| Title: |
Biofilm state Limosilactobacillus reuteri modulates aryl hydrocarbon receptor activity and suppresses experimental necrotizing enterocolitis |
| Authors: |
Sajankila, Nitin; Dumbauld, Zachary; Wang, Yijie; Wala, Samantha J.; Ragan, Mecklin V.; Al-Hadidi, Ameer; Volpe, Samuel G.; Wickham, Joseph; Mashburn-Warren, Lauren; Wayne, Colton; Jacobs, Taylor; Narayanan, Siddharth; Bailey, Michael T.; Goodman, Steven D.; Besner, Gail E.; Mihi, Belgacem |
| Contributors: |
Advanced Research Training in Immunology for Surgery Trainees; Trainee Research Fellowship Award for Basic Science/Translational Research |
| Source: |
Pediatric Research ; ISSN 0031-3998 1530-0447 |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2025 |
| Description: |
Background Decreased Aryl Hydrocarbon Receptor (AHR) signaling pathway activation is implicated in necrotizing enterocolitis (NEC) pathogenesis. Limosilactobacillus reuteri ( Lr ) is a probiotic that catabolizes tryptophan into AHR ligands. We have previously shown that Lr in its biofilm state has improved efficacy against NEC. However, the importance of the physiologic state of Lr (planktonic vs . biofilm) on AHR activation remains unknown. Methods In vitro experiments using intestinal epithelial cells (IEC) and in vivo experiments in premature rodents were carried out to assess the impact of planktonic- vs . biofilm-state Lr on AHR ligand production, AHR activation, and protection against NEC. Results Biofilm-state Lr was found to have increased persistence in the intestine of premature rodent pups compared to planktonic-state Lr . IECs exposed to conditioned media from Lr grown with tryptophan demonstrated increased AHR activation compared to IECs exposed to tryptophan alone. Finally, biofilm-state Lr was associated with increased intestinal AHR ligand production, AHR activation, and protection against NEC in rodent pups. Conclusion Biofilm-state Lr has increased persistence in the gut and protects against NEC. This protection is associated with increased AHR activation in the intestine. Through improved understanding of the interactions of Lr and AHR signaling, we may be able to further enhance Lr efficacy against NEC. Impact Limosilactobacillus reuteri in its biofilm state increases AHR activation and reduces intestinal injury during NEC. This is the first study to look at the role of the AHR signaling pathway in Limosilactobacillus reuteri -mediated protection against NEC. Development of an effective therapy to prevent NEC would reduce the morbidity and mortality of this lethal disease. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41390-025-04351-z |
| Availability: |
https://doi.org/10.1038/s41390-025-04351-z; https://www.nature.com/articles/s41390-025-04351-z.pdf; https://www.nature.com/articles/s41390-025-04351-z |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.3154ACA2 |
| Database: |
BASE |