Development of a novel potentially psychobiotic, plant-based fermented product: evaluation of the impact on the gut microbiome in m-SHIME® model

Modulating the gut microbiome through diet could positively influence mental health, offering new perspectives for dietary approaches in the treatment and prevention of mental disorders. Many lactic acid bacteria (LAB) found in fermented food are major microbial producers of neuroactive compounds. Three LAB strains, Limosilactobacillus (Lmb.) fermentum TO24, Levilactobacillus (Lvb.) brevis TO10, and Lentilactobacillus (Llb.) diolivorans B92, previously isolated from fermented foods, were used to ferment a plant-based matrix to develop a plant-based yogurt-like (pYL) product. We demonstrated that the strains were able to produce neuroactive compounds during fermentation and that remained stable during refrigerated storage of the pYL. The pYL was administered daily for 11 days to a m-SHIME® model simulating the gut microbiome of a depressed patient. The abundance of the pYL strains Lvb. brevis and Lmb. fermentum increased during treatment in both the lumen and mucosa samples, with Lvb. brevis persisting after the washout phase. The pYL treatment significantly inhibited potentially pro-inflammatory taxa (Acidaminococcus intestini and Megasphaera massiliensis) in both compartments. Notably, the neuroactive potential was not limited to the introduced strains. A significant functional redundancy emerged, as commensal Metagenome-Assembled Genomes (MAGs) were associated with key functional hubs involved in GABA biosynthesis. These encouraging findings suggest that the pYL treatment can modulate and partially restore the dysbiotic gut microbiome in depressed patients. Gut microbiome modulation through fermented foods consumption may represent a viable therapeutic strategy for mitigating mental diseases.