Effects of antibiotics and metals on lung and intestinal microbiome dysbiosis after sub-chronic lower-level exposure of air pollution in ageing rats

Vincent Laiman; Yu-Chun Lo; Hsin-Chang Chen; Tzu-Hsuen Yuan; Ta-Chih Hsiao; Jen-Kun Chen; Ching-Wen Chang; Ting-Chun Lin; Ssu-Ju Li; You-Yin Chen; Didik Setyo Heriyanto; Kian Fan Chung; Kai-Jen Chuang; Kin-Fai Ho; Jer-Hwa Chang; Hsiao-Chi Chuang

doi:10.1016/j.ecoenv.2022.114164

Effects of antibiotics and metals on lung and intestinal microbiome dysbiosis after sub-chronic lower-level exposure of air pollution in ageing rats

Ecotoxicol Environ Saf. 2022 Nov:246:114164. doi: 10.1016/j.ecoenv.2022.114164. Epub 2022 Oct 13.

Authors

Vincent Laiman¹, Yu-Chun Lo², Hsin-Chang Chen³, Tzu-Hsuen Yuan⁴, Ta-Chih Hsiao⁵, Jen-Kun Chen⁶, Ching-Wen Chang⁷, Ting-Chun Lin⁸, Ssu-Ju Li⁹, You-Yin Chen¹⁰, Didik Setyo Heriyanto¹¹, Kian Fan Chung¹², Kai-Jen Chuang¹³, Kin-Fai Ho¹⁴, Jer-Hwa Chang¹⁵, Hsiao-Chi Chuang¹⁶

Affiliations

¹ International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada - Dr. Sardjito Hospital, Yogyakarta, Indonesia. Electronic address: vincentharun29@gmail.com.
² Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: aricalo@tmu.edu.tw.
³ Department of Chemistry, College of Science, Tunghai University, Taichung, Taiwan. Electronic address: hsinchang@thu.edu.tw.
⁴ Department of Health and Welfare, College of City Management, University of Taipei, Taipei, Taiwan. Electronic address: thyuan@go.utaipei.edu.tw.
⁵ Graduate Institute of Environmental Engineering, National Taiwan University, Taipei, Taiwan. Electronic address: tchsiao@gmail.com.
⁶ Institute of Biomedical Engineering & Nanomedicine, National Health Research Institutes, Miaoli, Taiwan. Electronic address: jkchen@nhri.org.tw.
⁷ Industrial Ph.D. Program of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: love6xup@gmail.com.
⁸ Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: jimmy601521@gmail.com.
⁹ Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: louislee0722@gmail.com.
¹⁰ Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Industrial Ph.D. Program of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: irradiance@so-net.net.tw.
¹¹ Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada - Dr. Sardjito Hospital, Yogyakarta, Indonesia. Electronic address: didik_setyoheriyanto@mail.ugm.ac.id.
¹² National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: f.chung@imperial.ac.uk.
¹³ School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: kjc@tmu.edu.tw.
¹⁴ School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong. Electronic address: kfho@cuhk.edu.hk.
¹⁵ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Departments of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: m102094030@tmu.edu.tw.
¹⁶ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: chuanghc@tmu.edu.tw.

PMID: 36244167
DOI: 10.1016/j.ecoenv.2022.114164

Abstract

We investigated the effects of antibiotics, drugs, and metals on lung and intestinal microbiomes after sub-chronic exposure of low-level air pollution in ageing rats. Male 1.5-year-old Fischer 344 ageing rats were exposed to low-level traffic-related air pollution via whole-body exposure system for 3 months with/without high-efficiency particulate air (HEPA) filtration (gaseous vs. particulate matter with aerodynamic diameter of ≤2.5 µm (PM_2.5) pollution). Lung functions, antibiotics, drugs, and metals in lungs were examined and linked to lung and fecal microbiome analyses by high-throughput sequencing analysis of 16 s ribosomal (r)DNA. Rats were exposed to 8.7 μg/m³ PM_2.5, 10.1 ppb NO₂, 1.6 ppb SO₂, and 23.9 ppb O₃ in average during the study period. Air pollution exposure decreased forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory volume in 20 ms (FEV₂₀), and FEF at 25∼75% of FVC (FEF_25-75). Air pollution exposure increased antibiotics and drugs (benzotriazole, methamphetamine, methyl-1 H-benzotriazole, ketamine, ampicillin, ciprofloxacin, pentoxifylline, erythromycin, clarithromycin, ceftriaxone, penicillin G, and penicillin V) and altered metals (V, Cr, Cu, Zn, and Ba) levels in lungs. Fusobacteria and Verrucomicrobia at phylum level were increased in lung microbiome by air pollution, whereas increased alpha diversity, Bacteroidetes and Proteobacteria and decreased Firmicutes at phylum level were occurred in intestinal microbiome. Lung function decline was correlated with increasing antibiotics, drugs, and metals in lungs as well as lung and intestinal microbiome dysbiosis. The antibiotics, drugs, and Cr, Co, Ca, and Cu levels in lung were correlated with lung and intestinal microbiome dysbiosis. The lung microbiome was correlated with intestinal microbiome at several phylum and family levels after air pollution exposure. Our results revealed that antibiotics, drugs, and metals in the lung caused lung and intestinal microbiome dysbiosis in ageing rats exposed to air pollution, which may lead to lung function decline.

Keywords: Air pollution; Antibiotics; Lung function; Metals; Microbiome; PM(2.5).

MeSH terms

Aging
Air Pollutants* / analysis
Air Pollution* / analysis
Animals
Anti-Bacterial Agents / analysis
Dysbiosis / chemically induced
Environmental Exposure / analysis
Gastrointestinal Microbiome*
Lung
Male
Metals / analysis
Particulate Matter / analysis
Rats

Substances

Anti-Bacterial Agents
Particulate Matter
Metals
Air Pollutants