Pentagalloylglucose, a limited oral bioavailability polyphenol, improves allergic asthma through regulating gut...

Pentagalloylglucose (PGG), a natural hydrolysable gall tannin, has limited bioavailability, and its biological activities are concentrated in the digestive system. However, our study discovered that this nonabsorbable compound can improve allergic asthma. This study focuses on elucidating the mechanisms underlying PGG's anti-allergic asthma effects.

PGG serum metabolites were analyzed by UPLC/Q-TOF MS. To further explore its mechanisms, 16S rRNA sequencing, qPCR, and UPLC/Q-TOF MS were used to assess gut microbiota and metabolites. Fecal microbiota transplantation from PGG-treated mice into antibiotic-treated asthmatic mice evaluated its microbiota-dependent effects. Flow cytometry analyzed PGG's modulation of pulmonary ILC2s in a murine asthma‑colitis comorbid model.

PGG's serum metabolites were below the quantification limit. PGG administration improved colonic injury and modulated L. reuteri; notably, exogenous L. reuteri alleviated asthma via increasing I3A from Trp metabolism. However, fecal microbiota transplantation from PGG-treated mice did not alleviate asthma, and PGG remained effective in microbiota-depleted mice, suggesting its action is microbiota-independent. Furthermore, PGG alleviated intestinal inflammation in both normal and antibiotic-treated asthmatic mice. In a comorbid colitis-asthma model, PGG counteracted colitis-aggravated asthma symptoms by modulating lung ILC2s.

Although PGG modulates the gut microbiota and related metabolites, its anti-asthmatic effect is not primarily dependent on this pathway. Notably, it can ameliorate lung ILC2 dysregulation by alleviating enteritis.