Effect of Shuangshen Pingfei Formula on Gut Microbiota in BLM-Induced Pulmonary Fibrosis Rats

  OBJECTIVE  To explore the effect of Shuangshen Pingfei formula (SSPF) on gut microbiota in bleomycin (BLM)-induced pulmonary fibrosis rats.

  METHODS  The PF rat model was established by intratracheal instillation of BLM. The rats were randomly divided into three groups (n=6-8): saline group, BLM+saline group, BLM+SSPF group. SSPF (6.5 g·kg^-1) was given every day via gavage starting after 1 days of BLM/normal saline instillation. Equal volumes of saline were given to rats in the other two groups. At 28 days post-treatment, rat lungs were harvested to detect the lung coefficient and the status of lung inflammation and fibrosis, and hydroxyproline (HYP) content and metalloprotein 7 (MMP7) mRNA expression were measured. 16S rDNA sequencing technology was applied to detect intestinal microflora changes. The microbiota related to SSPF-induced improvement of fibrosis was screened out by correlation analysis. The possibility of gut microbiota in identifying pulmonary fibrosis and SSPF-induced anti-pulmonary fibrosis activity was assessed by ROC analysis.

  RESULTS  Histological analysis showed that chronic inflammation and pulmonary fibrosis occurred 28 days after BLM instillation, and decreased after SSPF administration. BLM increased HYP content and MMP7 mRNA expression, which were reversed by SSPF treatment. 17 genera of microflora were altered in the model, which were improved after administration of SSPF. Combined with correlation analysis, SSPF decreased the abundance of some pathogenic bacteria such as Fusobacterium, Shigella, Allobaculum and Clostridium, and increased the abundance of some beneficial bacteria such as Aggregatibacter, Collinsella, Bifidobacterium and Lactobacillus. ROC analysis indicated that it was dependable to identify pulmonary fibrosis and verify SSPF-induced improvement in pulmonary fibrosis by using gut microorganisms.

  CONCLUSION  Pulmonary fibrosis can cause the changes in gut microbiota, and SSPF can improve this disorder by up-regulating probiotics and down-regulating the abundance of pathogenic bacteria.