The pathophysiology of vaginally inserted polypropylene midurethral mesh tape complications, based on the microbiome and biofilms

Abstract

Background: Stress urinary incontinence commonly affects women, and effective treatment is vital. Midurethral mesh slings provided women with effective treatment; however long-term complications of chronic pain, vaginal mesh exposure and lower urinary tract perforation have come to light. Surgery to excise mesh may not adequately manage all complications. The pathophysiology of complications is not well understood, but felt to be related to a heightened inflammatory response to mesh implants. It is possible for the local microbiome to result in heightened inflammation. Midurethral mesh slings are inserted sterile, but may be exposed to the host’s local microbiome at the time of implantation. Aim: the overall aim of this thesis is to identify the mesh microbiome, correlate this with different complications; and identify the persistence of bacteria on midurethral slings as biofilms. Methods: Literature review as undertaken to understand what is known about the development of vaginally implanted mesh complications. Women who had undergone transobturator midurthreal mesh sling excision were followed up to assess for resolution of complications. Women undergoing midurethral mesh sling excision were invited to participate in a study of biofilms and the microbiome. Imaging Methodology was developed and validated for visualisation of biofilms on midurethral mesh slings using confocal laser scanning microscopy. Biofilm volumes were compared by site and complication groups. Samples of explanted midurethral mesh slings, urine, skin and vaginal swabs underwent DNA extraction, PCR amplification of the v4 16S RNA region and next generation sequencing to generate microbiome libraries which were analysed. Results: Women undergoing mesh excision may not experience improvement in their symptoms, may develop new stress incontinence but are overall satisfied with mesh excision surgery. Bacterial biofilms persist on midurethral mesh sling, regardless of complication and use of long-term antibiotics. The microbiome of midurethral mesh slings most closely resembles the urinary microbiome. Differing microbial communities appear to be associated with different complications: vaginal mesh exposure is associated with a different vaginal microbiome; lower urinary tract perforation of mesh is associated with a different urinary microbiome; pain sites are associated with a different skin microbiome. Conclusions: Data presented in this thesis highlights the need for understanding the role of different bacteria in promoting differing host responses. Future work may target a “hostile microbiome” as mesh complication treatment, or alter such a microbiome prior to implantation.

Date of Award	9 Feb 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Andrew Mcbain (Supervisor) & Fiona Reid (Supervisor)