Microbiome Profile and Inflammatory Response in Women with Pelvic Organ Prolapse

Thursday, October 24, 2024

12:32 PM – 12:36 PM EDT

Location: Independence Ballroom E-H (Meeting Level 4)

Table 1. Patient Demographics

Figure 1. Alpha Diversity and LPS/LPS-BP Levels

Objectives: Gut dysbiosis has been associated with several inflammatory conditions, however there are no studies examining the gut microbiome in patients with pelvic organ prolapse (POP). We have previously shown evidence of inflammation in POP histologically and with the presence of elevated bacterial lipopolysaccharide (LPS) and host LPS-binding protein (LPS-BP). Circulating LPS can be traced to deleterious gut microbiota and thus is referred to as arising from “leaky gut” or more formally, metabolic endotoxemia (ME), which has been associated with chronic low-grade tissue inflammation, metabolic syndrome, and damaging connective tissue and cartilage. We aim to identify systemic inflammation and characterize the gut microbiome in POP compared to controls.

Methods: This is a prospective cohort study of women undergoing surgery for apical POP at the University of Colorado from February 2023-February 2024. Stool specimens and blood collections were collected preoperatively. Uterosacral ligament (USL) samples were obtained at the time of surgery and stored at -80C until the time of processing.

Histologic analyses were performed on the USL to classify the phenotype using the POP-HQ system. ELISA assays were performed on plasma samples to evaluate levels of LPS and LPS-BP. Stool bacterial DNA was then extracted and rRNA PCR products were quantified, pooled, and sequenced at the Genomics and Microarray core at the University of Colorado, Anschutz Medical Campus. Dada2 was used to bin identical sequences, defining Amplicon Sequence Variants. Bacterial alpha and beta diversity were compared between POP and controls. Mann-Whitney U was used to compare the relative abundance of LPS and LPS-BP.

Results: Ninety-three patients were recruited with 7 excluded due to antibiotic usage. To account for differences in age, analyses were performed on 52 patients  55 years old (30 POP and 22 control). Demographic data was not different between groups apart from higher vaginal parity in POP (Table 1).

While various analyses suggested an overall positive correlation between alpha diversity and POP stage, this trend did not reach statistical significance (Figure 1). Beta diversity was not different between groups. Despite no disparity in serum LPS, serum LPS-BP was significantly higher in POP compared to controls (Figure 1).

Conclusions: Our findings demonstrated a significant increase in LPS-BP levels in individuals with POP compared to control subjects, despite comparable overall microbiome profiles. LPS-BP, an acute phase protein induced by circulating LPS, serves as a more stable biomarker reflecting the host’s inflammatory response to gut microbiota-derived antigens. Our findings suggest dysbiosis is not causing permeability of the bowel and that other alternative mechanisms such as weak connective tissue in the bowel lining may be driving systemic elevations of LPS-BP. Our small prospective study lays the groundwork for the development of noninvasive screening methods to identify potentially modifiable risk factors and individuals susceptible to POP.

Disclosure(s):

Ashley E. Hilton, MD: No financial relationships to disclose

Dylan M. Asmar: No financial relationships to disclose

Lina M. Loza, MD: No financial relationships to disclose

Joshua Johnson, Ph.D.: No financial relationships to disclose

David J. Orlicky, PhD: No financial relationships to disclose

Jaime Arruda, MD: No relevant disclosure to display

Lauren Rascoff, MD: No financial relationships to disclose

Juana Hutchinson-Colas, MD, MBA,: No financial relationships to disclose

Marsha K. Guess, MD, MS: No financial relationships to disclose

Kathleen A. Connell, MD: No financial relationships to disclose

Presenting Author(s)

Ashley E. Hilton, MD (she/her/hers)

Fellow Physician
University of Colorado
Aurora, Colorado, United States

Disclosure(s): No financial relationships to disclose

Co-Author(s)

DA

Dylan M. Asmar (he/him/his)

Ph.D. Candidate
Stanford Intelligent Systems Laboratory
Stanford, California, United States

Disclosure(s): No financial relationships to disclose
LL

Lina M. Loza, MD (she/her/hers)

Urogynecology Fellow
University of Colorado
Denver, Colorado, United States

Disclosure(s): No financial relationships to disclose
JJ

Joshua Johnson, Ph.D.

Associate Professor
University of Colorado-Denver
Aurora, Colorado, United States

Disclosure(s): No financial relationships to disclose
DO

David J. Orlicky, PhD (he/him/his)

Associate Professor of Pathology
University of Colorado Anschutz Medical Center
DenverAurora, Colorado, United States

Disclosure(s): No financial relationships to disclose
JA

Jaime Arruda, MD

Professor
University of Colorado
Denver, Colorado, United States

Disclosure(s): No relevant disclosure to display
LR

Lauren Rascoff, MD

Assistant Professor
University of Colorado
Aurora, Colorado, United States

Disclosure(s): No financial relationships to disclose
JH

Juana Hutchinson-Colas, MD, MBA, (she/her/hers)

Professor of Obstetrics and Gynecology
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States

Disclosure(s): No financial relationships to disclose
Marsha K. Guess, MD, MS

Associate Professor
The University of Colorado School of Med
Aurora, Colorado, United States

Disclosure(s): No financial relationships to disclose
Kathleen A. Connell, MD (she/her/hers)

Professor, Division Chief
University of Colorado School of Medicine/Anschutz Medical Center
Aurora, Colorado, United States

Disclosure(s): No financial relationships to disclose