Lacticaseibacillus rhamnosus GG-driven remodeling of arginine metabolism mitigates gut barrier dysfunction
Issued Date
2025-07-01
Resource Type
ISSN
01931857
eISSN
15221547
Scopus ID
2-s2.0-105008738744
Pubmed ID
40418622
Journal Title
American Journal of Physiology Gastrointestinal and Liver Physiology
Volume
329
Issue
1
Start Page
G162
End Page
G185
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Physiology Gastrointestinal and Liver Physiology Vol.329 No.1 (2025) , G162-G185
Suggested Citation
Antonio J.M., Liu Y., Suntornsaratoon P., Jones A., Ambat J., Bala A., Kanattu J.J., Flores J., Bandyopadhyay S., Upadhyay R., Bhupana J.N., Su X., Li W.V., Gao N., Ferraris R.P. Lacticaseibacillus rhamnosus GG-driven remodeling of arginine metabolism mitigates gut barrier dysfunction. American Journal of Physiology Gastrointestinal and Liver Physiology Vol.329 No.1 (2025) , G162-G185. G185. doi:10.1152/ajpgi.00366.2024 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110971
Title
Lacticaseibacillus rhamnosus GG-driven remodeling of arginine metabolism mitigates gut barrier dysfunction
Corresponding Author(s)
Other Contributor(s)
Abstract
Inflammatory bowel diseases (IBDs) and gut barrier impairment are associated with changes in dietary tryptophan and arginine metabolism, but mechanisms of barrier perturbation and restoration are unclear. We show here that the widely consumed probiotic Lacticaseibacillus rhamnosus GG (LGG) enhances gut barrier functions in part through stimulating the intestinal arginine metabolic pathway, and this mechanism depends on the sufficiency of dietary tryptophan in the host. Specifically, LGG markedly upregulates argininosuccinate lyase (ASL), the enzyme that breaks down argininosuccinate into arginine. ASL expression is markedly reduced during experimental colitis with an accumulation of serum argininosuccinate. LGG colonization in mice reduces serum argininosuccinate, a metabolite that inversely correlates with tight junction gene expression, impairs barrier function, and exacerbates dextran sodium sulfate colitis. We show that LGG-derived indoles as well as arginine metabolites enhanced argininosuccinate lyase (ASL) and nitric oxide synthase (NOS2) expression, linking microbial metabolism to nitric oxide production and epithelial homeostasis. Patients with IBD have increased ASS1 and decreased ASL expression, suggesting a metabolic bottleneck driving ASA accumulation. We propose that signaling pathways underlying LGG and tryptophan-mediated ASL upregulation can be useful therapeutic targets to normalize arginine metabolism in select patients with IBD.