L-Theanine Mitigates Acute Alcoholic Intestinal Injury by Activating the HIF-1 Signaling Pathway to Regulate the TLR4/NF-κB/HIF-1α Axis in Mice.

BACKGROUND/OBJECTIVES: Acute alcohol consumption can cause intestinal dysfunction, whereas L-theanine (LTA) has shown the potential to support intestinal health. We explored L-theanine's ability to protect against acute alcohol-induced injury. METHODS: Male C57BL/6 mice were administered LTA for 28 d and then underwent acute alcohol intestinal injury modeling for 8 days. RESULTS: The results revealed that LTA ameliorated alcohol-induced pathological damage in the duodenum and gut permeability, improved secretory immunoglobulin A (SIgA) content, and reduced oxidative stress, inflammatory markers, and serum lipopolysaccharide (LPS) content in mice. Furthermore, LTA restored the composition of the intestinal flora, increasing the abundance of Alloprevotella, Candidatus_Saccharimonas, Muribaculum, and Prevotellaceae_UCG-001. Additionally, LTA increased beneficial metabolites, such as oxyglutaric acid and L-ascorbic acid, in the HIF-1 pathway within the enrichment pathway. Further investigation into the HIF-1 signaling pathway identified up-regulation of claudin-1, HIF-1α, occludin, and ZO-1, and down-regulation of TLR4, PHD2, p65 NF-κB, TNF-α, and IFN-γ mRNA and protein levels. CONCLUSIONS: These results suggest that LTA may enhance the intestinal barrier by activating the HIF-1 signaling pathway to regulate the TLR4/NF-κB/HIF-1α axis, thereby reducing acute alcoholic intestinal injury.