Hesperetin Mitigate Idiopathic Pulmonary Fibrosis by Regulating Gut Microbiota and Acetate and Butyrate Levels via the Gut‐Lung Axis

In the post‐epidemic and aging era, idiopathic pulmonary fibrosis (IPF) has become one of the major diseases endangering human health. Hesperetin, a prebiotic with multiple activities, aids in preventing lung diseases. Whether IPF effect gut microbiota and how the hesperetin inhibits IPF through the gut–lung axis remain unclear. This study evaluated the potential mechanism of different doses (100, 200 mg/kg/d) of hesperetin in inhibiting bleomycin‐induced IPF via the gut–lung axis. Results showed hesperetin significantly improved lung lesions including inflammatory cell infiltration, collagen deposition, pulmonary hypodynamism, and decreased antioxidant capacity. Furthermore, hesperetin balanced gut microbiota by increasing the abundance in Clostridia_UCG_014 and Lactobacillus and decreasing in Staphylococcus , accompanied by increased fecal short‐chain fatty acids (SCFAs) such as acetate and butyrate levels. Correlation analysis further suggests hesperetin may attenuate IPF via the gut–lung axis. Our research offers new evidence for hesperetin in preventing lung diseases as a key functional food component.