The Neuroactive Potential of Cheeses

By Raffaele Magliulo

Keywords: cheese, microbiome, psychobiotics

What if the benefits of traditional cheeses expanded far beyond aroma and nutrition? Can long-ripened cheeses like Parmigiano Reggiano, Trentingrana, and Grana Padano influence not only flavor and safety, but also the gut-brain axis? These questions inspired our recent study investigating how cheesemaking processes shape microbial communities and their biological roles. Cheeses are complex food systems that host dynamic microbial communities capable of producing bioactive molecules that may interact with human physiology (1). Within this context, the concept of psychobiotics – microbial strains with potential mental health benefits (2) – has attracted growing scientific interest. Could traditional Protected Designation of Origin (PDO) cheeses serve as reservoirs of functional, potentially mental health-relevant microbes? Our recent multiomics study set out to answer this question, among others.

Cheeses from a microbial ecology perspective

The cheese microbiome develops throughout craftsmanship, fermentation, and ripening, playing a central role in shaping texture, aroma, and nutritional quality (3). In long-ripened cheeses, microbial metabolism becomes particularly important. Once lactose is depleted, non-starter lactic acid bacteria begin degrading proteins and lipids, releasing peptides, amino acids, and volatile compounds that define the characteristic sensory profile of aged cheeses (1-3). Our work aimed to demonstrate that these microbial activities do more than drive flavor development – they also generate molecules with potential relevance for food safety, shelf life, and human health.

Exploring PDO cheeses using multiomics

To address these questions, we conducted a multiomics analysis of 120 samples of Parmigiano Reggiano, Trentingrana, and Grana Padano, combining metagenomics, volatilomics, and metaproteomics to characterize microbial composition and metabolic potential.

Raffaele presenting this research at the FoodMicro2024 Conference

Although these cheeses share similar production regulations, we observed clear microbiome differences. Grana Padano and Trentingrana formed two distinct clusters despite belonging to the same PDO designation, with Trentingrana proving more closely related to Parmigiano Reggiano. These patterns reflected differences in milk processing, animal feeding, lysozyme use, and ripening conditions, showing that cheesemaking technology leaves measurable microbial and functional signatures in the final product.

Psychobiotic potential and neuroactive molecules

One of the most innovative aspects of our study was the exploration of neuroactive metabolic pathways. We detected genes involved in the synthesis or transport of compounds including γ-aminobutyric acid, propionate, conjugated linoleic acid, tryptophan, and taurine. Many of these molecules are known to interact with gut-brain signaling and neural function. Importantly, several of these genes were also detected at the protein level, indicating active expression during ripening and strengthening the biological relevance of our observations. Non-starter lactic acid bacteria, particularly Lentilactobacillus and Lactobacillus species, emerged as major contributors to these pathways, suggesting that long-ripened cheeses may represent underexplored sources of potential psychobiotic strains.

Implications for health, authenticity, and the food industry

Our findings have several important implications. First, they demonstrate that PDO cheeses carry measurable microbial and functional fingerprints shaped by processing and geography. These biomarkers could strengthen authentication tools and support the protection of traditional products. Second, the identification of neuroactive molecules highlights new opportunities for exploring fermented foods in relation to gut-brain communication. Although clinical validation is still required, our results provide a strong biological foundation for future studies. Third, understanding microbial metabolism can support innovation in artisanal and industrial cheesemaking. By preserving beneficial microbial consortia, producers may enhance flavor, safety, and functional value simultaneously.

Take-home message

Can traditional cheeses contribute to health, safety, and sustainability through their microbiome? Our research shows that long-ripened PDO cheeses host specialized microbial communities shaped by processing technology. These communities are linked to flavor development, natural bioprotection, and the production of potentially neuroactive compounds. While direct clinical benefits remain to be demonstrated, our findings highlight the multifunctional nature of fermented foods. They are not only cultural and gastronomic products but also biologically active systems with relevance for nutrition, mental health research, and food innovation. As interest in fermented foods and gut microbiome health continues to grow, understanding how traditional cheesemaking generates bioactive compounds may unlock new opportunities for producers, researchers, and industry stakeholders.

References

1. Afshari, R., Pillidge, C. J., Dias, D. A., Osborn, A. M. & Gill, H. Cheesomics: the future pathway to understanding cheese flavour and quality. Crit. Rev. Food Sci. Nutr. 60, 33–47 (2020).

2. Dinan, T. G., Stanton, C. & Cryan, J. F. Psychobiotics: a novel class of psychotropic. Biol. Psychiatry 74, 720–726 (2013).

3. De Filippis, F., Genovese, A., Ferranti, P., Gilbert, J. A. & Ercolini, D. Metatranscriptomics reveals temperature-driven functional changes in microbiome impacting cheese maturation rate. Sci. Rep. 6, 21871 (2016).

ISAPP_SFAApril 14, 2026