4.7 Article

PM2.5 induced weight loss of mice through altering the intestinal microenvironment: Mucus barrier, gut microbiota, and metabolic profiling

期刊

JOURNAL OF HAZARDOUS MATERIALS
卷 431, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.jhazmat.2022.128653

关键词

PM2.5; Weight loss; Intestinal microenvironment; Gut microbiome; Ileum metabolomics

资金

  1. National Natural Science Foundation of China [42007370]
  2. China Postdoctoral Science Foundation [2020M670054ZX]
  3. Post-doctoral Foundation of West China Hospital [2020HXBH146]

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Exposure to PM2.5 was found to cause weight loss in mice and disrupt gut microbiota, ileum metabolism, and liver and ileum histopathology. Specific changes were observed in the richness and function of fecal flora, as well as in the levels of key metabolites in the ileum. Analysis revealed that suppression of certain metabolic pathways and stimulation of ABC transporters might contribute to liver injury, ileum inflammation, and weight loss in mice.
The experimental evidences linking PM2.5 exposure to weight status disorder and the associated mechanisms were lacked. Here, we demonstrated exposure of 198.52 mu g/m(3) PM2.5 (Baoji city, China) for 40 days induced body weight loss of male Balb/C mice, and then increased after 14-day recovery. Correspondingly, gut micro biota dysbiosis, ileum metabolism alterations, and histopathological changes of liver and ileum elucidated the underlying mechanism. The richness and function modules of flora in feces significantly reduced after exposure, and the ratios of Bacteroidetes/Firmicutes reduced from 1.58 to 0.79. At genus level, Lactobacillus and Clostridium increased markedly, while Bacteroides and Parabacteroides decreased at day 40. After recovery, Oscillospira became the dominant genus. Additionally, the key metabolites in the ileum mediated by PM2.5 identified by metabolomics included arachidonic acid, prostaglandin H-2, prostaglandin F2 alpha, 5(S)-HPETE, AMP, and deoxyadenosine. Accordingly, conjoint analysis between the gut micorbiota and metabolic profiling revealed suppression of Arachidonic acid metabolism, linoleic acid metabolism, and PPAR signaling pathway and stimulation of ABC transporters might contribute to the liver injury, ileum inflammation, and then weight loss of mice. Our findings suggested PM2.5 affected weight status of mice by meditating intestinal microenvironment, and provided new insight for further diagnosis of the air pollution dependent disease.

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