Combined neuroprotective effects of vitamins B2 and B3 on LPS-induced neuroinflammation: a multi-omics insight into the gut-brain axis

Neuroinflammation serves as a pivotal pathological driver of cognitive decline, and dietary modulation targeting the gut-brain axis is regarded as a potential and safe therapeutic strategy. Herein, we investigated the combined neuroprotective effects of riboflavin (vitamin B2) and nicotinamide (vitamin B3) in an LPS-induced neuroinflammatory mouse model. Integrative analyses encompassing behavioral assessment, histopathology, 16S rRNA sequencing and untargeted metabolomics were performed to explore underlying mechanisms. Combined B2/B3 intervention markedly alleviated anxiety-like behaviors and spatial memory impairment. Mechanistically, it restrained hippocampal neuroinflammation and oxidative stress, which was closely associated with the modulation of the Sirt1/NF-κB pathway and inhibiting glial overactivation. Furthermore, B2/B3 supplementation reshaped gut microbiota dysbiosis by enriching Akkermansia and reducing Desulfovibrio , and restored metabolic homeostasis by modulating neuroprotective metabolites. To the best of our knowledge, few studies have demonstrated that B2 and B3 exert combined neuroprotection via remodeling the gut microbiota–metabolite network, providing a scientific basis for their application as functional food ingredients against neuroinflammation.