Postbiotics are emerging as a promising frontier in healthcare, acting as key mediators between the gut microbiota and the host. Within the broader “biotic continuum” that includes prebiotics, probiotics, and postbiotics, microbial metabolites represent the final functional output of microbiota activity. These molecules can act locally on immune, endocrine, and epithelial cells, contributing to mucosal homeostasis, and may also enter the circulation, influencing the physiology of distant organs.

In this interview, Giuseppe Penna, from Humanitas University (Italy) discusses the role of postbiotics in relation to intestinal barrier integrity, dysbiosis, and systemic health. When microbial balance is disrupted, the production of beneficial metabolites may be altered, weakening several layers of the gut barrier, including the mucus layer, the intestinal epithelial barrier, and the gut vascular barrier. This process may contribute to increased intestinal permeability, often referred to as “leaky gut,” with potential consequences for multiple organs and body systems.

The interview also presents the development of a novel postbiotic obtained from a single bacterial strain through an innovative fermentation process. Unlike traditional fermented products, this preparation does not contain live or dead microbial cells, but only metabolites released during fermentation. Preclinical studies have shown its ability to modulate immune responses, interfere with biofilm production, and improve intestinal barrier function.

Based on these findings, clinical trials have been designed in patients with irritable bowel syndrome, a condition increasingly associated with altered intestinal permeability. In parallel, the postbiotic has shown potential relevance in oncology by increasing the expression of HLA class I molecules on tumor cells, which are essential for immune recognition by CD8 T cells. In preclinical models of triple-negative breast cancer, oral administration of the postbiotic enhanced the efficacy of immune checkpoint blockade.

These results have led to the design of randomized, double-blind, placebo-controlled clinical trials in triple-negative breast cancer, with further studies extended to melanoma and head and neck cancer. The upcoming results will help clarify whether this postbiotic approach can support gut barrier function and potentially enhance anticancer therapies.