Diet, mycobiome and virome: from mucosal immunity to gut-brain axis regulation

The gut microbiota plays a central role in regulating host metabolism, immune function and gut-brain axis signaling. Although bacterial communities have dominated microbiome research, the intestinal ecosystem also encompasses fungal communities and bacteriophages that can influence microbial functions and host physiology. This review examines how interactions among the mycobiome, virome (principally bacteriophages), and the bacterial microbiota shape metabolic signaling pathways relevant to gut-brain axis regulation. Fungal-bacterial and phage-bacterial interactions can remodel bacterial community function through ecological competition, biofilm formation, prophage induction and horizontal gene transfer. These multi-kingdom interactions modulate key microbial metabolites, including short-chain fatty acids, tryptophan-derived indole metabolites and bile acid intermediates, which act as major regulators of intestinal barrier integrity, immune responses and neuroimmune signaling. Disruption of these metabolic pathways may contribute to altered host signaling through receptors such as the aryl hydrocarbon receptor (AhR) and bile acid receptors, with downstream effects on intestinal inflammation and neuroimmune regulation. Diet is among the most influential determinants of this ecosystem, directly shaping microbiota bacterial metabolism, fungal growth and phage-bacteria interactions. Dietary patterns rich in fermentable fibers and bioactive compounds may promote beneficial microbial metabolic outputs, whereas Western-type diets and high sugar intake may favor ecological imbalances that disrupt microbial signaling pathways relevant to gut-brain axis regulation.