Thymidine mitigates LPS-induced acute lung injury by regulating gut microbiota and metabolism through the lung-gut axis.

Abstract

Yam (Dioscorea opposita Thunb.) is a prominent traditional Chinese medicine with the core function of tonifying the lungs. Thymidine (Thy), a compound extracted from the stems and leaves of yam, has an unclear mechanism of action on acute lung injury (ALI). An ALI model was established by tracheal infusion LPS. Pulmonary edema, lung histopathology, lung function, oxidative stress, immunity, and inflammation of mice were detected. The analysis of metabolomics, intestinal flora, and lung PPAR-γ levels was to clarify the mechanism of Thy on ALI. The co-culture of Beas-2B and Caco-2 was used to investigate the effects of Thy combined with the PPAR-γ agonist rosiglitazone and antagonist T0070907 on the levels of PPAR-γ, oxidative stress, inflammation, and metabolites in LPS-induced cell model. Thy improved pulmonary edema and pathological damage in the lungs, reduced oxidative stress and immune inflammatory levels, and affected the balance of intestinal microbiota in ALI mice, as well as arachidonic acid metabolism, and regulated the levels of PPAR-γ. Under co-culture, Thy reduced oxidative stress levels in Beas-2B and Caco-2 and alleviated the levels of PPAR-γ, inflammatory factors, and metabolites in Beas-2B. And the effect of Thy was blocked by T0070907, and rosiglitazone promoted the role of Thy. Thy may ameliorate intestinal dysbiosis and metabolic disorders via the lung-gut axis and regulate the levels of PPAR-γ to mitigate LPS-induced ALI.

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