Uncovering gut-bacterial chemical signaling that modulates neuronal function

Growing evidence highlights the gut microbiome as a key regulator of brain health through the gut-brain axis, a bidirectional communication network linking intestinal microbes with neuronal function. Age-associated shifts in host metabolism are accompanied by alterations in gut microbial composition and activity, leading to changes in microbial metabolites, neurotransmitter-like compounds, and immunomodulatory molecules. Reduced production of microbial short-chain fatty acids (SCFAs) has been associated with compromised blood–brain barrier integrity and increased vulnerability to neuroinflammation and neurodegeneration. However, the specific bacterial metabolites and signalling pathways that directly modulate neuronal function remain largely unknown, with most current evidence remaining correlative. My PhD work aims to uncover gut-bacterial chemical signals that influence neuronal physiology and contribute to brain health or age-associated disease. By integrating microbiology, neuroscience, metabolomics, and computational analysis, my project seeks to systematically identify neuroactive microbial molecules and their producing organisms. A high-throughput, bottom-up experimental framework will be employed, in which exometabolomes derived from individual bacterial cultures and synthetically assembled microbial communities are screened for effects on neuronal cells. Metabolomic profiling of bioactive fractions will then be used to identify the compounds responsible for observed neuroprotective or neuroactive effects. This approach enables a mechanistic link between specific gut bacteria, their secreted metabolites, and neuronal responses. Ultimately, this project will advance our understanding of gut-derived chemical signaling in the regulation of neuronal function and may uncover novel microbial and metabolic targets for therapeutic intervention in neurodegenerative and age-associated disorders.

PhD start: 09/14/2023