Treatment with mixed probiotics induced, enhanced and diversified modulation of the gut microbiome of healthy rats.

Previous studies demonstrated that multi-strain probitics could more strongly regulate intestinal cytokines and the mucosal barrier than the individual ingredient strains. Nevertheless, the potentially different gut microbiome modulation effects between multi-strain and single-strain probiotics treatments remain unexplored. Here, we administered three different Lactiplantibacillus plantarum strains or their mixture to healthy Wistar rats and compared the shift of gut microbiome among the treatment groups. A 4-week intervention with mixed probiotics induced more drastic and diversified gut microbiome modulation than single-strain probiotics administration (alpha diversity increased 8% and beta diversity increased 18.7%). The three single-strain probiotics treatments all converged the gut microbiota, decreasing between-individual beta diversity by 12.7% on average after the treatment, while multi-strain probiotics treatment diversified the gut microbiome and increased between-individual beta diversity by 37.2% on average. Covariation analysis of the gut microbes suggests that multi-strain probiotics could exert synergistic, modified and enhanced modulation effects on the gut microbiome based on strain-specific modulation effects of probiotics. The more heterogeneous responses to the multi-strain probiotics treatment suggest that future precision microbiome modulation should consider the potential interactions of the probiotic strains, and personalized response to probiotic formulas due to heterogenous gut microbial compositions.