Xenobiotic-induced ribosomal stress compromises dysbiotic gut barrier aging: A one health perspective

Upon exposure to internal or environmental insults, ribosomes stand sentinel. In particular, stress-driven dys-regulation of ribosomal homeostasis is a potent trigger of adverse outcomes in mammalians. The present study assessed whether the ribosomal insult affects the aging process via the regulation of sentinel organs such as the gut. Analyses of the human aging dataset demonstrated that elevated features of ribosomal stress are inversely linked to barrier maintenance biomarkers during the aging process. Ribosome-insulted worms displayed reduced lifespan, which was associated with the disruption of gut barriers. Mechanistically, ribosomal stress-activated Sek-1/p38 signaling, a central platform of ribosomal stress responses, counteracted the gut barrier deteriora-tion through the maintenance of the gut barrier, which was consistent with the results in a murine insult model. However, since the gut-protective p38 signaling was attenuated with aging, the ribosomal stress-induced distress was exacerbated in the gut epithelia and mucosa of the aged animals, subsequently leading to increased bacterial exposure. Moreover, the bacterial community-based evaluation predicted concomitant increases in the abun-dance of mucosal sugar utilizers and mucin metabolic enzymes in response to ribosomal insult in the aged host. All of the present evidence on ribosomal insulting against the gut barrier integrity from worms to mammals provides new insights into organelle-associated translational modulation of biological longevity in a one health perspective.

Automated summary

This study investigates the impact of ribosomal insult on gut health and reveals that ribosomal insult leads to gut barrier disruption and accelerates the aging process. Activation of the Sek-1/p38 signaling pathway can mitigate the gut barrier damage caused by ribosomal insult, thus delaying the aging process. The study also demonstrates that ribosomal insult results in dysbiosis of the gut microbiota and increases the risk of bacterial exposure.