Riboflavin Bioenriched Soymilk Alleviates Oxidative Stress Mediated Liver Injury, Intestinal Inflammation, and Gut Microbiota Modification in B₂ Depletion–Repletion Mice

Epidemiological evidence emphasizes that ariboflavinosis can lead to oxidative stress, which in turn may mediate the initiation and progression of liver injury and intestinal inflammation. Although vitamin B₂ has gained worldwide attention for its antioxidant defense, the relationship between B₂ status, oxidative stress, inflammatory response, and intestinal homeostasis remains indistinct. Herein, we developed a B₂ depletion–repletion BALB/c mice model to investigate the ameliorative effects of B₂ bioenriched fermented soymilk (B₂FS) on ariboflavinosis, accompanied by oxidative stress, inflammation, and gut microbiota modulation in response to B₂ deficiency. In vivo results revealed that the phenotypic ariboflavinosis symptoms, growth rate, EGRAC status, and hepatic function reverted to normal after B₂FS supplementation. B₂FS significantly elevated CAT, SOD, T-AOC, and compromised MDA levels in the serum, simultaneously up-regulated Nrf2, CAT, and SOD2, and down-regulated Keap1 gene in the colon. The histopathological characteristics revealed significant alleviation in the liver and intestinal inflammation, confirmed by the downregulation of inflammatory (IL-1β and IL-6) and nuclear transcription (NF-κB) factors after B₂FS supplementation. B₂FS also increased the abundance and diversity of gut microbiota, increased the relative abundance of Prevotella and Absiella, as well as decreased Proteobacteria, Fusobacteria, Synergistetes, and Cyanobacteria in strong conjunction with antioxidant, anti-inflammatory properties, and gut homeostasis along with the remarkable increase in cecal SCFAs content. We hereby reveal that B₂FS can effectively alleviate deleterious ariboflavinosis associated with oxidative stress mediated liver injury, chronic intestinal inflammation, and gut dysbiosis in the B₂ depletion–repletion mice model via activation of the Nrf2 signaling pathway.