Clinical evidence for microbial-derived polyphenol metabolites in health and disease: a scoping review

Growing translational evidence indicates that the physiologically relevant effects of dietary (poly)phenols are largely mediated by gut microbial metabolism, resulting in bioactive microbial-derived (poly)phenol metabolites (MPMs). However, clinical evidence linking specific MPMs to defined health outcomes has not been comprehensively synthesized.

This scoping review characterizes clinical studies assessing associations between MPMs and human health and disease.

We systematically searched MEDLINE (PubMed), Embase (Elsevier), Web of Science (SCIE, ESCI), Scopus, ProQuest Health and Medical, the Cochrane Library, and ClinicalTrials.gov. Eligible studies quantified specific MPMs (e.g., urolithins, phenolic acids) in human biological specimens and assessed associations with biological or clinical outcomes. Two reviewers independently screened and extracted data using standardized forms. Findings were synthesized qualitatively.

Seventy studies across cardiometabolic, inflammatory/oxidative stress, neurological, gastrointestinal, cancer, musculoskeletal, epigenetic, and respiratory domains were included. Evidence was most concentrated in cardiometabolic outcomes (n = 38), with recurrent associations involving urolithins and phenolic acid derivatives. This was followed by inflammatory/oxidative stress (n = 15) and neurological outcomes (n = 11). Musculoskeletal, epigenetic, and respiratory outcomes were least represented. Substantial heterogeneity in study design, metabolite measurement, and outcome reporting limited cross-study comparability.

Specific MPMs may contribute to inter-individual variability in diet-related health responses. Standardized metabolite assessment and prospective trials evaluating direct supplementation of specific microbial metabolites, particularly in individuals with limited systemic exposure, are needed to clarify their role in human health and inform precision nutrition strategies.