IDDF2022-ABS-0210 The role and mechanism of leucine in mucosal healing of ulcerative colitis. (2nd September 2022)

• Record Type: Journal Article
• Authors: Wu, Jing; Li, Maojuan; Zhou, Chan; Niu, Junkun
• Is Part Of: Gut. Volume 71(2022)Supplement 2
• Page Start: A58
• Page End: A58
• Publication Date: 2022-09-02
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2022-IDDF.65
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background: Leucine (Leu) plays an important role in the enterocyte. Our previous study showed that fecal concentration of Leu was decreased after mucosal healing (MH) of UC, but the mechanism of Leu in MH remains unknown. Methods: The receiver operator characteristic curve was plotted to evaluate the value of Leu in predicting MH, combined with Fecal calprotectin (FC). A dextran sulfate sodium-induced colitis model was established by feeding a leucine-deficient and complete amino acid diet to explore the role of Leu in the intestinal barrier. Cell proliferation, migration, apoptosis and the expressions of NF-κB, TJ and mTORC1signal proteins were detected in Caco-2 cultured by deficient and 250μmol/L Leu. Results: 1. Fecal concentration of Leu was positively correlated with FC, R=0.831. The AUC of Leu in predicting of MH was 0.9289, and the sensitivity and specificity were 86.7% and 93.3% when the cut-off value was 347.35μg/g. 2. The biosynthesis of Leu was enriched in MH, related to Bacteroidetes, Ruminococcus, Eubacterium, Alistipes and Faecalibacterium prausnitzii. 3. The expression of Claudin-4, Occludin and ZO-1 decreased in mice fed a Leu-deficient diet, and increased after supplementation of Leu. The inflammation exhibited the opposite effect. 4. In Leu deficient cells, the proliferation and migration activity decreased, accompanied by a little apoptosis. The expressions of TLR4, MyD88, and p-P65 were increased, while Claudin-4, Occludin, ZO-1, p-mTORC1, p-S6K and p-4E-BP1 decreased. The changes were more pronounced after LPS. Inhibited mTORC1, proliferation and migration activity of cells decreased, apoptosis and the expressions of TLR4, MyD88, and p-P65 were increased, while the expressions of Claudin-4, Occludin, ZO-1, p-S6K and p-4E-BP1 were decreased. Conclusions: 1. Leu had high sensitivity and specificity in predicting MH, and had the potential to become a novel adjuvant biomarker for MH. 2. The biosynthesis of Leu was enriched in MH, which may affect the gut microbiota, and participated in intestinal epithelial metabolism to promote MH. 3. Leu promoted cell proliferation, migration, and anti-apoptosis, inhibited NF-κB pathway to anti-inflammatory and stimulated protein synthesis to enhance intestinal barrier function by activating mTORC1 signaling pathway, participated in MH.