Characterisation of the immunomodulatory, antiviral and gut microbiome-modulatory potential of a novel dairy fermentate of Lactobacillus delbrueckii subsp. bulgaricus SC40
Da[AM1.1]iry fermentates derived from lactic acid bacteria represent a promising class of postbiotic ingredients with potential immunomodulatory and microbiota-modulatory activity. In this study, we report the multi-modal characterisation of a heat-inactivated fermentate produced by Lactobacillus delbrueckii subsp. bulgaricus SC40, encompassing strain and product safety, metabolite profiling, immunomodulation and impact on the gut microbiome. Whole-genome screening of SC40 confirmed the absence of acquired antimicrobial resistance genes, virulence determinants, and mobile genetic elements, with minimum inhibitory concentrations within EFSA Qualified Presumption of Safety breakpoints. ¹H-NMR profiling identified 33 significantly modified metabolites relative to uninoculated medium, with SC40 enriching desaminotyrosine, a toll-like receptor 7 agonist, alongside lactate, acetate, and a spectrum of amino acids. In murine macrophage and dendritic cell models, SC40 potentiated both pro-inflammatory (IL-1ß, IL-6, TNF-a) and counter-regulatory (IL-10) cytokine secretion, augmented nitric oxide production and phagocytic activity, and suppressed MCP-1 across TLR7 and TLR4 stimulation contexts. Simultaneous induction of nitric oxide synthase and arginase activities by SC40 indicated engagement of opposing macrophage polarisation programmes. Metagenomic evaluation of faecal fermentations in an ex vivo model of the human distal colon further revealed a fermentate-specific bifidogenic effect and depletion of Clostridium perfringens, with no between-group difference in short-chain fatty acid output. Functional profiling identified 42 metabolic pathways enriched by SC40 in the gut microbiome, predominantly driven by Bififdobacterium longum, including aromatic amino acid biosynthesis routes supported by 292 significant taxon–pathway correlations. Collectively, these findings characterise SC40 as a context-dependent immune primer and microbiota modulator with potential as a functional food ingredient.
Da[AM1.1]iry fermentates derived from lactic acid bacteria represent a promising class of postbiotic ingredients with potential immunomodulatory and microbiota-modulatory activity. In this study, we report the multi-modal characterisation of a heat-inactivated fermentate produced by Lactobacillus delbrueckii subsp. bulgaricus SC40, encompassing strain and product safety, metabolite profiling, immunomodulation and impact on the gut microbiome. Whole-genome screening of SC40 confirmed the absence of acquired antimicrobial resistance genes, virulence determinants, and mobile genetic elements, with minimum inhibitory concentrations within EFSA Qualified Presumption of Safety breakpoints. ¹H-NMR profiling identified 33 significantly modified metabolites relative to uninoculated medium, with SC40 enriching desaminotyrosine, a toll-like receptor 7 agonist, alongside lactate, acetate, and a spectrum of amino acids. In murine macrophage and dendritic cell models, SC40 potentiated both pro-inflammatory (IL-1ß, IL-6, TNF-a) and counter-regulatory (IL-10) cytokine secretion, augmented nitric oxide production and phagocytic activity, and suppressed MCP-1 across TLR7 and TLR4 stimulation contexts. Simultaneous induction of nitric oxide synthase and arginase activities by SC40 indicated engagement of opposing macrophage polarisation programmes. Metagenomic evaluation of faecal fermentations in an ex vivo model of the human distal colon further revealed a fermentate-specific bifidogenic effect and depletion of Clostridium perfringens, with no between-group difference in short-chain fatty acid output. Functional profiling identified 42 metabolic pathways enriched by SC40 in the gut microbiome, predominantly driven by Bififdobacterium longum, including aromatic amino acid biosynthesis routes supported by 292 significant taxon–pathway correlations. Collectively, these findings characterise SC40 as a context-dependent immune primer and microbiota modulator with potential as a functional food ingredient.