Topic: Gut–Brain Axis Mechanisms in Health and Disease: From Microbial Metabolites to Neural Circuitry

The gut–brain axis is increasingly recognized as a complex, bidirectional communication network in which the intestinal microbiome serves as a central metabolic and ecological driver of host physiology. Rather than acting as a passive correlate of neurological outcomes, gut microbial communities produce a diverse repertoire of bioactive metabolites that shape neuroimmune, endocrine, and neuronal signalling pathways. These microbiome-derived metabolites, including short-chain fatty acids, indole derivatives, bile acid metabolites, and tryptophan catabolites, constitaaute key functional effectors linking microbial metabolism to host gut and brain function within the microbiome-gut-brain axis framework.

Over the past decade, the field has shifted from descriptive microbiome-brain associations toward mechanistic frameworks that define how microbial metabolic activity regulates blood-brain barrier integrity, neuroimmune signaling, synaptic organization, and neuronal excitability. Emerging evidence further positions the gut microbiome as a dynamic metabolic hub integrating environmental and host-derived inputs, with signaling transmitted to the central nervous system via coordinated vagal, immune, and endocrine pathways. This Special Issue aims to highlight cutting-edge research that places microbial metabolism at the core of gut-brain communication, emphasizing mechanistic insight and systems-level integration across health and disease.

Topics of interest include, but are not limited to:

● Microbiome-derived metabolites regulating neural and glial function;

● Gut microbiome control of microglial states and neuroimmune signaling;

● Microbiome-blood-brain barrier interactions as dynamic regulatory interfaces;

● Microbiota-driven vagal and neuroendocrine pathways in gut-brain communication;

● Microbial regulation of neural circuit development and synaptic plasticity;

● Multi-omics and systems biology approaches to microbiome–brain mechanisms.

Gut–brain axis, microbiome, microbial metabolites, neuroimmune signaling, blood–brain barrier, microglia, synaptic plasticity, microbial ecology, multi-omics