Infliximab Does Not Promote the Presence of Collagenolytic Bacteria in a Mouse Model of Colorectal Anastomosis
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ORIGINAL ARTICLE
Infliximab Does Not Promote the Presence of Collagenolytic Bacteria in a Mouse Model of Colorectal Anastomosis Sara Gaines 1 & Sanjiv Hyoju 1 & Ashley J. Williamson 1 & Jasper B. van Praagh 1,2 & Olga Zaborina 1 & David T. Rubin 1 & John C. Alverdy 1 & Benjamin D. Shogan 1 & Neil Hyman 1 Received: 21 August 2019 / Accepted: 22 November 2019 # 2019 The Society for Surgery of the Alimentary Tract
Abstract Background Previous work from our group has suggested a pivotal role for collagenolytic bacteria in the development of anastomotic complications. Tumor necrosis factor antagonists are a mainstay of treatment for patients with inflammatory bowel disease. The reported impact of these agents on key surgical outcomes such as anastomotic leak has been inconsistent. The objective of this study is to assess the impact of infliximab on the anastomotic microbiome in a mouse model of colon resection. Design BALB/c mice underwent colon resection with primary anastomosis. Mice were randomly assigned to receive either an intraperitoneal dose of saline (control) or 10 mg/kg of infliximab for 8 weeks prior to surgery. On postoperative day 7, the animals were sacrificed. Anastomotic tissues were analyzed by histology with TUNNEL staining as a marker of epithelial apoptosis. In order to assess compositional and functional changes of the local microbiome, anastomotic tissues were further analyzed by 16S rRNA V4 region sequencing and for the presence of collagenolytic strains that may impair anastomotic healing. The main outcome measures were microbiome community structure and the presence of collagenolytic bacteria. Results Infliximab-treated mice demonstrated an increase in epithelial apoptosis, consistent with the expected drug effect. Although infliximab modified the perianastomotic microbiome, no increase in the presence of collagenolytic bacteria was observed. Conclusions Infliximab did not promote the emergence of collagenolytic bacteria or demonstrably impair anastomotic healing in a mouse model of colon resection and anastomosis. Keywords Infliximab . Anastomotic leak . Microbiome
Introduction Anti-tumor necrosis factor (anti-TNF) medications, such as infliximab (IFX), have become a mainstay of treatment for patients with IBD. In fact, the use of biologics in patients with Crohn’s disease doubled from 2009 to 2015, from approximately 20 to 40%.1 Biologic usage in a surgical cohort has been reported to be ~ 60%.2 TNF inhibitors induce apoptosis of monocytes and T cells, thereby inhibiting cytokine release. The impact of this activity on wound healing and surgical complications has been an area of great concern and considerable controversy for many years.
* Neil Hyman [email protected] 1
University of Chicago, Pritzker School of Medicine, 5841 S. Maryland Ave, MC 5095, Chicago, IL 60637, USA
2
University Medical Center Groningen, Groningen, The Netherlands
Observational studies reporting the association of biologic medications with infectious postoperative complications such as anastomotic
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