Lactobacillus paracasei L9 Ameliorates Pulmonary Fibrosis in Aged Mice via Gut‐Lung Axis‐Mediated Regulation of Immune Cell Migration

Age‐related pulmonary fibrosis (PF) imposes a growing global burden with limited therapies. This study explored the role of Lactobacillus paracasei L9 (L9) in alleviating PF in C57BL/6J mice and its mechanisms. Nine‐month oral administration of L9 (4 × 10 9 CFU/mL) suppressed collagen (Col‐) I deposition in aged mice, with no significant effect on Col‐III. Mechanistically, L9 inhibited the JNK‐HSF1 signaling pathway, thereby resulting in a 61% decrease in HSP47 expression, which is crucial for Col‐I synthesis. L9 reshaped the gut microbiota by increasing short‐chain fatty acid (SCFA)‐producing bacteria (e.g., Blautia), leading to a 97% increase in serum propionic acid and 193% increase in butyric acid; notably, the levels of SCFAs in the lungs were below the limit of detection. In L9‐treated mice, pulmonary IL‐17A levels and Th17 cell populations were reduced. In vitro, SCFAs directly inhibited Th17 cell differentiation and IL‐17A secretion, and IL‐17A was confirmed to promote Col‐I synthesis via the JNK‐HSF1 pathway in pulmonary fibroblasts. Consequently, L9 modulates the gut microbiota to produce SCFAs, which regulate naïve CD4 + T cell differentiation and migration via the gut‐lung axis. This reduces pulmonary Th17 cells and IL‐17A, thereby suppressing Col‐I synthesis in pulmonary fibroblasts and ultimately alleviating age‐related PF. In conclusion, this study highlights L9 as a microbiome‐targeted precision nutrition strategy for the adjuvant therapy of age‐related PF via the novel gut‐lung axis mechanism.