Vitamin B6 Ameliorates Lipopolysaccharide‐Induced Inflammation in Mouse Gastric Organoids

Gastric mucosal inflammation is a critical precondition of various gastric diseases, and development of safe and effective anti-inflammatory agents for prompt resolution of acute inflammation at early stage is vital to preventive medicine. B vitamins are essential water-soluble nutrients with reported anti-inflammatory properties, yet their potent regulatory effects in gastric mucosal inflammation are not systemically assessed. In this study, we adopted a lipopolysaccharide (LPS)-induced inflammatory mouse gastric organoid model to screen for anti-inflammatory B vitamin family members. With the anti-inflammatory effect of vitamin B12 (VB12) being validated in this gastric organoid model, which is consistent with the roles in other biological settings, further screening of the rest B vitamin members identified vitamin B6 (VB6) as the most potent anti-inflammatory agent as it preventatively ameliorated LPS-induced organoid collapse and preserved gastric epithelial polarity in the inflammatory organoids. Functional assays confirmed that VB6 significantly downregulated the expressions of key pro-inflammatory Tnf, Cxcl1, and Il1b genes, and inhibited TNF-α and IL-1β protein secretions. Further mechanistic exploration revealed that VB6 antagonized LPS-induced inflammatory responses by targeting the transcription of positive regulatory genes in core LPS-mediated inflammatory signaling pathways. These findings provide important experimental evidence for the development of nutrition-based intervention strategies for gastric inflammatory diseases in human.