The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice.

Autor: Gobert AP; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Latour YL; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., McNamara KM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Hawkins CV; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Williams KJ; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Asim M; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Barry DP; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Allaman MM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Delgado AG; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Milne GL; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Zhao S; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Piazuelo MB; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Washington MK; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Coburn LA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, 37232, USA., Wilson KT; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. keith.wilson@vumc.org.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. keith.wilson@vumc.org.; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. keith.wilson@vumc.org.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. keith.wilson@vumc.org.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, 37232, USA. keith.wilson@vumc.org.
Jazyk: angličtina
Zdroj: Amino acids [Amino Acids] 2024 Oct 19; Vol. 56 (1), pp. 63. Date of Electronic Publication: 2024 Oct 19.
DOI: 10.1007/s00726-024-03423-4
Abstrakt: 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.)
Databáze: MEDLINE
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