Untargeted metabolomics reveals distinct metabolic profiles and putative bioactive metabolites in cell-free supernatants of food-grade microorganisms
- 1Proteomics and Metabolomics Facility (ProMeFa), Center for Omics Sciences (COSR), IRCCS San Raffaele Scientific Institute , ,
- 2NTP Biotech S.r.l. , ,
- 3PNK Farmaceutici S.p.A. , ,
Abstract
Over the past decade, the understanding of the role of microorganisms in health and disease has expanded considerably, with many of the beneficial effects traditionally attributed to probiotics now also being associated with their metabolites, collectively referred to as postbiotics. In this context, postbiotics are increasingly being explored as complementary components of broader microbiome-centered strategies. Fermentation supernatants are commonly regarded as industrial by-products; however, they contain a diverse repertoire of microbially derived metabolites with potential biological relevance. The valorization of these fermentation streams therefore represents a promising strategy for identifying novel compounds capable of modulating host physiology. Five food-grade microorganisms- Lactobacillus amylovorus SGL 14, Bifidobacterium breve SGB 01, Lentilactobacillus kefiri SGL 13, Lactiplantibacillus plantarum SGL 07, and Ligilactobacillus salivarius SGL 03-were cultured under standardized conditions, and their cell-free supernatants were characterized using untargeted metabolomics to identify differential metabolic profiles. Each strain displayed a distinctive metabolomic signature enriched in metabolites previously associated in the literature with potential biological activities. Collectively, the identified compounds have been linked to antimicrobial, immunomodulatory, neuroactive, antioxidant, epithelial-supportive, and metabolic functions. However, the present study did not include direct functional validation of these activities, and the proposed biological relevance of the detected metabolites should therefore be considered putative and inferred from previous literature evidence. Overall, untargeted metabolomics/lipidomics revealed that fermentation media derived from food-grade microorganisms represent a valuable and underexplored source of multifunctional metabolites with potential postbiotic applications. These findings support the concept of valorizing microbial fermentation by-products as sustainable reservoirs of biologically relevant molecules within a circular bioeconomy framework. In industrial settings, fermentation broths traditionally considered waste streams may be recovered and repurposed, potentially reducing disposal costs and environmental impact. Furthermore, optimization of fermentation processes prior to large-scale metabolite production will be essential to maximize yield, improve process efficiency, and support their future development for nutraceutical and health-related applications.
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BibTeX
@article{drago2026untargeted,
title = {{Untargeted metabolomics reveals distinct metabolic profiles and putative bioactive metabolites in cell-free supernatants of food-grade microorganisms}},
author = {Denise Drago and Luca Marini and Eleonora Bafile and Federica Federici and Radmila Pavlovic and Marynka Ulaszewska and Gianfranco Frigerio and Laura Manna and Annapaola Andolfo},
journal = {Frontiers in microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1854827},
url = {https://europepmc.org/article/PMC/PMC13673657},
note = {CC BY},
}
RIS
TY - JOUR
TI - Untargeted metabolomics reveals distinct metabolic profiles and putative bioactive metabolites in cell-free supernatants of food-grade microorganisms
AU - Denise Drago
AU - Luca Marini
AU - Eleonora Bafile
AU - Federica Federici
AU - Radmila Pavlovic
AU - Marynka Ulaszewska
AU - Gianfranco Frigerio
AU - Laura Manna
AU - Annapaola Andolfo
PY - 2026
DA - 2026/10/02
JO - Frontiers in microbiology
DO - 10.3389/fmicb.2026.1854827
UR - https://europepmc.org/article/PMC/PMC13673657
AB - Over the past decade, the understanding of the role of microorganisms in health and disease has expanded considerably, with many of the beneficial effects traditionally attributed to probiotics now also being associated with their metabolites, collectively referred to as postbiotics. In this context, postbiotics are increasingly being explored as complementary components of broader microbiome-centered strategies. Fermentation supernatants are commonly regarded as industrial by-products; however, they contain a diverse repertoire of microbially derived metabolites with potential biological relevance. The valorization of these fermentation streams therefore represents a promising strategy for identifying novel compounds capable of modulating host physiology. Five food-grade microorganisms- Lactobacillus amylovorus SGL 14, Bifidobacterium breve SGB 01, Lentilactobacillus kefiri SGL 13, Lactiplantibacillus plantarum SGL 07, and Ligilactobacillus salivarius SGL 03-were cultured under standardized conditions, and their cell-free supernatants were characterized using untargeted metabolomics to identify differential metabolic profiles. Each strain displayed a distinctive metabolomic signature enriched in metabolites previously associated in the literature with potential biological activities. Collectively, the identified compounds have been linked to antimicrobial, immunomodulatory, neuroactive, antioxidant, epithelial-supportive, and metabolic functions. However, the present study did not include direct functional validation of these activities, and the proposed biological relevance of the detected metabolites should therefore be considered putative and inferred from previous literature evidence. Overall, untargeted metabolomics/lipidomics revealed that fermentation media derived from food-grade microorganisms represent a valuable and underexplored source of multifunctional metabolites with potential postbiotic applications. These findings support the concept of valorizing microbial fermentation by-products as sustainable reservoirs of biologically relevant molecules within a circular bioeconomy framework. In industrial settings, fermentation broths traditionally considered waste streams may be recovered and repurposed, potentially reducing disposal costs and environmental impact. Furthermore, optimization of fermentation processes prior to large-scale metabolite production will be essential to maximize yield, improve process efficiency, and support their future development for nutraceutical and health-related applications.
SN - 1664-302X
ER -