RF4 - Alterations to microbiome-derived Serum Metabolites in Colorectal Surgery Patients

Saturday, May 10, 2025

3:42 PM – 3:46 PM PT

Location: Ballroom 6B, Upper Level

Abstract Podium Presenter(s)

Jeffrey L. Roberson, MD

Resident
The Hospital of the University of Pennsylvania
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

Author(s)

CS

Clarissa Shoffler, B.S. chemistry

Research Specialist
University of Pennsylvania Metabolomics Core
Philadelphia, Pennsylvania, United States

Disclosure information not submitted.
Najjia N. Mahmoud, MD

Chief, Division of Colon and Rectal Surgery
University of Pennsylvania Health System
University of Pennsylvania
Philadelphia, PA, US

All of the relevant financial relationships listed below have been mitigated.
This individual has no relevant relationships with ineligible companies.
Joshua Bleier, MD, FACS, FASCRS (he/him/his)

Chairman of Surgery, Pennsylvania Hospital
University of Pennsylvania Health System
philadelphia, Pennsylvania, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no relevant relationships with ineligible companies.
Nicole M. Saur, MD (she/her/hers)

Associate Professor
University of Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
EP

Erica Pettke, MD, MPH, FACS (she/her/hers)

Assistant Professor of Surgery
University of Pennsylvania
philadelphia, PA, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no relevant relationships with ineligible companies.
PH

Paul Hernandez, MD

Assistant Professor
University of Pennsylvania
Philadelphia, Pennsylvania, United States

Disclosure information not submitted.
CP

Christopher Petucci, n/a

Metabolomics Core Director
Perelman School of Medicine
Philadelphia, Pennsylvania, United States

Disclosure information not submitted.

Senior Author(s)

LM

Lillias Maguire, MD (she/her/hers)

Assistant Professor of Surgery
University of Pennsylvania
Philadelphia, Pennsylvania, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no relevant relationships with ineligible companies.

Submitting Author(s)

LM

Lillias Maguire, MD (she/her/hers)

Assistant Professor of Surgery
University of Pennsylvania
Philadelphia, Pennsylvania, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no relevant relationships with ineligible companies.

All of the relevant financial relationships listed below have been mitigated.

Jeffrey L. Roberson, MD: This individual has no financial relationships with ineligible companies.

Najjia N. Mahmoud, MD: This individual has no relevant relationships with ineligible companies.

Joshua Bleier, MD, FACS, FASCRS: This individual has no relevant relationships with ineligible companies.

Nicole M. Saur, MD: This individual has no financial relationships with ineligible companies.

Erica Pettke, MD, MPH, FACS: This individual has no relevant relationships with ineligible companies.

Lillias Maguire, MD: This individual has no relevant relationships with ineligible companies.

Image or Table (Do Not add text here):

Purpose/Background: The serum metabolome is a real-time description of an individual’s biochemical activity. We sought to understand the metabolic changes of older patients undergoing the stress of colorectal surgery. Surgery provokes metabolic changes through multiple pathways including anesthesia, medications, alteration of diet, tissue damage, and, in the case of colorectal surgery in particular, profound alteration of the microbiome with antibiotic administration and bowel preparation.

Methods/Interventions: We identified 43 patients over 69 years of age undergoing elective abdominal colorectal operations. We collected plasma at three timepoints: preoperatively, post-operative day two, and between three and six weeks postoperatively. We performed untargeted LC/MS metabolomics using the Thermo UHPLC/Orbitrap ID-X mass spectrometer. Samples were first run by reversed-phase C18 chromatography and a separate sample was run by HILIC chromatography. Thermo Scientific’s Compound Discoverer was used to extract the metabolites from the raw data and identify metabolites through a curated database search. A Bonferroni correction was used to adjust p-values for multiple corrections.

Results/Outcomes: We identified 160 unique, annotated metabolites that were significantly different (Adj. p-value < 0.05) between the preoperative and POD2 metabolome, increased or decreased by at least 50% from preoperative levels, and were not components of the exposome. By 3–6-week postoperative follow-up, there were no significant differences from preoperative levels. Significantly different decreased metabolites on POD2 included the exclusively microbe-produced uremic toxins: p-Cresol sulfate, indoxyl proprionic acid, TMAO, and pseudouridine, which fell to < 20% of preoperative levels, likely reflecting peri-operative decreases in the bacterial taxa that exclusively produce these toxins. However, the bacterially-derived metabolite tyramine-O-sulfate rose by 15-45x compared to preoperative levels. Tyramine sulfate is generated by tyrosine decarboxylase expressing Enterococcus and has been implicated in Parkinson’s Disease related autonomic bowel dysfunction and colitis.

Conclusion/Discussion: We identified multiple significant changes to the metabolome in the perioperative period for older colorectal surgery patients. Striking among these changes are alterations in microbiome-derived serum metabolites that may reflect the different impact of antibiotics and bowel preparation individual bacterial species. Given the challenge of obtaining stool in this period, the serum metabolome may be an excellent window to studying the postoperative microbiome. Understanding these changes may be the first step in modifying the microbiome in the perioperative period to improve outcomes.