Tian Xiaoli, Hellman Judith, Horswill Alexander R., Crosby Heidi A., Francis Kevin P., Prakash Arun
Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, United States.
Department of Immunology and Microbiology, Anschutz Medical Campus, University of Colorado, Aurora, CO, United States
Front Microbiol. 2019 Feb 14;10:159. doi: 10.3389/fmicb.2019.00159. eCollection 2019.
Short-chain fatty acids (SCFA) are important dietary and microbiome metabolites that can have roles in gut immunity as well as further afield. We previously observed that gut microbiome alteration via antibiotics led to attenuated lung inflammatory responses. The rationale for this study was to identify gut microbiome factors that regulate lung immune homeostasis. We first investigated key factors within mouse colonic lumen filtrates (CLF) which could elicit direct inflammatory effects . We identified lipopolysaccharide (LPS) and SCFAs as key CLF ingredients whose levels and inflammatory capacity changed after antibiotic exposure in mice. Specifically, the SCFA propionate appeared to be a key regulator of LPS responses . Elevated propionate: acetate ratios, as seen in CLF after antibiotic exposure, strongly blunted inflammatory responses . , exposure of lungs to high dose propionate, to mimic how prior antibiotic exposure changed SCFA levels, resulted in diminished immune containment of pneumonia. Finally, we discovered an enrichment of propionate-producing gut bacteria in mice with reduced lung inflammation following lung ischemia reperfusion injury . Overall, our data show that propionate levels can distinctly modulate lung immune responses and and that gut microbiome increased production of propionate is associated with reduced lung inflammation.
短链脂肪酸（SCFA）是重要的饮食和微生物群代谢产物，在肠道免疫以及其他方面发挥作用。我们之前观察到，抗生素导致的肠道微生物群改变会减弱肺部炎症反应。本研究的目的是确定调节肺部免疫稳态的肠道微生物群因素。我们首先研究了小鼠结肠腔滤液（CLF）中可能引发直接炎症效应的关键因素。我们确定脂多糖（LPS）和短链脂肪酸是CLF的关键成分，其水平和炎症能力在小鼠接受抗生素暴露后发生了变化。具体而言，丙酸似乎是LPS反应的关键调节因子。抗生素暴露后CLF中出现的丙酸与乙酸比例升高，强烈减弱了炎症反应。将肺部暴露于高剂量丙酸中，以模拟先前抗生素暴露如何改变短链脂肪酸水平，导致对肺炎的免疫控制减弱。最后，我们发现肺缺血再灌注损伤后肺部炎症减轻的小鼠中，产生丙酸的肠道细菌有所富集。总体而言，我们的数据表明，丙酸水平可显著调节肺部免疫反应，并且肠道微生物群中丙酸产量增加与肺部炎症减轻有关。
