The Role Of Gut-lung Axis In Chronic Obstructive Pulmonary Disease And Its Mechanism

Background and aimsChronic obstructive pulmonary disease(COPD)is a worldwide public health concern.Although progress have been made in the treatment of symptoms and prevention of acute exacerbations,few advances have been achieved in ameliorating disease progression or affecting mortality.COPD is a complex disease with multiple sub-phenotypes that affects not only the lungs,but also the cardiovascular,gastrointestinal and immune systems,and its mechanisms are not completely understood.In recent years,the role of the microbiome,especially the intestinal microbiome,has attracted widespread attention.Some evidence suggests that imbalances in the intestinal flora can cause disease.In addition,through animal models and human fecal transplants,associations between the intestinal flora and the pathogenesis of various human diseases have been identified.However,little is known about the involvement of the gut microbiota in chronic obstructive pulmonary disease.Although COPD is primarily considered as a respiratory disease,it usually occurs concurrently with chronic gastrointestinal disease.Recent studies have linked changes in the composition and function of the intestinal microbes to the development of lung disease,but there are few studies on the intestinal-lung axis of chronic obstructive pulmonary disease.The characteristics of the gut microbiota in patients with chronic obstructive pulmonary disease remain to be determined,and the contribution of the gut microbiota to the progression of chronic obstructive pulmonary disease is unclear.【Objectives】The purpose of this study was to investigate whether changes in intestinal flora were associated with pulmonary inflammation and chronic obstructive pulmonary disease.【Research methods and results】Part 1: Analysis of intestinal flora in COPD patientsMethods We collected fecal specimens from 73 healthy people and 104 COPD patients(67 GOLDⅠ-Ⅱ,34 GOLD Ⅲ-Ⅳ)who met the inclusion criteria for 16 S r RNA sequencing and short-chain fatty acids(SCFAs)Concentration detection,analysis of intestinal flora characteristics and differences in metabolites by bioinformatics.Results 1.Compared with the healthy control group,COPD patients,especially those with COPD III-IV,showed a decrease in the abundance and diversity of intestinal flora.2.The composition of intestinal flora of patients with COPD was significantly different from that of the control group,and the Prevotella intestinal type was the main type.3.The concentration of short-chain fatty acids(SCFAs)in the intestinal flora metabolites in the stool of COPD patients decreased significantly.Part 2: The effect of intestinal flora imbalance on pulmonary inflammation in patients with COPDMethods Forty-five C57 BL / 6 mice were randomly divided into three groups.Three weeks after the oral administration of the combined antibiotics,the feces from healthy control patients(Health),COPDⅠ-Ⅱ and COPDⅢ-Ⅳ patients(3 times / week,total 4 weeks).16 S r RNA pyrosequencing to evaluate changes in intestinal flora,histological analysis to assess changes in lung tissue structure,flow cytometry to determine changes in T / B lymphocytes,cytokine kits to detect changes in serum cytokines,and Western blot detection to be slow Changes in levels of anti-lung protein.Results: 1.The intestinal flora abundance of C57 BL / 6 mice was significantly reduced after 3 weeks of combined application of antibiotics,and the intestinal flora abundance and diversity of the healthy control group and the COPD group significantly increased after inoculation.2.After transplantation of COPD donor stool to recipient mice,it was observed that the recipient mice’s body and lungs had increased inflammation,and the expression of airway mucus and airway remodeling-related proteins increased significantly.Part 3: The role of intestinal flora imbalance in the pathogenesis of COPDMethods Sixty C57 BL / 6 mice were randomly divided into four groups,and the stools from PBS,healthy control group,COPDⅠ-Ⅱ,and COPDⅢ-Ⅳ patients(2 times / week)were inoculated 3 weeks after the oral administration of combined antibiotics.)And simultaneous exposure to biofuels for 5 months(6h / day for 150 days).After the study was terminated,the lung function of the mice between the four groups was measured by a mouse lung function meter,the structural changes of the lung tissue were analyzed histologically,the T / B lymphocytes were measured by flow cytometry,and the serum inflammatory factors and protein immunity were detected by the cytokine kit.Blotting was used to detect the expression of proteins associated with COPD.Results: 1.After the combined fecal bacteria transplantation and biofuel exposure,mice transplanted with feces from COPD patients,especially those with COPD III-IV patients,showed worse lung function and more severe emphysema.change.2.The mucus secretion and airway remodeling of mice from stools of patients with COPD IIIIV were more significant.【Conclusion】1.COPD patients have intestinal flora disorders and reduced beneficial bacterial metabolites.2.COPD patients’ intestinal flora can induce COPD-like inflammation in the lungs of mice.3.The intestinal flora of COPD patients promoted the occurrence and development of COPD in a mouse model.4.Confirmed the role of "gut-lung axis" in the pathogenesis of COPD.