Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, United States of America.
Global Scientific Affairs and Nutrition Policy, Research and Development, Ocean Spray Cranberries, Inc., Lakeville-Middleboro, Massachusetts, United States of America.
PLoS One. 2019 Nov 12;14(11):e0224836. doi: 10.1371/journal.pone.0224836. eCollection 2019.
The opportunistic pathogen Escherichia coli, a common member of the human gut microbiota belonging to the Enterobacteriaceae family, is the causative agent of the majority of urinary tract infections (UTIs). The gut microbiota serves as a reservoir for uropathogenic E. coli where they are shed in feces, colonize the periurethral area, and infect the urinary tract. Currently, front line treatment for UTIs consists of oral antibiotics, but the rise of antibiotic resistance is leading to higher rates of recurrence, and antibiotics cause collateral damage to other members of the gut microbiota. It is commonly believed that incorporation of the American cranberry, Vaccinium macrocarpon, into the diet is useful for reducing recurrence of UTIs. We hypothesized such a benefit might be explained by a prebiotic or antimicrobial effect on the gut microbiota. As such, we tested cranberry extracts and whole cranberry powder on a human gut microbiome-derived community in a gut simulator and found that cranberry components broadly modulate the microbiota by reducing the abundance of Enterobacteriaceae and increasing the abundance of Bacteroidaceae. To identify the specific compounds responsible for this, we tested a panel of compounds isolated from cranberries for activity against E. coli, and found that salicylate exhibited antimicrobial activity against both laboratory E. coli and human UTI E. coli isolates. In a gut simulator, salicylate reduced levels of Enterobacteriaceae and elevated Bacteroidaceae in a dose dependent manner.
机会性病原体大肠杆菌是肠杆菌科家族中人类肠道微生物群的常见成员,也是大多数尿路感染(UTI)的病原体。肠道微生物群是尿路致病性大肠杆菌的储库,它们会随粪便排出,定植于尿道周围区域,并感染泌尿道。目前,UTI 的一线治疗方法是口服抗生素,但抗生素耐药性的上升导致复发率更高,而且抗生素会对肠道微生物群的其他成员造成附带损害。人们普遍认为,将美洲蔓越莓(Vaccinium macrocarpon)纳入饮食有助于减少 UTI 的复发。我们假设这种益处可能是由于对肠道微生物群的益生元或抗菌作用。因此,我们在肠道模拟器中对源自人类肠道微生物组的群落测试了蔓越莓提取物和全蔓越莓粉,发现蔓越莓成分通过减少肠杆菌科的丰度和增加拟杆菌科的丰度来广泛调节微生物群。为了确定负责这种情况的特定化合物,我们测试了一组从蔓越莓中分离的化合物对大肠杆菌的活性,发现水杨酸对实验室大肠杆菌和人类 UTI 大肠杆菌分离株均具有抗菌活性。在肠道模拟器中,水杨酸以剂量依赖的方式降低肠杆菌科的水平并升高拟杆菌科的水平。