Assessing the impact of triiodothyronine treatment on the lung microbiome of mice with pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF), an interstitial lung disease, is characterized by the exacerbation of progressive pulmonary fibrosis (PF). IPF primarily affects older individuals and can lead to respiratory failure. This study aimed to assess the effects of triiodothyronine (T₃) treatment on the lung microbiome of mice with PF.

Mice were perfused with bleomycin (BLM) to establish a PF model. Using a randomized design, 40 female specific pathogen-free (SPF) C57BL6/N mice were divided into four groups: saline, saline + T₃, BLM, and BLM + T₃. Histological morphology was assessed through Hematoxylin and Eosin staining as well as Masson’s Trichrome staining. For the identification of lung bacteria, 16S rRNA gene sequencing was employed. An Enzyme-Linked Immunosorbent Assay was used to measure total T₃ (TT₃), free T₃ (FT₃, and reverse T₃ (rT₃) levels in the peripheral serum.

T₃ treatment ameliorated BLM-induced lung fibrosis and structural damage. The microbiome experienced a decrease in the abundance of Proteobacteria, Bacteroides, and Actinomycetes and an increase in the abundance of Firmicutes when exposed to BLM; however, T₃ treatment reversed this effect. The four groups showed no significant difference in alpha microbiome diversity (P > 0.05). Serum concentrations of TT₃ and FT₃ were positively correlated with microbiome abundance (P < 0.05). Administration of T₃ enhanced the microbiota in PF without affecting the diversity and biological functions of the microbiome (P > 0.05).

The administration of T₃ demonstrated a favorable impact on the lung microbiota of mice afflicted with PF, thereby partially substantiating the potential role of T₃ as a therapeutic agent in the management of PF.