The intestine is a key organ for the absorption of amino acids. L-theanine (LTA) is a structural analog of glutamine and a characteristic non-protein amino acid found in tea (Camellia sinensis) that regulates lipid and protein metabolism. The present study explored the role of LTA in intestinal amino acid absorption, protein synthesis, and its mechanisms. Overall, our findings suggest that LTA supplementation not only affects serum alkaline phosphatase (AKP), total protein (TP), and urea nitrogen (BUN) levels, but it also upregulates the mRNA and protein expression of amino acid transporters (EAAT3, EAAT1, 4F2hc, y⁺LAT1, CAT1, ASCT2, and B⁰AT1), and activates the mTOR signaling pathway. The downstream S6 and S6K1 proteins are regulated, and the expression of amino acid transporters is regulated. These findings suggest that LTA increases intestinal AA absorption, promotes protein metabolism, and increases nitrogen utilization by upregulating AAT expression, activating the mTOR signaling pathway, and phosphorylating the mTOR downstream proteins S6 and S6K1.

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.

Background: Chronic alcohol intake impairs intestinal function, while L-theanine (LTA) may support intestinal health. However, the protective effects of LTA to chronic alcoholic intestinal injuries remain unclear. Methods: SD rats were administered LTA for 8 weeks and then co-administered Lieber–DeCarli liquid alcohol feed and LTA for 4 weeks to establish a chronic alcoholic intestinal injury model and investigate the mitigating influence of LTA on chronic alcoholic intestinal injury. Results: LTA alleviated duodenal pathology and intestinal permeability injury and reduced intestinal oxidative stress and inflammatory response, thereby mitigating chronic alcoholic intestinal injury. Additionally, LTA ameliorated disturbances in the gut microbiota induced by chronic alcohol intake by increasing the beneficial bacteria abundance (Ruminococcus and Odoribacter) and decreasing the harmful bacteria abundance (Enterococcus). Moreover, LTA altered the metabolic profiles associated with ethanol and linoleic (LA) and arachidonic acid (AA) metabolism. ADH6, ALDH2, and ACSS1 mRNA and protein levels were upregulated by LTA, whereas those for CYP2E1, FADS2, ALOX-5, and COX-1 were downregulated. Concurrently, LTA increased the levels of metabolites, such as acetyl-CoA, and decreased the levels of ethanol, acetaldehyde, acetic acid, LA, AA, PGE2, 13-HPODE, and LTB4. Conclusions: L-theanine mitigates chronic alcoholic intestinal injury by regulating intestinal alcohol and LA-AA metabolism. Our findings support the functional potential of the dietary supplement LTA and highlight its potential for addressing chronic intestinal injury caused by chronic alcohol intake.