Intestinal Microbiota-derived Propionic Acid Protects against Zinc Oxide Nanoparticle-induced Lung Injury

作者全名："Zhang, Yandan; Zhang, Lingbing; Mao, Lejiao; Fan, Jingchuan; Jiang, Xuejun; Li, Na; Fan, Yinzhen; Jiang, Ziqi; Qin, Xia; Qiu, Feng; Jiang, Yu; Liu, Gang; Zhang, Jun; Chen, Chengzhi; Zou, Zhen"

作者地址："[Zhang, Yandan; Mao, Lejiao; Fan, Jingchuan; Li, Na; Fan, Yinzhen; Jiang, Ziqi; Zhang, Jun; Zou, Zhen] Chongqing Med Univ, Mol Biol Lab Resp Dis, Inst Life Sci, Chongqing, Peoples R China; [Jiang, Xuejun] Chongqing Med Univ, Ctr Expt Teaching Publ Hlth, Expt Teaching & Management Ctr, Chongqing, Peoples R China; [Jiang, Xuejun; Zhang, Jun; Zou, Zhen] Chongqing Med Univ, Res Ctr Environm & Human Hlth, Chongqing, Peoples R China; [Chen, Chengzhi] Chongqing Med Univ, Sch Publ Hlth & Management, Dept Occupat & Environm Hlth, Chongqing, Peoples R China; [Zhang, Lingbing; Qin, Xia; Qiu, Feng] Chongqing Med Univ, Dept Pharm, Affiliated Hosp 1, Chongqing, Peoples R China; [Jiang, Yu] Chongqing Med Univ, Univ Town Hosp, Dept Resp Med, Chongqing, Peoples R China; [Liu, Gang] Chongqing Med Univ, Dept Emergency, Univ Town Hosp, Chongqing, Peoples R China"

通信作者："Zou, Z (通讯作者)，Chongqing Med Univ, Mol Biol Lab Resp Dis, Inst Life Sci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000891796900012

JCR分区：Q1

影响因子：6.4

年份：2022

卷号：67

期号：6

开始页：680

结束页：694

文献类型：Article

关键词：acute lung injury; zinc oxide nanoparticles; intestinal microbiota; propionic acid; macrophages

摘要："With the rapid development of nanotechnology, the risks of accidental and/or occupational exposure to zinc oxide nanoparticles (ZnONPs) are increasing. Inhalation of ZnONPs induces metal fume fever in humans and acute lung injury (ALI) in animal models. Although the intestinal microbiota is considered an important modulator of various diseases, the role and mechanism of intestinal microbiota in the pathology of ZnONP-induced ALI are unclear. Herein, we established an intratracheal instillation of a ZnONP-induced ALI mouse model and found that the inhalation of ZnONPs caused ALI along with a perturbation of intestinal flora. Antibiotic cocktail treatment-mediated depletion of intestinal microbiota aggravated ZnONP-induced ALI, and in contrast, fecal microbiota transplantation-mediated restoration of intestinal microbiota exerted the opposite effects. A decrease in short-chain fatty acids, the intestinal microbiota-derived metabolites in the plasma-in particular, acetic acid and propionic acid-occurred after exposure to ZnONPs. It is important to note that supplementation with propionic acid, but not acetic acid, ameliorated ZnONP-induced ALI. We also showed that the source of inflammatory cytokines might partially be the infiltration of macrophages. Supplementation with propionic acid was found to act on macrophages through the receptor GPR43, because knockdown of GPR43 sharply reversed the protective effects of propionic acid during the ZnONP-induced inflammatory response and oxidative stress in both primary alveolar macrophages and RAW 264.7 macrophage cell lines. Altogether, a novel gut-lung axis mechanism is revealed in which intestinal microbiota and their derived metabolite propionic acid play protective roles against ZnONP-induced ALI and suggest that fecal microbiota transplantation and supplementation with propionic acid are potential remedy strategies."

基金机构："Chongqing Talents: Exceptional Young Talents Project [CQYC2020058650]; National Natural Science Foundation of China [81903358]; Natural Science Foundation of Chongqing [cstc2021ycjh-bgzxm0105, cstc2020jcyj-msxmX0155, cstc2021jcyjmsxmX0141]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJCXZD2020020, KYYJ202005]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0038]; Chongqing Bayu Young Scholar Program"

基金资助正文："Supported by Chongqing Talents: Exceptional Young Talents Project (CQYC2020058650), the National Natural Science Foundation of China (81903358), the Natural Science Foundation of Chongqing (cstc2021ycjh-bgzxm0105, cstc2020jcyj-msxmX0155, and cstc2021jcyjmsxmX0141), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJCXZD2020020 and KYYJ202005), and the Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0038). Z.Z., C.C., and J.Z. received grants from the Chongqing Bayu Young Scholar Program."