Complex carbohydrates catabolism capacity of bladder microbiota inhabiting healthy and overactive female bladders

Overactive bladder syndrome (OAB) is a poorly understood symptom complex that affects 40% of females over the age of 40, with clinical features including urinary urgency and incontinence. In addition to inflammation, oxidative stress, nerve damage and reduced blood flow, alterations in the urinary microbiome (urobiome), specifically in bladder bacterial diversity, have been reported to be associated with OAB. Bladder bacteria are members of the urobiome along with viruses, archaea, fungi, and protozoans. The urobiome metabolism, particularly in relationship to host complex sugars (glycans), has been investigated recently in terms of glycosaminoglycan (GAG) utilization. Nevertheless, other urinary free oligosaccharides (FOS) have not yet been explored in both OAB and urobiome contexts. Similarly, a comprehensive search of microbial genes involved in host glycan metabolism in the bladder of adult females with or without OAB has not yet been reported. In this study, we investigated urinary FOS by mass spectrometry in women without OAB (asymptomatic controls), with OAB without incontinence (dry OAB), or with OAB with incontinence (wet OAB or urgency urinary incontinence, UUI). We also questioned the ability of commensal bladder bacteria to digest these FOS and other glycans, using bioinformatic tools to query publicly available bladder genomes isolated from affected and unaffected adult females to identify genes that encode polysaccharide lyases (PL) and glycoside hydrolases (GH). Our results show that FOS are present in a similar level in affected and unaffected controls with a few exceptions: ten FOS were found to differ between the OAB dry groups and either the control (four) or UUI (six) groups. Our results indicate that bladder microbiota from adult females both with and without OAB have the genetic capacity to digest host glycans and dietary sugars with subtle differences. Bladder bacteria isolated from females with OAB possess more GH/PL genes for host mucins, whereas bladder bacteria from controls possess more GH/PL genes for GAG digestion. In the control group, specifically, the genus Streptococcus possessed genes for the PL8 and GH88 enzymes, known to be involved in host GAG digestion. These novel bioinformatic data can enable future biochemical exploration of the urobiome's metabolism toward specific host glycans, such as GAGs, mucins O-glycans and N-glycans.