Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak

Enterococcus faecalis depletes intestinal collagen, activates the host tissue protease MMP9, and contributes to anastomotic leak. Can our gut microbes prevent wound healing? In a new study, Shogan et al. examined whether the bacterium Enterococcus faecalis, normally present in the intestine, contributes to anastomotic leak, the most feared complication after intestinal surgery. They demonstrated that intestinal E. faecalis can produce a tissue-destroying enzyme that affects the normal healing process by breaking down collagen, a protein that is critical to fully seal the intestine after its removal and reconnection. E. faecalis also activates a host gut enzyme, MMP9, further contributing to anastomotic leak. Finally, the authors demonstrated that the most common antibiotic used in intestinal surgery does not eliminate E. faecalis and thus does not prevent anastomotic leak. 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.