Siraitiae Fructus ameliorates allergic asthma via "gut-lung axis" modulation: Th17/Treg ratio rebalancing, TLR4/MyD88/NF-κB pathway suppression, and T lymphocytes migration inhibition.

Siraitiae Fructus (SF), a well-known medicinal and edible herb, is commonly employed for management of respiratory discomfort. Previous study has demonstrated that Siraitiae Fructus total saponins (SFTS) served as the effective components of SF. However, the underlying mechanisms of these effects remain incompletely understood. To evaluate the effects of SFTS and its primary constituent, Mogroside V (MV), an ovalbumin (OVA)-induced allergic asthma model was established. Histopathological analysis, flow cytometry, 16S rRNA sequencing, short-chain fatty acids (SCFAs) quantification, and western blotting were employed to characterize pulmonary and intestinal alterations, immune modulation, and associated pathways. SFTS administration significantly alleviated airway inflammation and attenuated lung tissue damage. These effects were associated with a marked modulation of gut microbiota composition, a significant increase in serum levels of propionic and butyric acids (P < 0.05), and a restoration of the Th1/Th2 and Th17/Treg immune balances. Mechanistically, SFTS was found to suppress the TLR4/MyD88/NF-κB signaling pathway in lung and intestinal tissues and inhibit the migration of Th2 and Th17 cells (P < 0.05). Notably, SFTS demonstrated a more comprehensive regulatory capacity than MV. In summary, these findings indicated that SFTS alleviates allergic asthma by regulating the gut microbiota-SCFAs-Th17/Treg axis and inhibiting TLR4/MyD88/NF-κB pathway. This study not only provides scientific evidence for the traditional use of SF in treating respiratory disorders but also identifies SFTS as a potential immunomodulator for allergic asthma via the "gut-lung axis".