Lactobacillus Salivarius-Derived Indole-3-Acetic Acid Promotes AHR-PARP1 Axis-Mediated DNA Repair to Mitigate Intestinal Aging.
- 2025-10-28
- Advanced science (Weinheim, Baden-Wurttemberg, Germany) 13(4)
- PubMed: 41147383
- DOI: 10.1002/advs.202515794
Study Design
- Population
- aged humans and mice
- Methods
- intestinal AHR activation by indole-3-acetic acid (IAA), derived from Lactobacillus salivarius rather than host cells; in vivo and in vitro experiments, including intestine-specific Ahr knockout mice, Ahr and Parp1 knockdown, and Parp1 overexpression in enterocytes
Increasing evidence suggests that the aryl hydrocarbon receptor (AHR) and poly (ADP-ribose) polymerase 1 (PARP1) are closely linked to aging and aging-related disorders. However, the underlying mechanisms of AHR-PARP1 axis-mediated DNA repair in countering aging remain largely unknown. In this study, it is found that both aged humans and mice exhibit marked intestinal aging, characterized by gut dysbiosis and dysfunction and DNA damage, compared to their young counterparts. Intriguingly, it is discovered that intestinal AHR activation by indole-3-acetic acid (IAA), which is derived from Lactobacillus salivarius rather than host cells, effectively mitigates intestinal aging by regulating DNA-damage responses. Mechanistically, activated AHR by IAA interacts with PARP1, potentiating PARP1 activity and the polymerization of poly (ADP-ribose) (PARylation) by binding to its promoter. This interaction enhances intestinal barrier function and suppresses inflammation and cell senescence. Finally, the interplay between AHR and PARP1 is confirmed by in vivo and in vitro experiments, including intestine-specific Ahr knockout mice, Ahr and Parp1 knockdown, and Parp1 overexpression in enterocytes. These findings provide a potential intervention strategy targeting AHR-PARP1 axis to mitigate age-related intestinal dysfunction.
Research Insights
| Supplement | Dose | Health Outcome | Effect Type | Effect Size | Source |
|---|---|---|---|---|---|
| Lactobacillus salivarius LS-33 | — | Enhanced DNA Repair | Beneficial | Moderate | View sourceactivated AHR by IAA interacts with PARP1, potentiating PARP1 activity and the polymerization of poly (ADP-ribose) (PARylation) by binding to its promoter. |
| Lactobacillus salivarius LS-33 | — | Improved Intestinal Barrier Function | Beneficial | Moderate | View sourceThis interaction enhances intestinal barrier function and suppresses inflammation and cell senescence. |
| Lactobacillus salivarius LS-33 | — | Reduced Cellular Senescence | Beneficial | Moderate | View sourceThis interaction enhances intestinal barrier function and suppresses inflammation and cell senescence. |
| Lactobacillus salivarius LS-33 | — | Reduced Inflammation | Beneficial | Moderate | View sourceThis interaction enhances intestinal barrier function and suppresses inflammation and cell senescence. |
| Lactobacillus salivarius LS-33 | — | Reduced Intestinal Aging | Beneficial | Moderate | View sourceintestinal AHR activation by indole-3-acetic acid (IAA), which is derived from Lactobacillus salivarius rather than host cells, effectively mitigates intestinal aging by regulating DNA-damage responses |