Psychobiotics and polyphenols modulate the gut-brain axis through personalized nutritional strategies in mental health

Anxiety and depression are major contributors to the global disease burden; however, fewer than half of patients treated with standard pharmacotherapy achieve sustained remission. This gap underscores the need to identify effective adjunctive treatments. The bidirectional gut-brain axis offers a valuable perspective by linking diet to neurotransmission, neuroinflammation, and hypothalamic-pituitary-adrenal (HPA) axis reactivity. This framework positions nutritional psychiatry as a complement, rather than a substitute, for established care. This narrative review examines three converging intervention classes: psychobiotics, dietary polyphenols, and precision nutraceuticals. Randomized trials of Lactobacillus helveticus R0052, Bifidobacterium longum R0175, and Lactiplantibacillus plantarum PS128 demonstrate modest but reproducible reductions in depressive and anxiety symptoms, although effect sizes vary. Plausible mechanisms include reduced low-grade neuroinflammation, partial normalization of HPA axis reactivity, and a shift in tryptophan metabolism from the kynurenine pathway toward serotonin synthesis—although human evidence supporting these pathways remains limited. Polyphenol biology introduces an additional dimension. Microbial conversion of ellagitannins, isoflavones, and lignans into urolithin A, equol, and enterolactone can alter the bioavailability of neuroactive metabolites. Consequently, an individual’s metabotype likely accounts for some of the variability in clinical response. We propose that microbiota-guided strategies—stratified by enterotype, metabotype, tryptophan–kynurenine flux, and short-chain fatty acid output—could significantly enhance psychiatric care. Multi-omic profiling and artificial intelligence (AI)-driven digital phenotyping can operationalize this precision approach. However, methodological heterogeneity, small sample sizes, inconsistent strain and dose reporting, and regulatory ambiguity continue to hinder translation, as recent meta-analyses highlight.