Unveiling the influence of a probiotic combination of Heyndrickxia coagulans and Lacticaseibacillus casei on healthy human gut microbiota using the TripleSHIME® system

Abstract

Probiotics are host-friendly microorganisms that can have important health benefits in the human gut microbiota as dietary supplements. Maintaining a healthy gut microbial balance relies on the intricate interplay among the intestinal microbiota, metabolic activities, and the host's immune response. This study aims to explore if a mixture of Heyndrickxia coagulans [ATB-BCS-042] and Lacticaseibacillus casei [THT-030-401] promotes in vitro this balance in representative gut microbiota from healthy individuals using the Triple-SHIME® (Simulation of the Human Intestinal Microbial Ecosystem). Metataxonomic analysis of the intestinal microbes revealed that the probiotic mix was not causing important disruptions in the biodiversity or microbial composition of the three simulated microbiota. However, some targeted populations analyzed by qPCR were found to be disrupted at the end of the probiotic treatment or after one week of washout. Populations such as Cluster IV, Cluster XVIa, and Roseburia spp., were increased indicating a potential gut health-promoting butyrogenic effect of the probiotic supplementation. In two of the systems, bifidogenic effects were observed, while in the third, the treatment caused a decrease in bifidobacteria. For the health-detrimental biomarker Escherichia-Shigella, a mild decrease in all systems was observed in the proximal colon sections, but these genera were highly increased in the distal colon sections. By the end of the washout, Bacteroides-Prevotella was found consistently boosted, which could have inflammatory consequences in the intestinal context. Although the probiotics had minimal influence on most quantified metabolites, ammonia consistently decreased after one week of daily probiotic supplementation. In reporter gene assays, aryl hydrocarbon receptor (AhR) activation was favored by the metabolic output obtained from post-treatment periods. Exposure of a human intestinal cell model to fermentation supernatant obtained after probiotic supplementation induced a trend to decrease the mRNA expression of immunomodulatory cytokines (IL-6, IL-8). Overall, with some exceptions, a positive impact of H. coagulans and L. casei probiotic mix was observed in the three parallel experiments, despite inter-individual differences. This study might serve as an in vitro pipeline for the impact assessment of probiotic combinations on the human gut microbiota.