胱硫醚 γ-裂解酶 (CTH) 是逆转硫途径中的关键酶，逆转硫途径是含硫氨基酸代谢的主要途径，特别是将胱硫醚转化为半胱氨酸。我们报道 CTH 支持由病原体幽门螺杆菌引起的胃炎。在此，我们的目的是研究 CTH 在结肠炎症中的作用。首先，我们发现在右旋糖酐硫酸钠诱导的结肠炎小鼠的结肠粘膜中诱导了CTH。 Cth-/-小鼠的结肠中完全不表达CTH。我们观察到，与野生型动物相比，Cth 缺陷小鼠的临床和组织学参数有所改善。然而，Cth 缺失对用氧化偶氮甲烷-DSS 治疗的小鼠的肿瘤发生和发育不良水平没有影响，作为结肠炎相关癌发生的可靠模型。从机制上讲，我们确定，编码溶质载体家族 7 成员 11（半胱氨酸阴离子形式的转运蛋白）的基因 Slc7a11 的缺失不会影响 DSS 结肠炎。最后，我们发现与 WT 和 Slc7a11-/- 小鼠相比，Cth-/- 小鼠粪便微生物群的丰富度和多样性显着增加。总之，我们的数据表明，CTH 酶代表了炎症性肠病患者临床干预的目标，可能通过有益地重塑肠道微生物群的组成来实现。© 2024。这是美国政府的作品，不受版权保护。我们;可能适用外国版权保护。

Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth-/- mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth-/- mice compared to both WT and Slc7a11-/- mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota.© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.