Unveiling the survivability of probiotic CA15 strain with and without fluconazole co-administration and its effect on gut microbiota and metabolome through SHIME® model

The aim of the present study was to investigate the survival and functional impact of the probiotic Lacticaseibacillus rhamnosus CA15 strain on gut microbiota and metabolome, under simulated gastrointestinal conditions, through the SHIME® model. The experimental design included both fed and fasted conditions, and co-administration of fluconazole. A colonic incubation of up to 24 h was carried out, and CA15 availability was assessed using strain-specific RT-qPCR. In addition, the effects of the CA15 strain on metabolome and microbiota profiles were explored. Results showed that the fasted condition did not negatively affect the survival of the CA15 strain on the ileal stage. Moreover, fluconazole co-administration did not interfere with strain survivability. Meta-taxonomic 16S rRNA and metabolome profiles of the colonic fraction revealed significant variation in both microbial composition and metabolic compounds. Fluconazole determined a reduction of Firmicutes and an increase of Proteobacteria. In particular, a decrease of Dorea, Mitsuokella, Lactobacillus, Oscillospiraceae UCG-002, and Bifidobacterium genera, as well as Christensenellaceae_R-7_group and Eubacterium hallii. The co-administration of the CA15 strain, in the colonic fraction, counteracted the changes induces by the antimycotic treatment. Furthermore, CA15 administration significantly increased volatile organic compounds, short- and branched-chain fatty acids, particularly heptanoic, acetic, propanoic, and isobutyric acids. In conclusion, the CA15 stain demonstrated good survivability and a positive modulation of the gut microbiota and metabolome, supporting its potential as a functional probiotic. The use of the dynamic SHIME® model provided valuable insights into the delivery and performance of the probiotic CA15 strain on the GIT, under both fed and fasted conditions.