2025/11/21 by Cristina Rosell‐Cardona, Emily G. Knox, Paula Sánchez-Díaz +8 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Barrier Structure and Function Studies #Gut microbiota and health #Tryptophan and brain disorders
paper · doi:10.1016/j.nsa.2025.106876
openalex publication_date 2025/11/21 · openalex created_date 2025/11/23 · openalex updated_date 2026/08/01
The gut microbiota influences brain function via the gut-brain axis, but the underlying molecular processes remain unclear. Critical to this communication are barrier systems, such as epithelial gut and the blood-brain barrier, which mediate the interface between circulating signals and gut-brain communication. Microbial metabolites are key mediators of the gut microbiota that can influence barrier integrity. In this study, we used well-established in vitro models of the blood–brain and gut barriers and exposed them to a wide range of physiologically relevant stress-associated microbial metabolites, including tryptophan-derived metabolites with and without lipopolysaccharide (LPS) as a disrupting insult. We demonstrated that indole, indole-3-acetate, indole-3-propionate and tryptamine can modulate both gut and brain barriers in a dose- and cell-type dependent manner. Our findings suggest that specific indole metabolites should be further evaluated as promising novel therapeutic interventions to regulate barrier integrity along the microbiota-gut-brain axis.