Flavonoids as functional food-derived modulators of the gut microbiota-NF-κB axis in metabolic dysfunction-associated...

Metabolically Dysfunctional-Associated Steatotic Liver Disease (MASLD) is increasingly recognised as a gut-liver axis disorder driven by sustained activation of pro-inflammatory signalling networks, particularly the NF-κB pathway. Flavonoids, a diverse class of dietary polyphenols, have emerged as promising modulators of NF-κB-mediated gut-liver crosstalk due to their capacity to restore intestinal homeostasis and suppress hepatic inflammation. This review synthesises recent preclinical evidence identifying NF-κB as a central mechanistic target underlying flavonoid actions in MASLD. A structured literature search was conducted in PubMed, Scopus, Web of Science, and ScienceDirect to identify studies published between 2020 and February 2026. Accumulating evidence indicates that flavonoids remodel the gut microbiota toward beneficial taxa. Several flavonoids also modulate upstream regulators, thereby converging on NF-κB to mitigate MASLD. To improve translational interpretation, animal experimental doses were contextualised using established human-equivalent dose conversion methods, alongside reported dietary sources and estimated achievable intake levels. Although the present work highlights the considerable potential of flavonoids as functional food-derived modulators of the gut microbiota NF-κB axis in MASLD, their clinical translation remains constrained by limited bioavailability and heterogeneity across experimental models, highlighting the need for standardised dosing strategies, integrated host microbiota analyses, and well-designed human studies to substantiate clinical applicability.