ArticleScience translational medicine2015
Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02682485 (A Multicenter, Phase II, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial of Serial Endoscopic Surveillance), which is not on this map. Cited by 234 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Phase II, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial of Serial Endoscopic Surveillance (SES) and Direct Topical Antibiotics (DTA) to Define the Role of Microbes in Anastomotic Healing
Who cites it
234 citing papers in PubMed, 6 syntheses or guidelines pooled it, 379 citations in OpenAlex.
- A meta-analysis of the effects of preoperative mechanical intestinal preparation and oral antibiotics on surgical site infection after rectal tumor resection.Updates in surgery · 2026Pooled it
- Gut microbiota and postoperative complications in colorectal surgery and its potential association with intestinal permeability and NLRP6 inflammasome.Frontiers in immunology · 2025Pooled it
- Preoperative combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery.The Cochrane database of systematic reviews · 2023Pooled it
- Role of transanal drainage tubes in preventing anastomotic leakage after low anterior resection: a meta-analysis of randomized controlled trials.Techniques in coloproctology · 2022Pooled it
- Perioperative Probiotics Application for Preventing Postoperative Complications in Patients with Colorectal Cancer: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2022Pooled it
- Matrix metalloproteinase-9 in relation to patients with complications after colorectal surgery: a systematic review.International journal of colorectal disease · 2021Pooled it
- Bowel Stimulation Before Loop Ileostomy Closure Using Probiotics: Study Protocol for a Randomized Controlled Trial at a Single Center.JMIR research protocols · 2026Trial
- The impact of enteral immunonutrition on gut microbiota in colorectal cancer and gastric cancer patients in the preoperative period-preliminary results of randomized clinical trial.Frontiers in immunology · 2025Trial
- Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial.International journal of colorectal disease · 2020Trial
- Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2019Trial
- Multicentre phase II trial of near-infrared imaging in elective colorectal surgery.The British journal of surgery · 2018Trial
- Association Between Surgeons' Consideration of Suspected Biliary Contamination and Reported Antibiotic Duration After Pancreatoduodenectomy: An Exploratory Secondary Analysis of an International Survey.Antibiotics (Basel, Switzerland) · 2026Article
- From Microbiota Correction to Host Protection: A New Therapeutic Target for the Prevention and Treatment of Postoperative Complications.Journal of clinical medicine · 2026Review
- Macrophages in Intestinal Wound Healing: Dichotomous Effects and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Perioperative faecal microbiome dynamics in patients undergoing rectal cancer surgery in the IMARI-trial.BJS open · 2026Article
- Modulation of the gut microbiota as a novel strategy to prevent anastomotic leak after colorectal surgery: Systematic scoping review.Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland · 2026Article
- SparCC co-occurrence networking reveals intracommunity dynamics of the microbiome following colorectal surgery.Microbiology spectrum · 2026Article
- Comparison of Pre- and Postoperative Gut Microbiota Diversity in Patients With Rectal Cancer Undergoing Stoma Creation and Closure.Annals of gastroenterological surgery · 2026Article
- The perioperative microbiome of patients undergoing rectal cancer surgery: A pilot study.Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland · 2026Article
- Anastomotic Leak Following Colorectal Surgery.Clinics in colon and rectal surgery · 2026Review
174 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Even under the most expert care, a properly constructed intestinal anastomosis can fail to heal, resulting in leakage of its contents, peritonitis, and sepsis. The cause of anastomotic leak remains unknown, and its incidence has not changed in decades. We demonstrate that the commensal bacterium Enterococcus faecalis contributes to the pathogenesis of anastomotic leak through its capacity to degrade collagen and to activate tissue matrix metalloproteinase 9 (MMP9) in host intestinal tissues. We demonstrate in rats that leaking anastomotic tissues were colonized by E. faecalis strains that showed an increased collagen-degrading activity and also an increased ability to activate host MMP9, both of which contributed to anastomotic leakage. We demonstrate that the E. faecalis genes gelE and sprE were required for E. faecalis-mediated MMP9 activation. Either elimination of E. faecalis strains through direct topical antibiotics applied to rat intestinal tissues or pharmacological suppression of intestinal MMP9 activation prevented anastomotic leak in rats. In contrast, the standard recommended intravenous antibiotics used in patients undergoing colorectal surgery did not eliminate E. faecalis at anastomotic tissues nor did they prevent leak in our rat model. Finally, we show in humans undergoing colon surgery and treated with the standard recommended intravenous antibiotics that their anastomotic tissues still contained E. faecalis and other bacterial strains with collagen-degrading/MMP9-activating activity. We suggest that intestinal microbes with the capacity to produce collagenases and to activate host metalloproteinase MMP9 may break down collagen in the intestinal tissue contributing to anastomotic leak.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.