Intestinal Flora Disorder by Smoking Aggravation Inflammatory Reaction of Sepsis Through Regulation of the Mitochondrial Damage Through NLRP3 Inflammasome by FFAR2

Background: Sepsis is a common critical illness in ICU and always a great difficulty in clinical treatment, is associated with intestinal flora disorder. However, the biological contribution of chronic smoking on intestinal flora disorder of sepsis has not been previously investigated. We investigated the mechanisms by which intestinal flora disorder by smoking, a possible role for distinguish sepsis, contributes to the pathogenesis of sepsis-induced inflammatory reaction. Methods: We performed studies with mice were induced to sepsis by Cecal ligation and puncture (CLP), CLP mice were raised with intestinal flora disorder (OM, orally microbiome) by smoking. Lung tissues and cell samples were analyzed by histology, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. Findings: Smoking significantly brought about intestinal flora disorder in sepsis model. Intestinal flora disorder by smoking promoted the risk of sepsis-induced inflammatory reactions. Intestinal flora disorder by smoking reduced short chain fatty acid (SCFAs) to open ROS-dependently mitochondrial damage in macrophage of sepsis model via the activation of NLRP3 Inflammasome by FFAR2/STAT3/ EBP50/Nox1/p47phox signal channel. Interpretation: These findings identify smoking-induced intestinal flora disorder as a possible important pathogenic factors of sepsis and may shed lights on understanding how sepsis-induced inflammation reaction. Funding: This work was supported by National Natural Science Foundation of China (81173134); Focus on research and development planning projects of Anhui Science and Technology Department (1804h080242); Natural science research project of Anhui university (KJ2017A248); Talent Introduction Program of Yijishan Hospital of Wannan Medical College (YR202005), Science and Technology Innovation Team of Yijishan Hospital of Wannan Medical College (YPF2019016) and Key project research fund of Wannan Medical College (WK2020ZF03 and WK2020F23). Declaration of Interest: The authors declare no competing interests. Ethical Approval: All animal experiments were approved by the Animal Care and Use Committee of Yijishan Hospital of Wannan Medical College.