연구성과 홍보

Exp Mol Med. 2023 Oct;55(10):2260-2268.

Title : Systemic antibiotics cause deterioration of emphysema associated with exaggerated inflammation and autophagy

Authors : Na Hyun Kim1, Bo-Yun Choi2, Eun Sil Kim3, Su Jung Kim4, Jeong Yeon Hong4, Sun-Hee Heo1, Jin-Yong Jeong3, Kyunggon Kim4, Hyun Ju Yoo3, Woo Jun Sul2, Sei Won Lee5*

Affiliations :

1Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

2Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi-do, Republic of Korea.

3Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center and Department of Microbiology, University of Ulsan College of Medicine, Seoul, Republic of Korea.

4Department of Convergence Medicine, Asan Medical Center, Department of Digital Medicine, University of Ulsan, College of Medicine, Seoul, Republic of Korea.

5Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

DOI: 10.1038/s12276-023-01099-6.

Abstract :

The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.