| Summary: | Interest in preventive or therapeutic strategies targeting gut microbiota is increasing. Such strategies may involve the direct replenishment of the gut microbiota with single strains or strain mixtures, or the manipulation of strain abundance through dietary intervention, including lactic acid bacteria. A few candidate species associated with health benefits have been identified, including <i>Faecalibacterium prausnitzii</i>. Given its growth requirements, modulation of this bacterium has not been extensively studied. In this investigation, we explored the capacity of cell-free supernatants of different <i>Lactobacillus</i>, <i>Streptococcus</i>, <i>Lactococcus,</i> and <i>Bifidobacterium</i> strains to stimulate the growth of <i>F. prausnitzii</i> A2-165. Modulation by four strains with the greatest capacity to stimulate growth or delay lysis, <i>Lactococcus lactis</i> subsp. lactis CNCM I-1631, <i>Lactococcus lactis</i> subsp. <i>cremoris</i> CNCM I-3558, <i>Lactobacillus paracasei</i> CNCM I-3689, and <i>Streptococcus thermophilus</i> CNCM I-3862, was further characterized by transcriptomics. The response of <i>F. prausnitzii</i> to cell-free supernatants from these four strains revealed several shared characteristics, in particular, upregulation of carbohydrate metabolism and cell wall-related genes and downregulation of replication and mobilome genes. Overall, this study suggests differential responses of <i>F. prausnitzii</i> to metabolites produced by different strains, providing protection against cell death, with an increase in peptidoglycan levels for cell wall formation, and reduced cell mobilome activity.
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