Interplay between gut homeostasis-regulating enzyme intestinal alkaline phosphatase and bacterial lipopolysaccharides in patients undergoing abdominal surgery for cancer

Li, Qiang (2025): Interplay between gut homeostasis-regulating enzyme intestinal alkaline phosphatase and bacterial lipopolysaccharides in patients undergoing abdominal surgery for cancer. Dissertation, LMU München: Medizinische Fakultät

Abstract

Background: Intestinal alkaline phosphatase (IAP) is a key player in preserving gut health, regulating bacterial populations, promoting gut barrier integrity, and dephosphorylating proinflammatory molecules like lipopolysaccharides (LPS). LPS, a virulence factor in gram-negative bacteria, triggers inflammatory responses. It is associated with various cancers (such as pancreatic, colorectal, and liver cancer) and negatively contributes to surgical outcomes (sepsis, postoperative cognitive function). IAP's potential in pancreatic, colorectal, and liver health is a reassuring aspect of our research, with current studies highlighting its critical interplay and potential therapeutic implications across diverse health conditions. Study Design: The study encompassed 118 patients from the Department of General, Visceral and Transplant Surgery at Ludwig-Maximilians-University between June 22nd, 2022, and September 15th, 2023. Among them, 91 had cancer (25 pancreatic, 21 colorectal, 14 liver, 31 other adenocarcinomas), and 27 had non-cancer cases. Additionally, 8 blood samples from healthy individuals served as controls. We conducted the Para-Nitrophenyl Phosphate (PNPP) method to assess the stool IAP activity of 23 preoperative samples. Additionally, we utilized the Limulus Amebocyte Lysate (LAL) assay to measure serum LPS levels of 113 preoperative and 35 postoperative samples and the Human IAP ELISA assay to quantify serum IAP concentrations of 83 preoperative samples. Results: Our study revealed a significant negative correlation between preoperative stool IAP and preoperative serum LPS (r=-0.514, p=0.029), reinforcing previous findings in pancreatic cancer patients and the entire study population. Moreover, a positive correlation between preoperative stool and serum IAP emerged (r=0.524, p=0.040), while preoperative serum IAP displayed a negative correlation with serum LPS (r=-0.397, p<0.001). The analysis of preoperative serum IAP and LPS alongside various clinical parameters showed that preoperative serum IAP values displayed a negative association with preoperative IL-6 levels (r=-0.334, p=0.020) and CRP (r=-0.348, p=0.001), as well as a positive relationship with albumin (r=0.425, p<0.001). Preoperative serum IAP levels were notably lower in the cancer group compared to healthy controls (p=0.0012). Preoperative serum IAP levels were lower in patients diagnosed with pancreatic (p=0.0144) and colorectal cancer (CRC) (p = 0.0349). However, no significant differences in preoperative serum IAP were detected when comparing liver cancer and healthy controls (p=0.0984). In all abdominal surgery patients (p=0.0071) and all cancer resected patients (p=0.0128), respectively, a significant reduction in postoperative serum LPS levels compared to preoperative levels was observed, indicating a potential impact of surgeries on LPS levels. We showed that higher preoperative serum IAP levels were associated with a favorable outcome (Clavien-Dindo ≤ II) following abdominal surgery (p = 0.0016). A ROC analysis identified a cutoff value for preoperative serum IAP that could predict surgical outcomes effectively (AUC = 0.749; Youden-Index = 0.4620). Higher preoperative serum IAP levels correlated with better abdominal surgical outcomes, also indicated by shorter intensive care unit (ICU) stays (r = -0.375, p = 0.012). Among patients undergoing surgery for all cancer resection, preoperative serum IAP values were lower in the Clavien-Dindo > II, in which III or higher is relevant to complications where intervention is required, compared to the Clavien-Dindo II or lower group (p = 0.0096). Notably, a negative correlation existed between preoperatively IAP and hospital stay (r = -0.437, p < 0.001) in cancer resection patients. There was a negative correlation between preoperative serum IAP and the length of ICU stay among cancer patients (r = -0.413, p = 0.008). Among liver cancer patients undergoing surgery, our study identified a significant negative correlation between preoperative serum IAP levels and hospital stay (r = -0.603, p = 0.038). Additionally, when comparing patients based on ICU admission following liver cancer surgeries, those admitted (p = 0.0485). Conclusion: Our study emphasizes the potential of preoperative serum IAP as a valuable biomarker for predicting surgical outcomes, particularly in abdominal and cancer resection surgeries. Higher preoperative serum IAP levels were associated with more favorable outcomes, lower Clavien-Dindo grade, and shorter ICU and hospital stays, while lower IAP levels were linked to higher serum LPS and elevated inflammatory markers, such as IL-6 and CRP. This suggests that serum IAP could serve as a critical prognostic marker, particularly in predicting recovery and complications after abdominal and cancer surgeries. Additionally, while LPS levels did not predict surgical outcomes as strongly as IAP, their significant postoperative reduction highlights their relevance in post-surgical inflammation and gut integrity. Further studies are needed to refine the clinical application of both biomarkers in managing postoperative complications.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Intestinal Alkaline Phosphatase, Lipopolysaccharides, Cancer, Surgical Outcomes
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 1. Juli 2025
• 1. Bericht­erstatter:in: Kühn, Florian