Neugent Michael L, Hulyalkar Neha V, Kumar Ashwani, Xing Chao, Zimmern Philippe E, Shulaev Vladimir, De Nisco Nicole J
bioRxiv. 2023 Jan 12:2023.01.11.523678. doi: 10.1101/2023.01.11.523678.
Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides composed of repeating disaccharide units of uronic acid and amino sugars. The luminal surface of the bladder epithelium is coated with a GAG layer. These urothelial GAGs are thought to provide a protective barrier and serve as a potential interaction site with the urinary microbiome (urobiome). Previous studies have profiled urinary GAG composition in mixed cohorts, but the urinary GAG composition in postmenopausal women remains undefined. To investigate the relationship between GAGs and recurrent UTI (rUTI), we profiled urinary GAGs in a controlled cohort of postmenopausal women. We found that chondroitin sulfate (CS) is the major urinary GAG in postmenopausal women and that urinary CS was elevated in women with active rUTI. We also associated urinary GAGs with urobiome composition and identified bacterial species that significantly associated with urinary GAG concentration. , and were positively associated with heparin sulfate or hyaluronic acid and bacterial species associated with vaginal dysbiosis were negatively correlated to urinary CS. Altogether, this work defines changes in urinary GAG composition associated with rUTI and identifies new associations between urinary GAGs and the urobiome that may play a role in rUTI pathobiology.
糖胺聚糖（GAGs）是由糖醛酸和氨基糖的重复二糖单元组成的线性带负电荷多糖。膀胱上皮的腔面覆盖有一层GAG层。这些尿路上皮GAGs被认为可提供保护屏障，并作为与泌尿微生物群（泌尿生物群）潜在的相互作用位点。以往研究已对混合队列中的尿GAG成分进行了分析，但绝经后女性的尿GAG成分仍不明确。为了研究GAGs与复发性尿路感染（rUTI）之间的关系，我们在一个绝经后女性对照队列中分析了尿GAGs。我们发现硫酸软骨素（CS）是绝经后女性主要的尿GAG，且活动性rUTI女性的尿CS升高。我们还将尿GAGs与泌尿生物群组成相关联，并鉴定出与尿GAG浓度显著相关的细菌种类。 ， 与硫酸肝素或透明质酸呈正相关，与阴道生态失调相关的细菌种类与尿CS呈负相关。总之，这项工作明确了与rUTI相关的尿GAG成分变化，并确定了尿GAGs与泌尿生物群之间可能在rUTI病理生物学中起作用的新关联。
