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. Here, 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 metalloprotease-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 activity. We suggest that intestinal microbes with the capacity to produce collagenases and to activate host metalloproteinase MMP9 may break down collagen in the gut tissue contributing to anastomotic leak.

Polyphosphate administration may be an alternative approach to prevent anastomotic leak induced by collagenolytic bacteria with the advantage of preserving the intestinal microbiome and its colonization resistance.

These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery.

Assisted partner notification (APN) is recommended by the World Health Organization to notify sexual partners of HIV exposure. Since 2018, APN has been offered in Uganda to Ugandan nationals and refugees. Distinct challenges faced by individuals in refugee settlements may influence APN utilization and effectiveness. To explore APN barriers and facilitators, we extracted index client and sexual partner data from APN registers at 11 health centers providing care to refugees and Ugandan nationals in West Nile Uganda and conducted qualitative interviews with health workers (N = 32). Since APN started, 882 index clients participated in APN identifying 1126 sexual partners. Following notification, 95% (1025/1126) of partners tested for HIV; 22% (230/1025) were diagnosed with HIV with 14% (139/1025) of tested partners newly diagnosed. Fear of stigma and disclosure-related violence limit APN utilization and effectiveness. Prospective research involving index clients and sexual partners is needed to facilitate safe APN optimization in refugee settlements.