were found in the monocultures of the probiotic strain with or without the prebiotics. This implies that some of the metabolites were produced through the interaction of the fecal microbiota with the inoculated probiotic strain. Co-abundance networking analysis indicated the differences in the correlations between the relative abundance of the fecal microbiota genus and the tryptophan metabolites in each group. There was a strong correlation between ldh4 gene abundance and ILA concentration in the fecal fermentation. The copy number of ldh4 gene was significantly higher in the groups with the probiotic than that in the control group. In conclusion, synbiotics could enhance the production of signaling molecules in the gut environment. Our results provide an insight into more effective administration of probiotics at the molecular level.