Pitt Norman, Morrissette Madeleine, Gates Michael F, Bargabos Rachel, Krumpoch Megan, Hawkins Bryson, Lewis Kim
Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, USA.
NPJ Biofilms Microbiomes. 2025 Mar 22;11(1):48. doi: 10.1038/s41522-025-00676-z.
Inflammation damages the epithelial cell barrier, allowing oxygen to leak into the lumen of the gut. Respiring E. coli and other Enterobacteriaceae produce proinflammatory lipopolysaccharide, exacerbating inflammatory bowel disease. Here we show that respiring membrane vesicles (MV) from E. coli ameliorate symptoms in a mouse model of gut inflammation. Membrane vesicle treatment diminished weight loss and limited shortening of the colon. Notably, oxygenation of the colonic epithelium was significantly decreased in animals receiving wild type MVs, but not MVs from an E. coli mutant lacking cytochromes. Metatranscriptomic analysis of the microbiome shows an increase in anaerobic Lactobacillaceae and a decrease in Enterobacteriaceae, as well as a general shift towards fermentation in MV-treated mice. This is accompanied by a decrease in proinflammatory TNF-α. We report that MVs may lead to the development of a novel type of a therapeutic for dysbiosis, and for treating IBD.
炎症会损害上皮细胞屏障，使氧气泄漏到肠腔中。进行呼吸作用的大肠杆菌和其他肠杆菌科细菌会产生促炎脂多糖，加剧炎症性肠病。在此，我们表明来自大肠杆菌的进行呼吸作用的膜泡（MV）可改善肠道炎症小鼠模型的症状。膜泡治疗减轻了体重减轻，并限制了结肠缩短。值得注意的是，接受野生型MV的动物结肠上皮的氧合作用显著降低，但来自缺乏细胞色素的大肠杆菌突变体的MV则没有这种情况。对微生物组的宏转录组分析表明，经MV处理的小鼠中厌氧乳酸菌科增加，肠杆菌科减少，并且总体上向发酵转变。这伴随着促炎细胞因子TNF-α的减少。我们报告说，MV可能会导致开发一种新型的治疗菌群失调和治疗炎症性肠病的疗法。
