Chronic exposure to ambient particulate matter induces gut microbial dysbiosis in a rat COPD model

Naijian Li, Zhaowei Yang, Baoling Liao, Tianhui Pan, Jinding Pu, Binwei Hao, Zhenli Fu, Weitao Cao, Yuming Zhou, Fang He, Bing Li, Pixin Ran, Naijian Li, Zhaowei Yang, Baoling Liao, Tianhui Pan, Jinding Pu, Binwei Hao, Zhenli Fu, Weitao Cao, Yuming Zhou, Fang He, Bing Li, Pixin Ran

Abstract

Background: The role of the microbiota in the pathogenesis of chronic obstructive pulmonary disease (COPD) following exposure to ambient particulate matter (PM) is largely unknown.

Methods: Fifty-four male Sprague-Dawley rats were exposed to clean air, biomass fuel (BMF), or motor vehicle exhaust (MVE) for 4, 12, and 24 weeks. We performed pulmonary inflammation evaluation, morphometric measurements, and lung function analysis in rat lung at three different times points during exposure. Lung and gut microbial composition was assessed by 16S rRNA pyrosequencing. Serum lipopolysaccharide levels were measured and short-chain fatty acids in colon contents were quantified.

Results: After a 24-week PM exposure, rats exhibited pulmonary inflammation and pathological changes characteristic of COPD. The control and PM exposure (BMF and MVE) groups showed similar microbial diversity and composition in rat lung. However, the gut microbiota after 24 weeks PM exposure was characterized by decreased microbial richness and diversity, distinct overall microbial composition, lower levels of short-chain fatty acids, and higher serum lipopolysaccharide.

Conclusion: Chronic exposure to ambient particulate matter induces gut microbial dysbiosis and metabolite shifts in a rat model of chronic obstructive pulmonary disease.

Keywords: Biomass fuel; COPD; Gut microbiome; Motor vehicle exhaust.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic overview of the study workflow. a A total of 54 rats were randomly divided into three groups (control [CON], biomass fuel [BMF], and motor vehicle exhaust [MVE]; n = 6 per group) and exposed for 4, 12, or 24 weeks. Lung tissue was assessed histologically and gut microbial composition was assessed by 16S rRNA pyrosequencing. Serum lipopolysaccharide (LPS) levels were measured and short-chain fatty acids (SCFAs) in colon contents were quantified. b Particulate matter (PM) concentrations and particle size distributions during exposure. Rats exposed to biomass fuel (BMF) inhaled higher concentrations of PM with a diameter ≤ 10, 2.5, and 1 μm (PM10, PM2.5, and PM1) than rats exposed to motor vehicle exhaust (MVE). Boxes and the inside line represent the mean ± SD for PM2.5
Fig. 2
Fig. 2
Exposure to biomass fuel (BMF) and motor vehicle exhaust (MVE) induces pulmonary inflammation in rats. a Effects of BMF and MVE exposure on body weight. b Particle sediments were observed in bronchoalveolar lavage fluid in the BMF and MVE groups during the exposure period (n = 6). c The levels of total protein in BALF. d BALF total leukocyte counts. e, f BALF alveolar macrophages counts and neutrophil counts. n = 6; *p < 0.05, **p < 0.01. CON, control group
Fig. 3
Fig. 3
Exposure to biomass fuel (BMF) and motor vehicle exhaust (MVE) induces effects consistent with chronic obstructive pulmonary disease in rats. a Lung sections show significant increases in the mean linear intercept after 24 weeks of BMF and MVE exposure. b The thickness of the small airway wall increased significantly in the rats after 24 weeks of BMF and MVE exposure. c Effects of BMF and MVE exposure on rat pulmonary function test results. n = 6. **p < 0.01. CON, control group
Fig. 4
Fig. 4
Gut microbial abundance and diversity following exposure to biomass fuel or motor vehicle exhaust. Comparison of the operational taxonomic units (OTUs) (a) and alpha diversity (as assessed by the Chao 1 (b) and PD_whole_tree (c) indices; n = 6 per group). CON, control group; BMF, biomass fuel exposure group; MVE, motor vehicle exhaust exposure group
Fig. 5
Fig. 5
Relative proportions of major bacterial phyla following exposure to particulate matter. Microbial abundance was measured in colon contents from rats exposed to clean air (CON) and to particulate matter from biomass fuel (BMF) or motor vehicle exhaust (MVE)
Fig. 6
Fig. 6
Effect of particulate matter exposure on community diversity and richness of the lung microbiota. Operational taxonomic units (OTUs) (a) and microbial diversity (Shannon index (b) and Chao 1 index (c)). Composition and relative abundances of bacterial phyla in different groups after 4, 12 and 24 weeks exposure (d-f). Results are expressed as mean ± SD; n = 6 rat. CON, control group; BMF, biomass fuel exposure group; MVE, motor vehicle exhaust exposure group
Fig. 7
Fig. 7
Microbial metabolites in colon contents of controls (CON) and rats exposed to biomass fuel (BMF) or motor vehicle exhaust (MVE). a Levels of total short-chain fatty acids (SCFAs) were lower in the MVE groups after 24 weeks of exposure. b Levels of acetic acid were lower in the MVE groups, especially after 24 weeks of exposure. c, d Levels of propionic acid and caproic acid did not differ between groups. e Serum lipopolysaccharide (LPS) levels in the three groups after 4 and 24 weeks of exposure. f Elevated serum LPS levels were correlated with the mean linear intercept. Boxes and the inside line represent the mean ± SD; each dot corresponds to a sample. n = 6. *p < 0.05, **p < 0.01

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