Lactobacillus rhamnosus GG Stimulates Dietary Tryptophan-Dependent Production of Barrier-Protecting Methylnicotinamide.
| Autor: | Suntornsaratoon P; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand., Antonio JM; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey., Flores J; Department of Biological Sciences, Rutgers University, Newark, New Jersey., Upadhyay R; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey., Veltri J; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey., Bandyopadhyay S; Department of Biological Sciences, Rutgers University, Newark, New Jersey., Dadala R; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey., Kim M; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey., Liu Y; Department of Biological Sciences, Rutgers University, Newark, New Jersey., Balasubramanian I; Department of Biological Sciences, Rutgers University, Newark, New Jersey., Turner JR; Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Su X; Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey., Li WV; Department of Statistics, University of California, Riverside, Riverside, California., Gao N; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey; Department of Biological Sciences, Rutgers University, Newark, New Jersey. Electronic address: ngao@newark.rutgers.edu., Ferraris RP; Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, New Jersey. Electronic address: ferraris@njms.rutgers.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2024; Vol. 18 (2), pp. 101346. Date of Electronic Publication: 2024 Apr 18. |
| DOI: | 10.1016/j.jcmgh.2024.04.003 |
| Abstrakt: | Background & Aims: Lacticaseibacillus rhamnosus GG (LGG) is the world's most consumed probiotic but its mechanism of action on intestinal permeability and differentiation along with its interactions with an essential source of signaling metabolites, dietary tryptophan (trp), are unclear. Methods: Untargeted metabolomic and transcriptomic analyses were performed in LGG monocolonized germ-free mice fed trp-free or -sufficient diets. LGG-derived metabolites were profiled in vitro under anaerobic and aerobic conditions. Multiomic correlations using a newly developed algorithm discovered novel metabolites tightly linked to tight junction and cell differentiation genes whose abundances were regulated by LGG and dietary trp. Barrier-modulation by these metabolites were functionally tested in Caco2 cells, mouse enteroids, and dextran sulfate sodium experimental colitis. The contribution of these metabolites to barrier protection is delineated at specific tight junction proteins and enterocyte-promoting factors with gain and loss of function approaches. Results: LGG, strictly with dietary trp, promotes the enterocyte program and expression of tight junction genes, particularly Ocln. Functional evaluations of fecal and serum metabolites synergistically stimulated by LGG and trp revealed a novel vitamin B Conclusions: Our study uncovers a novel LGG-regulated dietary trp-dependent production of MNA that protects the gut barrier against colitis. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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