Enhancing intestinal anastomotic healing using butyrate: Systematic review and meta-analysis of experimental animal studies

PLoS One. 2023 Jun 13;18(6):e0286716. doi: 10.1371/journal.pone.0286716. eCollection 2023.

Abstract

Background: Despite advancements in surgical technique and perioperative care, intestinal anastomoses still have a 10-15 per cent risk of leakage, which results in considerable morbidity and/or mortality. Recent animal studies have suggested that administration of butyrate to the anastomotic site results in enhanced anastomotic strength, which may prevent leakage. This systematic review and meta-analysis summarises current evidence concerning the effect of butyrate administration on anastomotic healing and will form a scientific basis for the development of new research into this subject.

Methods: Animal studies on the effect of butyrate-based interventions in models of intestinal anastomotic healing were systematically retrieved from online databases. Bibliographical data, study characteristics and outcome data were extracted, and internal validity of the studies was assessed. Outcomes studied through meta-analysis concerned: anastomotic strength, anastomotic leakage, collagen metabolism and general histologic parameters of wound healing.

Results: A comprehensive search and selection identified 19 relevant studies containing 41 individual comparisons. Design and conduct of most experiments were poorly reported resulting in an unclear risk of bias. Meta-analyses showed that butyrate administration significantly increases anastomotic strength (SMD 1.24, 0.88 to 1.61), collagen synthesis (SMD 1.44, 0.72 to 2.15) and collagen maturation, making anastomoses less prone to leakage in the early postoperative period (OR 0.37, 0.15 to 0.93).

Conclusion: This systematic review and meta-analysis shows that there is potential ground to investigate the use of butyrate in clinical trials to prevent anastomotic leakage in intestinal surgery. However, more research is necessary to define the best application form, dosage and administration route.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anastomosis, Surgical / adverse effects
  • Anastomotic Leak* / prevention & control
  • Animals
  • Animals, Laboratory
  • Butyrates
  • Digestive System Surgical Procedures*
  • Humans
  • Wound Healing

Substances

  • Butyrates

Grants and funding

This work was funded by the ZonMW More Knowledge with Fewer Animals (MKMD) programme (grant number 114024148, awarded to drs A.C.L. Wildeboer) and supported by the Dutch Research Council (NWO) research pro-gramme (Vidi project, number 91719343, awarded to dr. J.P.M. Derikx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.